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Synthesis of glycoconjugates of the lewis Y epitope and uses thereof The present invention provides a method of synthesizing an allyl pentasaccharide having the structure: ##STR1## as well as related oligosaccharide ceramides and other glycoconjugates useful as vaccines for inducing antibodies to epithelial cancer cells in an adjuvant therapy therefor, and in a method for preventing recurrence of epithelial cancer.
Primary Examiner: Fonda; Kathleen K. Attorney, Agent or Firm: White; John P. Cooper & Dunham LLP This invention was made with government support under grants GM-15240-02, GM-16291-01, HL-25848-14 and AI-16943 from the National Institutes of Health. Accordingly, the U.S. Government has certain rights in the invention. This application is a continuation of U.S. Ser. No. 08/506,251, filed Jul. 24, 1995, now U.S. Pat. No. 6,303,120 B1, issued Oct. 16, 2001, which is a continuation-in-part of U.S. Ser. No. 08/430,355, filed Apr. 28, 1995, now U.S. Pat. No. 5,708,163, issued Jan. 13, 1998, which is a continuation-in-part of U.S. Ser. No. 08/213,053, filed Mar. 15, 1994, now U.S. Pat. No. 5,543,505, issued Aug. 6, 1996, the contents of which are hereby incorporated by reference into this application. What is claimed is: 1. A compound having the structure: ##STR99## wherein n is 0, 1, 2, 3, or 4, conjugated to a protein carrier at its allyl group. 2. The compound of claim 1, wherein n is 0 or 2. 3. The compound of claim 1, wherein the conjugation is through a spacer moiety. 4. The compound of claim 3, wherein the spacer moiety is a carbohydrate spacer moiety. 5. The compound of claim 4, wherein the protein carrier is KLH. 6. The compound of claim 3, wherein the protein carrier is KLH. 7. The compound of claim 4, wherein the protein carrier is KLH. 8. A pharmaceutical composition comprising the compound of claim 1, QS21, and a pharmaceutically acceptable carrier. 9. A pharmaceutical composition comprising the compound of claim 5, QS21, and a pharmaceutically acceptable carrier. 10. A pharmaceutical composition comprising the compound of claim 6, QS21, and a pharmaceutically acceptable carrier. 11. A pharmaceutical composition comprising the compound of claim 7, QS21, and a pharmaceutically acceptable carrier. 12. A compound having the structure: ##STR100## conjugated to a protein carrier at its allyl group. 13. The compound of claim 12, wherein the conjugation is through a spacer moiety. 14. The compound of claim 12, wherein the spacer moiety is a carbohydrate spacer moiety. 15. The compound of claim 12, wherein the protein carrier is KLH. 16. The compound of claim 13, wherein the protein carrier is KLH. 17. The compound of claim 14, wherein the protein carrier is KLH. 18. A pharmaceutical composition comprising the compound of claim 12, QS21, and a pharmaceutically acceptable carrier. 19. A pharmaceutical composition comprising the compound of claim 15, QS21, and a pharmaceutically acceptable carrier. 20. A pharmaceutical composition comprising the compound of claim 16, QS21, and a pharmaceutically acceptable carrier. 21. A pharmaceutical composition comprising the compound of claim 17, QS21, and a pharmaceutically acceptable carrier. BACKGROUND OF THE INVENTION Throughout this application, citations for various publications are provided within parentheses in the text. The disclosures of these publications are hereby incorporated in their entirety by reference into this application in order to more fully describe the state of the art to which this invention pertains. The function of carbohydrates as structural materials and as energy storage units in biological systems is well recognized. By contrast, the role of carbohydrates as signaling molecules in the context of biological processes has only recently been appreciated. (M. L. Phillips, E. Nudelman, F. C. A. Gaeta, M. Perez, A. K. Singhal, S. Hakomori, J. C. Paulson, Science, 1990, 250, 1130; M. J. Polley, M. L. Phillips, E. Wagner, E. Nudelman, A. K. Singhal, S. Hakomori, J. C. Paulson, Proc. Natl. Acad. Sci. USA, 1991, 88, 6224: T. Taki, Y. Hirabayashi, H. Ishikawa, S. Kon, Y. Tanaka, M. Matsumoto, J. Biol. Chem., 1986, 261, 3075; Y. Hirabayashi, A. Hyogo, T. Nakao, K. Tsuchiya, Y. Suzuki, M. Matsumoto, K. Kon, S. Ando, ibid., 1990, 265, 8144; 0. Hindsgaul, T. Norberg, J. Le Pendu, R. U. Lemieux, Carbohydr. Res., 1982, 109, 109; U. Spohr, R. U. Lemieux, ibid., 1988, 174, 211) The elucidation of the scope of carbohydrate involvement in mediating cellular interaction is an important area of inquiry in contemporary biomedical research. The carbohydrate molecules, carrying detailed structural information, tend to exist as glycoconjugates (cf. glycoproteins and glycolipids) rather than as free entities. Given the complexities often associated with isolating the conjugates in homogeneous form and the difficulties in retrieving intact carbohydrates from these naturally occurring conjugates, the applicability of synthetic approaches is apparent. (For recent reviews of glycosylation see: Paulsen, H., Angew. Chem. Int. Ed. Engl., 1982, 21, 155; Schmidt, R. R., Angew. Chem. Int. Ed. Engl., 1986, 25, 212; Schmidt, R. R., Comprehensive Organic Synthesis, Vol. 6, Chapter 1(2), Pergamon Press, Oxford, 1991; Schmidt, R. R., Carbohydrates, Synthetic Methods and Applications in Medicinal Chemistry, Part I, Chapter 4, VCH Publishers, Weinheim, N.Y., 1992. For the use of glycals as glycosyl donors in glycoside synthesis, see Lemieux, R. U., Can. J. Chem., 1964, 42, 1417; Lemieux, R. U., Faser-Reid, B., Can. J. Chem., 1965, 43, 1460; Lemieux, R. U., Morgan, A. R., Can. J. Chem., 1965, 43, 2190; Thiem, J., Karl, H., Schwentner, J., Synthesis, 1978, 696; Thiem. J. Ossowski, P., Carbohydr. Chem., 1984, 3, 287; Thiem, J., Prahst, A., Wendt, T. Liebigs Ann. Chem., 1986, 1044; Thiem, J. in Trends in Synthetic Carbohydrate Chemistry, Horton, D., Hawkins, L. D., McGarvvey, G. L., eds., ACS Symposium Series #386, American Chemical Society, Washington, D.C., 1989, Chapter 8.) The carbohydrate domains of the blood group substances contained in both glycoproteins and glycolipids are distributed in erythrocytes, epithelial cells and various secretions. The early focus on these systems centered on their central role in determining blood group specificities. (R. R. Race and R. Sanger, Blood Groups in Man, 6th ed., Blackwell, Oxford, 1975) However, it is recognized that such determinants are broadly implicated in cell adhesion and binding phenomena. (For example, see M. L. Phillips, E. Nudelamn, F. C. A. Gaeta, M. Perez, A. K. Singhal, S. Hakomori, J. C. Paulson, Science, 1990, 250, 1130.) Moreover, ensembles related to the blood group substances in conjugated form are encountered as markers for the onset of various tumors. (K. O. Lloyd, Am. J. Clinical Path., 1987, 87, 129; K. O. Lloyd, Cancer Biol., 1991, 2, 421) Carbohydrate-based tumor antigenic factors might find applications at the diagnostic level, as resources in drug delivery or ideally in immuno-therapy. (Toyokuni, T., Dean, B., Cai, S., Boivin, D., Hakomori, S., and Singhal, A. K., J. Am. Chem Soc., 1994, 116, 395; Dranoff, G., Jaffee, E., Lazenby, A., Golumbek, P., Levitsky, H., Brose, K., Jackson, V., Hamada, H., Paardoll, D., Mulligan, R., Proc. Natl. Acad. Sci. USA, 1993, 90, 3539; Tao, M-H., Levy, R., Nature, 1993, 362, 755; Boon, T., Int. J. Cancer, 1993, 54, 177; Livingston, P. O., Curr. Opin. Immunol., 1992, 4, 624; Hakomori, S., Annu. Rev. Immunol., 1984, 2, 103; K. Shigeta, et al., J. Biol. Chem., 1987, 262, 1358) Livingston et al. (Curr. Opin. Immunol., 1992, 4:624-629) discusses conjugate vaccines with T or sTn covalently attached to keyhole limpet hemocyanin (KLH) and other carriers currently under investigation in a number of laboratories. Vaccines containing synthetic T antigen covalently attached to KLH have resulted in IgM and IgG antibodies and delayed type hypersensitivity reactions against T antigen in the mouse as well as the recovery of mice with established tumors [Livingston et al., Vaccine Res. 1992, 1:99-109; Fung et al., Cancer Res 1990, 50:4308-4314]. Recently, production IgM and IgG antibodies against T antigen in man on administration of these vaccines has also been described [MacLean et al., J. Immunother 1992, 11:292-305]. MacLean's and Livingston's groups (unpublished data) have induced IgM and IgG antibodies against sTn in cancer patients after sTn-KLH vaccinations. Livingston et al. (Curr. Opin. Immunol., 1992, 4:624-629) also indicated that the term immunological adjuvant refers to an agent that increases the specific immune response to antigens. The relative importance of depot effect (i.e. the sequestration of antigen for slow release and for phagocytosis by macrophages and other presenting cells), macrophage activation, and T-cell activation in augmenting immune responses following adjuvant use remains an open question and is probably dependent on the antigen used. Primarily because of the need for adjuvants to augment the immunogenicity of recombinant peptide and purified carbohydrate vaccines against infectious diseases, a number of potent new adjuvants have been prepared and are in various phases of preclinical and clinical testing. These include the following: pleuronic triblock copolymers such as L121 [Hunter et al., Vaccine 1991, 9:250-256], which are known to activate macrophages and facilitate attachment of antigen to lipid-aqueous interfaces; SAF-m, which contains a muramyl dipeptide analog, L121 and squalene [Allison et al., J Immunol Meth 1986, 95:157-168]; Derox which contains a monophosphyryl lipid A analog and mycobacterial cell wall skeletons [Mitchell et al., Cancer Res 1988, 48:5883-5893]; and QS21 which is a purified Quil A saponin fraction [Newman et al., J Immunol 1992, 148:2357]. Of these adjuvants, QS21 is unique in that it is able to induce CTL activity against peptide antigens in addition to the ususal Th-cell activity and antibody responses [Newman et al., J Immunol 1992, 148:2357]. Based on studies comparing the antibody titers and delayed type hypersensitivity responses to a variety of carbohydrate and protein antigens [Livingston et al., Vaccine Res. 1992, 1:99-109; Livingston et al., Vaccine 1992], Livingston et al. selected SAE-m and QS21 as particularly potent adjuvants suitable for study in man. Livingston et al. is conducting Phase I clinical trials with QS21 and SAF-m. The use of synthetic carbohydrate conjugates to elicit antibodies was first demonstrated by Gobel and Avery in 1929. (Goebel, W. F., and Avery, O. T., J. Exp. Med., 1929, 50, 521; Avery, O. T., and Goebel, W. F., J. Exp. Med., 1929, 50, 533.) Carbohydrates were linked to carrier proteins via the benzenediazonium glycosides. Immunization of rabbits with the synthetic antigens generated polyclonal antibodies. Other workers (Allen, P. Z., and Goldstein, I. J., Biochemistry, 1967, 6, 3029; Rude, E., and Delius, M. M., Carbohydr. Res., 1968, 8, 219; Himmelspach, K., et al., Eur. J. Immunol., 1971, 1, 106; Fielder, R. J., et al., J. Immunol., 1970, 105, 265) developed similar techniques for conjugation of carbohydrates to protein carriers. Most of them suffered by introducing an antigenic determinant in the linker itself, resulting in generation of polyclonal antibodies. Kabat (Arakatsu, Y., et al., J. Immunol., 1966, 97, 858), and Gray (Gray, G. R., Arch. Biochem. Biophys. 1974, 163, 426) developed conjugation methods that relied on oxidative or reductive coupling, respectively, of free reducing oligosaccharides. The main disadvantage of these techniques, however, is that the integrity of the reducing end of the oligosaccharide was compromised. In 1975 Lemieux described the use an 8-carbomethoxy-1-octanol linker (Lemieux, R. U., et al., J. Am. Chem. Soc., 1975, 97, 4076) which alleviated the problem of linker antigenicity and left the entire oligosaccharide intact. Equally effective in producing glycoconjugates was the allyl glycoside method described by Bernstein and Hall. (Bernstein, M. A., and Hall, L. D., Carbohydr. Res., 1980, 78, C1.) In this technique the allyl glycoside of the deblocked sugar is ozonized followed by a reductive workup. The resultant aldehyde is then reductively coupled to a protein carrier with sodium cyanoborohydride. In the mid-70's and early 80's Lemieux and his collaborators made contributions to antibody production stimulated by synthetic glycoconjugates (Lemieux, R. U., et al., J. Am. Chem. Soc., 1975, 97, 4076) and to conformational issues (Lemieux, R. U., et al., Can. J. Chem., 1979, 58, 631; Spohr, U., et al., Can. J. Chem., 1985, 64, 2644; Vandonselaar, M., et al., J. Biol. Chem., 1987, 262, 10848) important in the interactions of the blood group determinants (and analogues thereof) with the carbohydrate binding proteins known as lectins. More recently, workers at Bristol-Meyers Squibb reported the X-ray crystal structure of the Lewis.sup.y epitope complexed with the antibody BR96. (Jeffrey, P. D., et al., Nature Structural Biol., 1995, 2, 466.) Two main components appear to govern recognition between carbohydrates and most antibodies. The first is multiple hydrogen bonding between the sugar hydroxyls and the amino acid residues of Asp, Asn, Glu, Gln, and Arg. The second major interaction is stacking between the sugar-ring faces and aromatic side chains, which occurs most frequently with tryptophan. In the complex with BR96 the most significant interactions involve the latter; additional hydrogen bonding occurs between the sugar hydroxyls and the indole nitrogens. Most antibody binding sites can support about 6 linear carbohydrate residues in a groove or cavity shaped binding site. Glycoconjugates would be used, ideally, in direct immunotherapy or the monoclonal antibodies generated from vaccinations could be used to specifically target known chemotherapeutic agents to tumor sites. The immune response to carbohydrates is generally not strong, resulting mainly in production of IgM type antibodies. IgM antibodies are capable of complement fixation. Complement is a family of enzymes that can lyse cells to which antibodies are bound. The response to carbohydrate antigens normally does not enlist the use of T-cells which would aid in the body's rejection of the tumor. While the probability of complete tumor rejection as a result of vaccination with a conjugate is unlikely, such treatments will boost immune surveillance and recurrence of new tumor colonies can be reduced. (Dennis, J., Oxford Glycosystems Glyconews Second, 1992; Lloyd, K. O., in Specific Immunotherapy of Cancer with Vaccines, 1993, New York Academy of Sciences, 50-58.) Toyokuni and Singhal have described a synthetic glycoconjugate (Toyokuni, T., et al., J. Am. Chem. Soc., 1994, 116, 395) that stimulated a measurable IgG titer, a result which is significant since an IgG response is generally associated with enlistment of helper T cells. The use of immunoconjugates has shown promise in the reduction of large tumor masses. The workers at Bristol-Meyers Squibb (Trail, P. A., et al., Science, 1993, 261, 212) have described the attachment of the known chemotherapeutic drug doxorubicin to the antibody BR96. BR96 is an anti-Lewis.sup.y antibody which has been shown to bind to human breast, lung and colon carcinomas. Athymic mice that have had human cancers (L2987-lung, RCA-colon, and MCF7-breast carcinomas) xenografted subcutaneously were treated with the drug-antibody conjugate (BR96-DOX). The result was complete regression of the tumor mass in 78% of the mice treated. BR96 is efficiently internalized by cellular lysosomes and endosomes following attachment to the cell surface. The change in pH upon internalization results in cleavage of the labile hydrazone thereby targeting the drug specifically to the desired site. Many of the blood group determinant structures can also occur in normal tissues. Antigen expression in normal cells and cancer cells can have subtle distributional differences. In the case of Le.sup.y, (which does appear in normal tissues) the expression of the determinant in tumor cells tends to be in the form of mucins which are secreted. Mucins are glycoproteins with a high content of the amino acids serine and threonine. It is through the hydroxyl functionality of these amino acids that Lewis.sup.y is linked. Thus, in terms of generating competent antibodies against tumor cells expressing the Le.sup.y antigen it is important that the antibody recognize the mucin structure. Structurally, the blood group determinants fall into two basic categories known as type I and type II. Type I is characterized by a backbone comprised of a galactose 1-3b linked to N-acetyl glucosamine while type II contains, instead, a 1-4b linkage between the same building blocks (cf. N-acetyl lactosamine). The position and extent of a-fucosylation of these backbone structures gives rise to the Lewis-type and H-type specificities. Thus, monofucosylation at the C.sub.4 -hydroxyl of the N-acetyl glucosamine (Type I series) constitutes the Le.sup.a type, whereas fucosylation of the C.sub.3 -hydroxyl of this sugar (Type II series) constitutes the Le.sup.x determinant. Additional fucosylation of Le.sup.a and Le.sup.x types at the C.sub.2' -hydroxyl of the galactose sector specifies the Le.sup.b and Le.sup.y types, respectively. The Le.sup.y determinant is expressed in human colonic and liver adenocarcinomas. (Levery, S. B., et al., Carbohydr. Res., 1986, 151, 311; Kim, Y. S., J. Cellular Biochem. Suppl., 16G 1992, 96; Kaizu, T., et al., J. Biol. Chem., 1986, 261, 11254; Levery, S. B., et al., Carbohydr. Res. 1986, 151, 311; Hakomori, S., et al., J. Biol. Chem., 1984, 259, 4672; Fukushi, Y., et al., ibid., 1984, 259, 4681; Fukushi, Y., et al., ibid., 1984, 259, 10511.) The presence of an a-monofucosyl branch, solely at the C.sub.2' -hydroxyl in the galactose moiety in the backbone, constitutes the H-type specifity (Types I and II). Further permutation of the H-types by substitution of a-linked galactose or a-linked N-acetylgalactosamine at its C.sub.3' -hydroxyl group provides the molecular basis of the familiar serological blood group classifications A, B, and O. (Lowe, J. B., The Molecular Basis of Blood Diseases, Stamatoyannopoulos, et. al., eds., W. B. Saunders Co., Philadelphia, Pa., 1994, 293.) Several issues merit consideration in contemplating the synthesis of such blood group substances and their neoglycoconjugates. For purposes of synthetic economy it would be helpful to gain relief from elaborate protecting group manipulations common to traditional syntheses of complex branched carbohydrates. Another issue involves fashioning a determinant linked to a protein carrier. It is only in the context of such conjugates that the determinants are able to galvanize B-cell response and complement fixation. In crafting such constructs, it is beneficial to incorporate appropriate spacer units between the carbohydrate determinant and the carrier. (Stroud, M. R., et al., Biochemistry, 1994, 33, 10672; Yuen, C.-T., et al., J. Biochem., 1994, 269, 1595; Stroud, M. R., et al., J. Biol. Chem., 1991, 266, 8439.) The present invention provides new strategies and protocols for oligosaccharide synthesis. The object is to simplify such constructions such that relatively complex domains can be assembled with high stereo-specifity. Major advances in glycoconjugate synthesis require the attainment of a high degree of convergence and relief from the burdens associated with the manipulation of blocking groups. Another requirement is that of delivering the carbohydrate determinant with appropriate provision for conjugation to carrier proteins or lipids. (Bernstein, M. A., and Hall, L. D., Carbohydr. Res., 1980, 78, Cl; Lemieux, R. U., Chem. Soc. Rev., 1978, 7, 423; R. U. Lemieux, et al., J. Am. Chem. Soc., 1975, 97, 4076) This is a critical condition if the synthetically derived carbohydrates are to be incorporated into carriers suitable for biological application. Antigens which are selective or ideally specific for cancer cells could prove useful in fostering active immunity. (Hakomori, S., Cancer Res., 1985, 45, 2405-2414; Feizi, T., Cancer Surveys, 1985, 4, 245-269) Novel carbohydrate patterns are often presented by transformed cells as either cell surface glycoproteins or as membrane-anchored glycolipids. In principle, well chosen synthetic glycoconjugates which stimulate antibody production could confer active immunity against cancers which present equivalent structure types on their cell surfaces. (Dennis, J., Oxford Glycosystems Glyconews Second, 1992; Lloyd, K. O., in Specific Immunotherapy of Cancer with Vaccines, 1993, New York Academy of Sciences pp. 50-58) Chances for successful therapy improve with increasing restriction of the antigen to the target cell. A glycosphingolipid was isolated by Hakomori and collaborators from the breast cancer cell line MCF-7 and immunocharacterized by monoclonal antibody MBr1. (Bremer, E. G., et al., J. Biol. Chem., 1984, 259, 14773-14777; Menard, S., et al., Cancer Res., 1983, 43, 1295-1300) The novel glycosphingolipid structure 1b (FIG. 8) was proposed for this breast tumor-associated antigen on the basis of methylation and enzymatic degradation protocols. A .sup.1 H NMR spectrum consistent with but not definitive for the proposed structure was obtained from trace amounts of isolated antigen. While individual sectors of the proposed structure were not unknown, the full structure was first described based on studies on the breast cancer line. It should be noted that MBr1 also binds to normal human mammary gland tissue and ovarian cancer cell lines. Therefore,1b as a total entity is likely not restricted to the transformed breast cells. Alternatively, smaller subsections of 1b are adequate for antibody recognition and binding. (The synthesis of the DEF fragment of 1b has been reported, and has been shown to bind to MBr1: Lay, L., et al., Helv. Chim. Acta, 1994, 77, 509-514.) The compounds prepared by processes described herein are antigens useful in adjuvant therapies as vaccines capable of inducing antibodies immunoreactive with epithelial carcinomas, for example, human colon, lung and ovarian tumors. Such adjuvant therapies have potential to reduce the rate of recurrence of cancer and increase survival rates after surgery. Clinical trials on 122 patents surgically treated for AJCC stage III melanoma who were treated with vaccines prepared from melanoma differentiation antigen GM2 (another tumor antigen which like MBr1 is a cell surface carbohydrate) demonstrated in patients (lacking the antibody prior to immunization) a highly significant increase in disease-free interval (P. O. Livingston, et al., J. Clin Oncol., 12, 1036 (1994)). The present invention provides a method of synthesizing Le.sup.y -related antigens as well as artificial protein-conjugates of the oligosaccharide which might be more immunogenic than the smaller glycolipid. The antigen contains a novel array of features including the .alpha.-linkage between the B and the C entities, as well as the .beta.-linked ring D gal-NAc residue. (For the synthesis of a related structure (SSEA-3) which lacks the fucose residue see: Nunomura, S.; Ogawa, T., Tetrahedron Lett., 1988, 29, 5681-5684.) The present invention also provides a total synthesis of 1b, rigorous proof that the Hakomori antigen does, in fact, correspond to 1b and the synthesis of a bioconjugatable version of 1b. The conciseness of the synthesis reflects the efficiency of glycal assembly methods augmented by a powerful method for sulfonamidoglycosylation (see, e.g., the transformation of 14b-15b, FIG. 10). BRIEF DESCRIPTION OF THE FIGURES FIG. 1 shows glycal assembly leading to neoglycoproteins. FIG. 2 shows the synthesis of 4a. Reagents: a) TBDPSCL, imidazole/DMF 84%; b) carbonyldiimidazole, cat. imidazole, THF (65%) c) 5a, di-tert-butylpyridine, AgClO.sub.4, SnCl.sub.2, ether (51%); PhSO.sub.2 NH.sub.2, 1(sym-coll).sub.2 ClO.sub.4 (94%). FIG. 3 shows the synthesis of 8a. Reagents: a) 9a, AgBF.sub.4, 4A mol. sieves, THF (75%); b) i. TBAF, THF; ii. Na/NH.sub.3 ; iii Ac.sub.2 O, pyr. c) i. 3,3-dimethioxirane; allyl alcohol, ZnCl.sub.2 (72%); ii. NaOMe, MeOH (quant.). FIG. 4 shows a strategy for the solid-phase of oligosaccharides using the glycal assembly method. FIG. 5 shows the application of the solid-support method to the assembly of 1,2-branching patterns of complex carbohydrates. FIG. 6 shows the synthesis of a tetrasaccharide having H-type 2 blood group specificity. Reagents: (a) 1. 3,3-dimethyldioxirane, CH.sub.2 Cl.sub.2 ; 2. 8, ZnCl.sub.2, THF; (b) 10, Sn(OTf).sub.2, di-tert-butylpyridine, THF; (c) TBAF, AcOH, THF; (d) TIPSCl, imidazole, DMF; (e) I(coll).sub.2 ClO.sub.4, PhSO.sub.2 NH.sub.2, CH.sub.2 Cl.sub.2 ; (f) 15, AgBF.sub.4, 4A M.S., THF; (g) 1. TBAF, AcOH, THF; 2. Na/NH.sub.3 ; 3. Ac.sub.2 O, pyridine. FIGS. 7a and 7b show the synthesis of a Le.sup.b hexa-saccharide in bioconjugatable form. Reagents: (a) 1. 3,3-dimethyldioxirane, CH.sub.2 Cl.sub.2 ; 2. 19, ZnCl.sub.2, THF; (b) 10, Sn(OTf).sub.2 di-tert-butylpyridine, THF; (c) TBAF, AcOH, THF; (d) TIPSCl, imidazole, DMF; (e) I(coll).sub.2 ClO.sub.4, PhSO.sub.2 NH.sub.2, CH.sub.2 Cl.sub.2 ; (f) 24, AgBF.sub.4, 4A M.S., THF; (g) 1. TBAF, AcOH, THF; 2. Na/NH.sub.3 ; 3. Ac.sub.2 O, pyridine; (h) 1. 3,3-dimethyldioxirane, CH.sub.2 Cl.sub.2 ; 2. allyl alcohol, ZnCl.sub.2 ; 3. NaOMe, MeOH. FIG. 8 shows the structure of the MBr1 antigen and a reaction pathway to a trisaccharide intermediate. Reagents: a. n-Bu.sub.2 SnO, PMBCl, TBABr, PhH, 70%; b. NaH, BnBr, DMF, 95%; c. (i) 3.3-dimethyldioxirane, CH.sub.2 Cl.sub.2 ; (ii) TBAF, THF; (iii) NaH, BnBr, DMF, 40% (three steps); d. NaH, BnBr, DMF, 80%; e. (i) TBAF, THF; (ii) NaOMe, MeOH, 93% (two steps); f. (n-Bu.sub.3 Sn).sub.2 O, BnBr, TBABr, PhH, 90%;g. SnCl.sub.2, AgClO.sub.4, 2,6-di-butylpyridine, 4 .ANG. mol. sieves, Et.sub.2 O, 40% .alpha. (4.5:1 .alpha.:B); h. DDQ, CH.sub.2 CI.sub.2, H.sub.2 O, 84%. FIG. 9 shows a reaction pathway to a trisaccharide intermediate. Reagents: a. (i) 3,3-dimethyldioxirane, CH.sub.2 CI.sub.2 ; (ii) 10a, ZnCl.sub.2, THF, 87%; b. SnCl.sub.2, AgClO.sub.4, Et.sub.2 O, 47%; c. I(coll).sub.2 ClO.sub.4, PhSO.sub.2 NH.sub.2, 4 .ANG. mol. sieves, 47%. FIG. 10(a) shows a reaction pathway to the hexasaccharide MBr1 antigen. Reagents: a. EtSH, LiHMDS, DMF, 75%. B. 8b (0.5 equiv), MeOTf, 4 .ANG. Mol. sieves, 70-85% B, (10:1 B .alpha.); c. (i) 3,3-dimethyldioxirane, CH.sub.2 Cl.sub.2 (ii) 17b (5 equiv), Zn(OTf).sub.2, 20%; d. Ac.sub.2 O, Et.sub.3 N, DMAP, CH.sub.2 Cl.sub.2 95%; e. Lindlar's cat., H.sub.2 palmitic anhydride, EtOAc, 90%; f. (i) TBAF, THF; (ii) NaOMe, MeOH, 94%; g. (i) Na, NH.sub.3, THF; (ii) Ac.sub.2 O, Et.sub.3 N, DMAP, CH.sub.2 Cl.sub.2, 80% h. NaOMe, MeOH, quant. FIG. 10(b) shows a reaction pathway to the allyl glycoside. Reagents: a. TBAF, THF, 94%; b. (i) Na, NH.sub.3, THF; (ii) Ac.sub.2 O, Et.sub.3 N, DMAP, THF, DMF, 85%; c. (i) 3,3-dimethyldioxirane, CH.sub.2 Cl.sub.2, (ii) allyl alcohol, 65% (+29% of .alpha.-manno isomer); d. NaOMe, MeOH, quant. FIG. 11 shows a reaction pathway to intermediates for preparing the hexasaccharide antigen MBr1. FIG. 12 shows a reaction pathway to the hexasaccharide antigen MBr1 by a 4+2 synthetic approach. FIG. 13(a) shows the proposed mode of action for inflammatory response. FIG. 13(b) shows the structure of SLe.sup.x. FIG. 13(c) shows the structure of sulfated E-selectin ligands. FIG. 14(a) shows a reaction pathway to prepare the Lubineau sulfated Le.sup.a. FIG. 14(b) shows a reaction pathway to prepare the Nicolau sulfated Le.sup.a. FIG. 15(a) shows compounds 17d, 18d and sulfated Le.sup.a 19d. FIG. 15(b) shows the preparation of sulfated Le.sup.x glycal 21d. FIG. 15(c) shows the preparation of trisaccharide intermediates 26d and 27d. FIG. 16(a) shows the preparation of disaccharide intermediates 30d and 31d. FIG. 16(b) shows the preparation of trisaccharide Le.sup.a glycal 32d. FIG. 16(c) shows the preparation of trisaccharide intermediate 35d. FIG. 17 shows the preparation of sulfated trisaccharide 19d. FIG. 18(a) shows the preparation of TIPS- and TBDPS-protected tetrasaccharides 22c, 23c and 24c. FIG. 18(b) shows the preparation of TBDPS-protected tetrasaccharide intermediate 25c. FIG. 18(c) shows the preparation of TBDPS-protected tetrasaccharide ceramide intermediate 28c. FIG. 18(d) shows a model reduction reaction to prepare tetrasaccharide ceramides. FIG. 19(a) shows a reduction reaction to prepare tetrasaccharide ceramide intermediate 31c. FIG. 19(b) shows a reaction pathway to prepare tetrasaccharide ceramide 32c. FIG. 20(a) shows the reactivity of compound 17c with .alpha.Le.sup.y (s193) and .alpha.Le.sup.b (T218) control. FIG. 20(b) shows the the enzyme-linked immunosorbant assay used to measure antibody titer. FIG. 21 shows in panels A, B and C the measured titers of total antibody Ig, IgM and IgG type antibodies, respectively, in five mice immunized with conjugate 17c; in panels D, E and F controls where mice were immunized with BSA carrier alone. FIG. 21 shows in panels G, H and I the measured titer of Ig, IgM and IgG type antibodies with the Le.sup.y mucin structure as the test antigen, respectively, mice immunized with conjugate 17c; in panels J, K and L show results of immunization with ceramide conjugate 32b. FIG. 22(a) shows the preparation of tetrasaccharide intermediate 11c. FIG. 22(b) shows the preparation of O-allyl pentasaccharide 15c. FIG. 22(c) shows the preparation of a Le.sup.y -BSA glycoconjugate 17c by reductive amination of petasaccharide aldehyde intermediate 16c. FIG. 23(a) shows the preparation of protected hexasaccharide glycal 19c. FIG. 23(b) shows three methods of elaborating tetrasaccharide iodosulfonamide 11c. SUMMARY OF THE INVENTION The present invention provides a method of synthesizing an allyl pentasaccharide having the structure: ##STR2## The present invention also provides a method of synthesizing a ceramide having the structure: ##STR3## The present invention further provides a compound having the structure: ##STR4## wherein R is H, substituted or unsubstituted alkyl, aryl or allyl, or an amino acyl moiety, an amino acyl residue of a peptide, an amino acyl residue of a protein, which amino acyl moiety or residue bears an .omega.-amino group or an .omega.-(C.dbd.O)-- group, which group is linked to O via a poly-methylene chain having the structure --(CH.sub.2).sub.r --, where r is an integer between about 1 and 9, or a moiety having the structure: ##STR5## and wherein k, m and n are independently 0, 1, 2 or 3. The present invention also provides a compound having the structure: ##STR6## wherein n is 0, 1, 2, 3 or 4. The present invention also provides a compound having the structure: ##STR7## In addition, the present invention provides a method of inducing antibodies in a subject, wherein the antibodies are capable of specifically binding with epithelial tumor cells, which comprises administering to the subject an amount of a compound which contains a Le.sup.y tetrasaccharide determinant having the structure: ##STR8## effective to induce the antibodies. The present invention provides a method of preventing recurrence of epithelial cancer in a subject which comprises vaccinating the subject with a compound which contains a Le.sup.y tetrasaccharide determinant having the structure: ##STR9## effective to induce the antibodies. DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method of synthesizing an allyl pentasaccharide having the structure: ##STR10## which comprises: (a)(i) de-silylating a compound having the structure: ##STR11## with R.sup.1 R.sup.2 R.sup.3 R.sup.4 NF wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently a linear or branched chain alkyl, aralkyl or aryl, to form an N-sulfonamide pentasaccharide; (ii) cleaving the N-sulfonamide pentasaccharide formed in step (a)(i) to form a deprotected pentasaccharide; and (iii) acetylating the deprotected pentasaccharide formed in step (b)(ii) to form a peracetate having the structure: ##STR12## (b)(i) treating the peracetate formed in step (a)(iii) with an epoxidizing agent to form an epoxide peracetate; (ii) reacting the epoxide peracetate formed in step (b)(i) with allyl alcohol to form an allylglycoside peracetate; and (iii) cleaving the allylglycoside peracetate with an alkoxide salt to form the allyl pentasaccharide. In one embodiment, the present invention provides the method wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 in step (a)(i) are n-butyl. In another embodiment, the present invention provides a method wherein the cleaving step (a)(ii) is performed with Na/NH.sub.3. In another embodiment, the present invention provides a method wherein the epoxidizing agent of step (b)(i) is 3,3-dimethyldioxirane. In another embodiment, the present invention provides a method wherein the alkoxide salt of step (b)(iii) is NaOMe. Step (a)(i) may be carried out using a fluoride salt such as tetra-n-butylammonium fluoride in a suitable nonaqueous dipolar solvent, such as THF. Cleaving step (a)(ii) may be effected using a reducing metal in liquid ammonia with a proton donor such as methanol or ethanol. Peracetylation step (a)(iii) is performed using acetyl chloride or acetic anydride in the presence of an organic base such as pyridine. Epoxidation step (b)(i) is effected using an epoxidizing agent such as peracetic acid, m-chloroperbenzoic acid or trifluoroacetic acid, but preferably with 3,3-dimethyldioxirane. Ring-opening step (b)(ii) is carried out-with allyl alcohol in the presence of a Lewis acid catalyst such as ZnCl.sub.2. Saponification step (b)(iii) is effected using a metal alkoxide such as sodium, lithium or potassium methoxide or ethoxide in the presence of the corresponding alcohol. The present invention also provides a method of synthesizing a ceramide having the structure: ##STR13## which comprises: (a) treating a compound having the structure: ##STR14## with aqueous silver(I) followed by reacting with diethylaminosulfur trifluoride to form a compound having the structure: ##STR15## (b) treating the compound formed in step (a) with azidosphingosine to form a compound having the structure: ##STR16## (c) reducing the compound formed in step (b) to form a compound having the structure: ##STR17## and (d)(i) de-silylating the compound formed in step (c) with R.sup.1 R.sup.2 R.sup.3 R.sup.4 NF wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently a linear or branched chain alkyl, aralkyl or aryl; (ii) reductively cleaving the compound formed in step (d)(i) to form a polyalcohol tetrasaccharide; (iii) peracetylating the polyalcohol tetrasaccharide to form a peracetate tetrasaccharide; and (iv) saponifying the peracetate tetrasaccharide with a metal alkoxide to form the ceramide. In one embodiment, the present invention provides a method wherein silver(I) in step (a) is silver carbonate. In another embodiment, the present invention provides a method wherein step (b) is performed in the presence of zirconocene dichloride and silver triflate. In another embodiment, the present invention provides a method wherein the reducing step (c) is performed using hydrogen gas and palmitic anhydride in the presence of Lindlar's catalyst. In yet another embodiment, the present invention provides a method wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 in step (d)(i) are n-butyl and step (d)(ii) is performed using Na/NH.sub.3. Treating step (a) is effected using a silver salt, such as silver carbonate, in the presence of a nonnucleophilic base, such as triethylamine, in a mixed aqueous and dipolar solvent such as THF. After aqueous solvents are removed, the mixture is treated in situ at low temperatures, between -60.degree. and 0.degree., preferably at about -30.degree., with diethylaminosulfur trifluoride (DAST) under suitable conditions. Coupling step (b) is carried out using a mixed metal system such as Cp.sub.2 ZrCl.sub.2 and silver triflate in an organic solvent such as dichloromethane. Reducing step (c) is effected using a noble metal catalyst such as Lindlar's catalyst and a hydrogen atmosphere at ambient to 100 psi. De-silylating step (d)(i) may be carried out using a fluoride salt such as tetra-n-butylammonium fluoride in a suitable nonaqueous dipolar solvent, such as THF. Cleaving step (d)(ii) may be effected using a reducing metal in liquid ammonia with a proton donor such as methanol or ethanol. Peracetylation step (d)(iii) is performed using acetyl chloride or acetic anydride in the presence of an organic base such as pyridine. Saponification step (d)(iv) is effected using a metal alkoxide such as sodium, lithium or potassium methoxide or ethoxide in the presence of the corresponding alcohol. The present invention provides a compound having the structure: ##STR18## wherein R is H, substituted or unsubstituted alkyl, aryl or allyl, or an amino acyl moiety, an amino acyl residue of a peptide, an amino acyl residue of a protein, which amino acyl moiety or residue bears an .omega.-amino group or an .omega.-(C.dbd.O)-- group, which group is linked to O via a poly-methylene chain having the structure --(CH.sub.2).sub.r --, where r is an integer between about 1 and 9, or a moiety having the structure: ##STR19## and wherein k, m and n are independently 0, 1, 2 or 3. In one embodiment, the present invention further provides a compound having the structure: ##STR20## wherein k, m and n are independently 0, 1, 2 or 3. In another embodiment, the present invention provides a compound having the structure: ##STR21## The present invention also provides a compound having the structure: ##STR22## wherein n is 0, 1, 2, 3 or 4. In one embodiment, the present invention provides a compound wherein n is 1. In another embodiment, the present invention provides a compound wherein n is 2. In general, each O-allyl Le.sup.y containing oligosaccharide may be linked to a carrier protein by a two-step process. Ozonolysis affords an aldehyde which is then reductively aminated by the free surface .epsilon.-amines of the carrier protein, using a reducing agent such as sodium cyano-borobydride. The product is a Le.sup.y -carrier protein adduct useful for inducing antibodies as disclosed herein. The present invention also provides a compound having the structure: ##STR23## The present invention provides several therapeutic uses for the compounds disclosed herein. Accordingly, the present invention provides a method of inducing antibodies in a subject, wherein the antibodies are capable of specifically binding with epithelial tumor cells, which comprises administering to the subject an amount of a compound which contains a Le.sup.y tetrasaccharide determinant having the structure: ##STR24## effective to induce the antibodies. In one embodiment, the present invention provides a method wherein the compound is bound to a suitable carrier protein. In a certain embodiment, the present invention provides a method wherein the carrier protein is bovine serum albumin, polylysine, or KLH. In another certain embodiment, the present invention provides a method which further comprises coadministering an immunological adjuvant. In another embodiment, the present invention provides a method wherein the adjuvant is bacteria or liposomes. Specifically, the invention provides a method wherein the adjuvant is Salmonella Minnesota cells, bacille Calmette-Guerin, or QS21. In various embodiments, the present invention may be practiced using any of the compounds disclosed hereinabove. In a further embodiment, the present invention provides a method wherein the subject is in clinical remission or, where the subject has been treated by surgery, has limited unresected disease. The present invention also provides a method of inducing antibodies in a subject, wherein the antibodies are capable of specifically binding with colon tumor cells, which comprises administering to the subject an amount of a compound which contains a Le.sup.y tetrasaccharide determinant having the structure: ##STR25## effective to induce the antibodies. In one embodiment, the present invention provides a method wherein the compound is bound to a suitable carrier protein. In a certain embodiment, the present invention provides a method wherein the carrier protein is bovine serum albumin, polylysine, or KLH. In another certain embodiment, the present invention provides a method which further comprises coadministering an immunological adjuvant. In another embodiment, the present invention provides a method wherein the adjuvant is bacteria or liposomes. Specifically, the invention provides a method wherein the adjuvant is Salmonella minnesota cells, bacille Calmette-Guerin, or QS21. In various embodiments, the present invention may be practiced using any of the compounds disclosed hereinabove. In a further embodiment, the present invention provides a method wherein the subject is in clinical remission or, where the subject has been treated by surgery, has limited unresected disease. The present further provides a method of inducing antibodies in a subject, wherein the antibodies are capable of specifically binding with ovarian tumor cells, which comprises administering to the subject an amount of a compound which contains a Le.sup.y tetrasaccharide determinant having the structure: ##STR26## effective to induce the antibodies. In one embodiment, the present invention provides a method wherein the compound is bound to a suitable carrier protein. In a certain embodiment, the present invention provides a method wherein the carrier protein is bovine serum albumin, polylysine, or KLH. In another certain embodiment, the present invention provides a method which further comprises coadministering an immunological adjuvant. In another embodiment, the present invention provides a method wherein the adjuvant is bacteria or liposomes. Specifically, the invention provides a method wherein the adjuvant is Salmonella minnesota cells, bacille Calmette-Guerin, or QS21. In various embodiments, the present invention may be practiced using any of the compounds disclosed hereinabove. In a further embodiment, the present invention provides a method wherein the subject is in clinical remission or, where the subject has been treated by surgery, has limited unresected disease. The present invention provides a method of preventing recurrence of epithelial cancer in a subject which comprises vaccinating the subject with a compound which contains a Le.sup.y tetrasaccharide determinant having the structure: ##STR27## effective to induce the antibodies. In particular, the present invention provides a method of preventing recurrence of colon cancer in a subject which comprises vaccinating the subject with a compound which contains a Le.sup.y tetrasaccharide determinant having the structure: ##STR28## effective to induce the antibodies. In various embodiments, the present invention may be practiced using any of the compounds disclosed hereinabove. The present invention also provides a method of preventing recurrence of ovarian cancer in a subject which comprises vaccinating the subject with a compound which contains a Le.sup.y tetrasaccharide determinant having the structure: ##STR29## effective to induce the antibodies. In various embodiments, the present invention provides a method of treating epithelial tumors, including colon, lung, ovarian, and prostate, wherein the compound is bound to a suitable carrier protein. In various embodiments, the present invention provides a method wherein the carrier protein is bovine serum albumin, polylysine, or KLH. In other embodiments, the present invention provides a method which further comprises coadministering an immunological adjuvant. In certain embodiments, the present invention provides a method wherein the adjuvant is bacteria or liposomes. In specific embodiments, the present invention provides a method wherein the adjuvant is Salmonella minnesota cells, bacille Calmette-Guerin, or QS21. In certain embodiments, the present invention may be practiced using any of the compounds disclosed hereinabove. The present invention provides a compound having the structure: ##STR30## wherein A is selected from the group consisting of (i) an amino acid bearing an .omega.-amino group or an .omega.-(C.dbd.O)-- group, (ii) an amino acid residue of a peptide, which residue bears an .omega.-amino group or an .omega.-(C.dbd.O)-- group, and (iii) an amino acid residue of a protein, which residue bears an .omega.-amino group or an .omega.-(C.dbd.O)-- group; wherein R.sub.1 is H, OH, NH.sub.2 or NHR.sub.4, where R.sub.4 is SO.sub.2 Ph, a linear or branched chain alkyl or acyl group, or an aryl group; wherein M has the structure: ##STR31## wherein n is an integer from 0 to 18, and where n is greater than 1, each M is independently the same or different; wherein p is either 0 or 1; wherein R.sub.2, R.sub.3, R.sub.5 and R.sub.6 are independently the same or different and are H or OH, with the proviso that geminal R.sub.2 and R.sub.3 are not both OH, and geminal R.sub.5 and R.sub.6 are not both OH; wherein each wavy line between a carbon atom and an oxygen atom denotes an R or S configuration at the carbon atom; wherein X and Y are independently the same or different and are H.sub.2 or O; and wherein k is an integer greater than or equal to 1, with the proviso that when A is an amino acid bearing an .omega.-amino group or an .omega.-(C.dbd.O)-- group, k is equal to 1. In one embodiment, the present invention provides the compound disclosed hereinabove wherein A is lysine or a lysine residue. In another embodiment, the present invention provides the compound disclosed hereinabove wherein A is glutamic acid or a glutamic acid residue. In another embodiment, the present invention provides the compound disclosed hereinabove wherein A is aspartic acid or an aspartic acid residue. The invention also provides the compound disclosed hereinabove wherein A is an amino acid residue of a globular protein. In one embodiment, the invention provides the compound wherein the globular protein is selected from the group consisting of bovine serum albumin and human serum albumin. In one embodiment, the invention provides the compound disclosed hereinabove wherein k is 1. In another embodiment, the invention provides the compound disclosed hereinabove wherein n and p are both equal to 0. The invention provides a compound having the structure: ##STR32## wherein R.sub.1 is H, OH, NH.sub.2 or NHR.sub.4 where R.sub.4 is SO.sub.2 Ph, a linear or branched chain alkyl or acyl group, or an aryl group; wherein M has the structure: ##STR33## wherein n is an integer from 0 to 18, and where n is greater than 1, each M is independently the same or different; wherein R.sub.2, R.sub.3, R.sub.5 and R.sub.6 are independently the same or different and are H or OH, with the proviso that geminal R.sub.2 and R.sub.3 are not both OH, and geminal R.sub.5 and R.sub.6 are not both OH; wherein each wavy line between a carbon atom and an oxygen atom denotes an R or S configuration at the carbon atom; and wherein R.sub.7 is a substituted or unsubstituted allyl group. The invention also provides a compound having the structure: ##STR34## wherein n is an integer from 1 to 18; wherein R is H or a linear or branched chain acyl group; wherein R.sub.1 is H, OH, NH.sub.2 or NHR.sub.4, where R.sub.4 is SO.sub.2 Ph, a linear or branched chain alkyl or acyl group, or an aryl group; and wherein R.sub.2 is a substituted or unsubstituted allyl group. In one embodiment, the invention provides the compound wherein n is 1. The invention further provides a compound having the structure: ##STR35## wherein R is H or a linear or branched chain acyl group; wherein R.sub.1 is H, OH, NH.sub.2 or NHR.sub.4, where R.sub.4 is SO.sub.2 Ph, a linear or branched chain alkyl or acyl group, or an aryl group; and wherein R.sub.2 is a substituted or unsubstituted allyl group. The invention also provides a compound having the structure: ##STR36## wherein R is H or a linear or branched chain acyl group; wherein R.sub.1 is H, OH, NH.sub.2 or NHR.sub.4, where R.sub.4 is SO.sub.2 Ph, a linear or branched chain alkyl or acyl group, or an aryl group; wherein R.sub.2 is a substituted or unsubstituted allyl group; and wherein n is an integer from 1 to 18. In one embodiment, the invention provides the compound wherein n is 1. The invention also provides a compound having the structure: ##STR37## wherein R is H or a linear or branched chain acyl group. The invention also provides a process for synthesizing a compound having the structure: ##STR38## wherein R is a substituted or substituted allyl group, which comprises the steps of (a) synthesizing a compound having the structure: ##STR39## wherein R is a trialkylsilyl, aryldialkylsilyl, alkyldiarylsilyl or triaarylsilyl group; (b) reacting the compound of step (a) with a compound having structure: ##STR40## under suitable conditions to form a compound having the structure: ##STR41## wherein R is a trialkylsilyl, aryldialkylsilyl, alkyldiarylsilyl or triaarylsilyl group; (c) reacting the compound formed in step (b) with a compound having the structure: ##STR42## under suitable conditions to form a compound having the structure: ##STR43## wherein R a trialkylsilyl, aryldialkylsilyl, alkyldiarylsilyl or triaarylsilyl group; (d) deprotecting and re-protecting the compound formed in step (c) under suitable conditions to form a compound having the structure: ##STR44## wherein R is TIPS; (e) iodosulfonamidating the compound formed in step (d) under suitable conditions to form a compound having the structure: ##STR45## (f) reacting the compound formed in step (e) with a compound having the structure: ##STR46## under suitable conditions to form a compound having the structure: ##STR47## wherein R is H; (g) deprotecting and peracetylating the compound formed in step (f) under suitable conditions to form a compound having the structure: ##STR48## (h) epoxidizing the compound formed in step (g) under suitable conditions to form an epoxide thereof and reacting the epoxide under suitable conditions to form a compound having the structure: ##STR49## wherein R is a substituted or unsubstituted allyl group; and (i) treating the compound formed in step (h) under suitable conditions to form a compound having the structure: ##STR50## wherein R is a substituted or unsubstituted allyl group. In the above process the suitable conditions necessary for the various reactions and treatments may be found in the Experimental Details section which follows hereinafter. However, it is within the confines of the present invention that the specific reagents and solvents provided as well as the specific conditions necessary for reaction or treatment may be substituted with other suitable reactants, solvents and conditions well known to those skilled in the art. The allyl compound may be conjugated to a peptide or protein via amine or carboxylic acid side chain. In practicing the invention, a bioconjugate is prepared according to the protocol of Bernstein and Hall (Carbohydr. Res. 1980, 78, C1). The allyl group is ozonolyzed to form either an aldehyde or carboxylic acid, which is condensed to a terminal amine to form, respectively, an imine or an amide. The imine is reduced with sodium borohydride to the amine. Alternatively, the aldehyde is reductively aminated using procedures known in the art to form an amine which is reacted with a side-chain terminal carboxylic acid to form an amide conjugate. The invention provides a pharmaceutical composition which comprises a therapeutically effective amount of the compound disclosed hereinabove and a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers are well known to those skilled in the art and include, but are not limited to, 0.01-0.1M and preferably 0.05M phosphate buffer or 0.8% saline. Additionally, such pharmaceutically acceptable carriers may be aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's or fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers such as those based on Ringer's dextrose, and the like. Preservatives and other additives may also be present, such as, for example, antimicrobials, antioxidants, chelating agents, inert gases and the like. The invention further provides a method for treating a subject afflicted with a disorder caused by Helicobacter pylori which comprises administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed hereinabove so as to treat the subject afflicted with the disorder. In one embodiment, the invention provides a method of treating a subject afflicted with gastric or duodenal ulcer. In another embodiment, the invention provides a method of treating a subject afflicted with gastric adenocarcinoma. In addition, the invention provides a method for inhibiting the adhesion of Helicobacter pylori to gastric epithelium in a subject which comprises administering to the subject an amount of the compound disclosed hereinabove effective to inhibit the adhesion of Helicobacter pylori to gastric epithelium in the subject. The present invention also provides a process for synthesizing a compound having the structure: ##STR51## wherein R is H which comprises: (a)(i) reacting a compound having the structure: ##STR52## with an epoxidizing agent under suitable conditions to form an epoxide; (ii) cleaving the epoxide formed in step (a)(i) under suitable conditions with R.sub.4 NF wherein each R is independently the same or different and is a linear or branched chain alkyl, aralkyl or aryl group to form a fluoroalcohol; and (iii) alkylating the fluoroalcohol formed in step (b)(ii) under suitable conditions with a non-nucleophilic base and an organic halide having the formula C.sub.6 H.sub.5 CH.sub.2 X wherein X is Br, Cl, I or F to form a compound having the structure: ##STR53## (b)(i) synthesizing a compound having the structure: ##STR54## (c)(i) treating the compound formed in step (b) with an epoxidizing agent under suitable conditions to form an epoxide; and (ii) coupling the epoxide formed in step (c)(i) with a compound having the structure: ##STR55## under suitable conditions to form a compound having the structure: ##STR56## (d)(i) alkylating the compound formed in step (c)(ii) under suitable conditions with a non-nucleophilic base and an organic halide having the formula C.sub.6 H.sub.5 CH.sub.2 X wherein X is Br, Cl, I or F; and (ii) de-silylating the compound formed in step (d)(i) under suitable conditions with R.sub.4 NF wherein each R is independently the same or different and is a linear or branched chain alkyl, aralkyl or aryl group; (iii) treating the compound formed in step (d)(ii) under suitable conditions with a metal alkoxide to form a deprotected disaccharide; and (iv) alkylating the disaccharide formed in step (d)(iii) under suitable conditions to form a selectively deprotected disaccharide having the structure: ##STR57## (e)(i) coupling the selectively deprotected disaccharide formed in step (d)(iv) with the compound formed in step (a)(iii) under suitable conditions to form a protected trisaccharide; and (ii) de-protecting the protected trisaccharide formed in step (e)(i) under suitable conditions to form a trisaccharide having the structure: ##STR58## wherein R is H. In step (a) reaction (i) may be carried out using a variety of epoxidizing agents including peracetic acid, m-chlorobenzoic acid, trifluoroacetic acid, and hydrogen peroxide. A preferred agent is 3,3-dimethyldioxirane. Non-nucleophilic, inert solvents may be used, such as dichloromethane. Reaction (a)(ii) may be performed using organic ammonium fluoride salts, including tetrabutylammonium fluoride, in a range of solvents, including ethereal solvents, preferably in tetrahydrofuran. Step (iii) may be performed using a non-nucleophilic base such as sodium hydride in a non-nucleophilic solvent such as DMF. In step (b) the compound shown may be prepared as described herein. Step (c)(i) may be carried out using a variety of epoxidizing agents including peracetic acid, m-chlorobenzoic acid, trifluoroacetic acid, and hydrogen peroxide, 3,3-dimethyldioxirane being preferred, in non-nucleophilic, inert solvents, such as dichloromethane. Coupling step (c)(ii) may be carried out using a metal catalyst, such as zinc chloride, in an inert solvent, such as THF. Step (d)(i) is carried out using a non-nucleophilic base such as sodium hydride in a non-nucleophilic solvent such as DMF. In step (d)(ii) de-silylation is effected using an organic ammonium fluoride salt, including tetrabutylammonium fluoride, in a range of solvents, including ethereal solvents, preferably in tetrahydrofuran. The carbonate ester is cleaved using a metal alkoxide, such as sodium methoxide, in an alcoholic medium such as methanol. Step (d)(iv) is selectively performed using a metal oxide, such as (n--Bu.sub.3 Sn).sub.2 O, in the presence of an organic ammonium bromide, such as tetra-n-butylammonium bromide, in an inert solvent such as benzene. Step (e) is a coupling performed in the presence of a metal halide salt, such as SnCl.sub.2, in the presence of silver perchlorate and 2,6-di-t-butylpyridine, in a solvent, such as ether, containing molecular sieves. Oxidative removal of PMB is performed with an oxidizing agent such as DDQ in an inert solvent system, which may preferably be heterogeneous, for example, using water/dichloromethane. The present invention also provides a process for synthesizing a trisaccharide ceramide having the structure: ##STR59## which comprises: (a) synthesizing a trisaccharide having the structure: ##STR60## wherein R is PMB; (b)(i) reacting the trisaccharide formed in step (a) with an epoxidizing agent under suitable conditions to form a trisaccharide epoxide; and (ii) reacting the trisaccharide epoxide formed in step (b)(i) with a compound having the structure: ##STR61## under suitable conditions to form a protected trisaccharide ceramide having the structure: ##STR62## (c)(i) acylating the ceramide formed in step (b)(ii) under suitable conditions; and (ii) selectively de-protecting the compound formed in step (c)(i) under suitable conditions to form the trisaccharide ceramide. In step (a) the trisaccharide may be synthesized as described herein. Step (b)(i) is performed using using a variety of epoxidizing agents including peracetic acid, m-chlorobenzoic acid, trifluoroacetic acid, and hydrogen peroxide, 3,3-dimethyldioxirane being preferred, in non-nucleophilic, inert solvents, such as dichloromethane. Coupling step (b)(ii) may be carried out using a tributyltin ether of the ceramide precursor and a metal catalyst, such as zinc chloride, in an inert solvent, such as THF. In step (c)(i) acylation is performed using a linear or branched chain alkyl anhydride preferably acetic anhydride or halide in the presence of triethylamine and DMAP in an inert organic solvent such as dichloromethane. The PMB protecting group is removed oxidatively, preferably as described above. The present invention further provides a process for synthesizing a mercaptotrisaccharide having the structure: ##STR63## which comprises: (a)(i) synthesizing a compound having the structure: ##STR64## (ii) coupling the compound of step (a)(i) with a compound having structure: ##STR65## under suitable conditions to form a disaccharide having the structure: ##STR66## (b) coupling the disaccharide formed in step (a)(ii) with a compound having the structure: ##STR67## under suitable conditions to form a trisaccharide having the structure: ##STR68## (c) iodosulfonamidating the trisaccharide formed in step (b) under suitable conditions to form a iodosulfonamide having the structure: ##STR69## and (d) reacting the iodosulfonamide formed in step (c) under suitable conditions with a thiolate to form the mercaptotrisaccharide. Step (a)(ii) is performed by reacting the compound of step (a)(i), which may be obtained as described herein or otherwise, with a variety of epoxidizing agents including peracetic acid, m-chlorobenzoic acid, trifluoroacetic acid, and hydrogen peroxide, 3,3-dimethyldioxirane being preferred, in non-nucleophilic, inert solvents, such as dichloromethane, followed by coupling with the diol monosaccharide of step (a)(ii) which may be carried out using a metal catalyst, such as zinc chloride, in an inert solvent, such as THF. Coupling with the fluorosugar is carried out in step (b) in the presence of a metal halide salt, such as SnCl.sub.2, in the presence of silver perchlorate and 2,6-di-t-butylpyridine, in a solvent, such as ether, containing molecular sieves. Step (c) is performed using I(coll).sub.2 perchlorate and PhSO.sub.2 NH.sub.2 in the presence of molecular sieves. Step (d) is carried out using alkyl thiol and a base such as LiHMDS in an inert solvent as DMF. The present invention also provides a process of synthesizing a hexasaccharide ceramide having the structure: ##STR70## which comprises: (a) coupling a compound having the structure: ##STR71## with a compound having the structure: ##STR72## under suitable conditions to form a compound having the structure: ##STR73## (b)(i) reacting the compound formed in step (a) with an epoxidizing agent under suitable conditions to form a hexasaccharide epoxide; and (ii) reacting the hexasaccharide epoxide with a stannyl ether having the structure: ##STR74## under suitable conditions to form a hexasaccharide alcohol; (c) acylating the hexasaccharide alcohol formed in step (b)(ii) under suitable conditions to form a hexasaccharide acetate having the structure: ##STR75## (d) reductively acylating the hexasaccharide acetate formed in step (c) under suitable conditions in the presence of palmitic anhydride to form a hexasaccharide ceramide; (e) desilylating and partially deprotecting the hexasacchararide ceramide under suitable conditions to form a partially deprotected hexasaccharide ceramide; (f)(i) reducing the partially deprotected hexasaccharide ceramide under suitable conditions to form a deprotected hexasaccharide ceramide acetate; and (ii) acylating the deprotected hexasaccharide ceramide acetate under suitable conditions to form a hexasaccharide ceramide peracetate; and (g) saponifying the hexasaccharide ceramide peracetate under suitable conditions to form the hexasaccharide ceramide. Step (a) is performed using triflate esters, such as methyl triflate, in the presence of molecular sieves in an inert solvent. Step (b)(i) is carried out using a variety of epoxidizing agents including peracetic acid, m-chlorobenzoic acid, trifluoroacetic acid, and hydrogen peroxide, 3,3-dimethyldioxirane being preferred, in non-nucleophilic, inert solvents, such as dichloromethane. Step (b)(ii) is performed using a stannyl ether of the ceramide precursor, preferably the tri-n-butyl stannylether, in the presence of a metal salt, such as Zn triflate, in an inert solvent, such as THF. Step (c) is carried out using acetic anhydride in the presence of a base such as triethylamine and DMAP. Step (d) is carried out using a noble metal catalyst such as Lindlar's catalyst and hydrogen gas in the presence of palmitic anhydride in an inert solvent such as ethyl acetate. Desilylation step (e) is effected using organic ammonium fluoride salts, such as tetra-n-butylammonium fluoride in THF. The carbonate ester is cleaved using a metal alkoxide such as NaOMe in an alcohol such as methanol. In step (f)(i) reduction is performed using a metal such as lithium or sodium in liquid ammonia and an inert solvent such as THF. Step (f)(ii) is carried out using acetic anhydride in the presence of a base such as Et.sub.3 N and DMAP in an inert solvent such as dichloromethane. The peracetate is saponified using a metal alkoxide such as sodium methoxide in an alcohol such as methanol. The present invention also provides a process of synthesizing a hexasaccharide ceramide having the structure: ##STR76## which comprises: (a) coupling a compound having the structure: ##STR77## with a compound having the structure: ##STR78## under suitable conditions to form a hexasaccharide having the structure: ##STR79## and (b)(i) reducing the hexasaccharide formed in step (a) under suitable conditions in the presence of palimitic anhydride to form a palmitoyl amide; (ii) desilylating the palmitoyl amide with R.sub.4 NF wherein each R is independently the same or different and is a linear or branched chain alkyl, aralkyl or aryl group under suitable conditions to form a partially deprotected hexasaccharide; (iii) de-protecting the hexasaccharide formed in step (b)(ii) under suitable conditions to form a deprotected hexasaccharide; (iv) acylating the hexasaccharide formed in step (b)(iii) under suitable conditions to form a hexasaccharide ceramide peracetate; and (v) saponifying the hexasaccharide ceramide peracetate under suitable conditions to form the hexasaccharide ceramide. Step (a) is performed using triflate esters, such as methyl triflate, in the presence of molecular sieves in an inert solvent. Step (b)(i) is carried out using using a noble metal catalyst such as Lindlar's catalyst and hydrogen gas in the presence of palmitic anhydride in an inert solvent such as ethyl acetate. Step (b)(ii) is performed using organic ammonium fluoride salts, such as tetra-n-butylammonium fluoride in THF. In step (b)(iii) reduction is performed using a metal such as lithium or sodium in liquid ammonia and an inert solvent such as THF. Step (b)(iv) is carried out using acetic anhydride in the presence of a base such as Et.sub.3 N and DMAP in an inert solvent such as dichloromethane. In step (v) the peracetate carbonate is saponified using a metal alkoxide such as sodium methoxide in an alcohol such as methanol. The present invention also provides a process of synthesizing an allyl hexasaccharide having the structure: ##STR80## which comprises: (a) coupling a compound having the structure: ##STR81## with a compound having the structure: ##STR82## wherein R is H under suitable conditions to form a hexasaccharide having the structure: ##STR83## (b)(i) desilylating the compound formed in step (a) with R.sub.4 NF wherein each R is independently the same or different and is a linear or branched chain alkyl, aralkyl or aryl group under suitable conditions to form a partially deprotected hexasaccharide; (ii) de-protecting the hexasaccharide formed in step (b)(i) under suitable conditions to form a deprotected hexasaccharide; and (iii) peracylating the compound formed in step (b)(ii) under suitable conditions to form a hexasaccharide peracetate having the structure: ##STR84## (c)(i) reacting the hexasaccharide peracetate formed in step (b)(iii) with an epoxidizing agent under suitable conditions to form an hexasaccharide epoxide peracetate; (ii) treating the hexasaccharide epoxide peracetate formed in step (c)(i) with allyl alcohol under suitable conditions to form an allyl hexasaccharide peracetate; and (iii) saponifying the allyl hexasaccharide peracetate under suitable conditions to form the allyl hexasaccharide. Step (a) is performed using triflate esters, such as methyl triflate, in the presence of molecular sieves in an inert solvent. Step (b)(i) is carried out using organic ammonium fluoride salts, such as tetra-n-butylammonium fluoride in THF. Step (b)(ii) is performed using a metal alkoxide such as sodium methoxide in an alcohol such as methanol, followed by reduction performed using a metal such as lithium or preferably sodium in liquid ammonia and an inert solvent such as THF. Step (b)(iii) is carried out using acetic anhydride in the presence of a base such as Et.sub.3 N and DMAP in an inert solvent such as dichloromethane. In step (c)(i) is carried out using a variety of epoxidizing agents including peracetic acid, m-chlorobenzoic acid, trifluoroacetic acid, and hydrogen peroxide, 3,3-dimethyldioxirane being preferred, in non-nucleophilic, inert solvents, such as dichloromethane. Step (c)(ii) is carried out using allyl alcohol in an inert solvent. Step (c)(iii) the peracetate carbonate is saponified using a metal alkoxide such as sodium methoxide in an alcohol such as methanol. The present invention provides a process of synthesizing a hexasaccharide having the structure: ##STR85## which comprises: (a) coupling a compound having the structure: ##STR86## with a compound having the structure: ##STR87## under suitable conditions to form a compound having the structure: ##STR88## (b)(i) acylating the compound formed in step (a) under suitable conditions; and (ii) reacting the compound formed in step (b)(i) with an epoxidizing agent under suitable conditions to form an epoxide having the structure: ##STR89## (c)(i) treating the epoxide with R.sub.4 NF wherein each R is independently the same or different and is a linear or branched chain alkyl, aralkyl or aryl group under suitable conditions; and (ii) alkylating the compound formed in step (c)(i) under suitable conditions to form a compound having the structure: ##STR90## wherein R is H or acyl; (d) coupling the compound formed in step (c)(ii) with a compound having the structure: ##STR91## under suitable conditions to form the hexasaccharide. Step (a) is performed using a metal catalyst such as silver tetrafluoroborate in an inert solvent. Step (b)(i) is carried out using acetic anhydride in the presence of a base such as Et.sub.3 N and DMAP in an inert solvent such as dichloromethane. Step (b)(ii) is carried out using a variety of epoxidizing agents including peracetic acid, m-chlorobenzoic acid, trifluoroacetic acid, and hydrogen peroxide, 3,3-dimethyldioxirane being preferred, in non-nucleophilic, inert solvents, such as dichloromethane. Step (c)(i) is effected with organic ammonium fluoride salts, such as tetra-n-butylammonium fluoride in THF. Step (c)(ii) is performed using a non-nucleophilic base such as sodium hydride in an inert solve. Step (d) is performed using a metal salt catalyst such as tin dichloride in the presence of silver perchlorate in an inert solvent such as di-t-butylpyridine. Further transformations provide deprotected products or conjugates with proteins or other carriers. The present invention further provides a compound having the structure: ##STR92## wherein n is an integer between about 0 and about 9. The allyl glycoside shown is prepared using the glycal coupling methods taught herein, and may be bound to protein carriers using general reactions described herein or by standard methods in the art. For example, the allyl glycoside may be prepared by coupling compound 9b disclosed herein with a suitably protected 8b, followed by coupling with 12b, then coupling with allyl alcohol and an appropriate deprotection sequence. The present invention also provides a compound having the structure: ##STR93## wherein n is an integer between about 0 and about 9. The allyl glycoside shown is prepared using the glycal coupling methods, allylation and a deprotection sequence as taught herein (see FIG. 12), and may be bound to protein carriers using general reactions described herein or by standard methods in the art. The present invention also provides a compound having the structure: ##STR94## wherein n is an integer between about 0 and about 9. The allyl glycosides shown are prepared using the glycal coupling methods taught herein, and may be bound to protein carriers using general reactions described herein or by standard methods in the art. It is within the scope of the present invention to vary the combination of protecting groups for the various sugar hydroxyl groups in accord with ordinary skill in the art. The present invention provides a method of inducing antibodies in a human subject, wherein the antibodies are immunoreactive with human breast tumor cells, which comprises administering to the subject an amount of a compound having the structure: ##STR95## alone or bound to a suitable immunological adjuvant effective to induce the antibodies. In one embodiment, the present invention provides a method wherein the antibodies induced are MBr1 antibodies. In another embodiment, the present invention provides a method wherein the subject is in clinical remission or, where the subject has been treated by surgery, has limited unresected disease. In another embodiment, the present invention provides a method wherein the adjuvant is a protein carrier, bacteria or liposomes. In yet another embodiment, the present invention provides wherein the adjuvant is bacille Calmette-Guerin (BCG). The present invention provides a method of preventing recurrence of breast cancer in a subject which comprises vaccinating the subject with the compound shown hereinabove either alone or bound to a suitable immunological carrier, adjuvant or vehicle. The present invention also provides a method of inducing antibodies in a subject, wherein the antibodies are immunoreactive with human breast tumor cells, which comprises administering to the subject an amount of the compound having the structure: ##STR96## wherein n is an integer between about 0 and about 9 either alone or bound to a suitable immunological adjuvant effective to induce the antibodies. In one embodiment, the present invention provides a method wherein the antibodies induced are MBr1 antibodies. In another embodiment, the present invention provides a method wherein the subject is in clinical remission or, where the subject has been treated by surgery, has limited unresected disease. In another embodiment, the present invention provides a method wherein the adjuvant is a protein carrier, bacteria or liposomes. In yet another embodiment, the present invention provides wherein the adjuvant is bacille Calmette-Guerin. The present invention provides a method of preventing recurrence of breast cancer in a subject which comprises vaccinating the subject with the compound shown hereinabove either alone or bound to a suitable immunological carrier, adjuvant or vehicle. The present invention also provides a method of inducing antibodies in a subject, wherein the antibodies are immunoreactive with human breast tumor cells, which comprises administering to the subject an amount of the compound having the structure: ##STR97## wherein n is an integer between about 0 and about 9 either alone or bound to a suitable immunological adjuvant effective to induce the antibodies. In one embodiment, the present invention provides a method wherein the antibodies induced are MBr1 antibodies. In another embodiment, the present invention provides a method wherein the subject is in clinical remission or, where the subject has been treated by surgery, has limited unresected disease. In another embodiment, the present invention provides a method wherein the adjuvant is a protein carrier, bacteria or liposomes. In yet another embodiment, the present invention provides wherein the adjuvant is bacille Calmette-Guerin. The present invention also provides a method of preventing recurrence of breast cancer in a subject which comprises vaccinating the subject with the compound shown hereinabove either alone or bound to a suitable immunological carrier, adjuvant or vehicle. The present invention additionally provides a method of inducing antibodies in a subject, wherein the antibodies are immunoreactive with human breast tumor cells, which comprises administering to the subject an amount of the compound having the structure: ##STR98## wherein n is an integer between about 0 and about 9 either alone or bound to a suitable immunological adjuvant effective to induce the antibodies. In one embodiment, the present invention provides a method wherein the antibodies induced are MBr1 antibodies. In another embodiment, the present invention provides a method wherein the subject is in clinical remission or, where the subject has been treated by surgery, has limited unresected disease. In another embodiment, the present invention provides a method wherein the adjuvant is a protein carrier, bacteria or liposomes. In yet another embodiment, the present invention provides wherein the adjuvant is bacille Calmette-Guerin. The present invention also provides a method of preventing recurrence of breast cancer in a subject which comprises vaccinating the subject with the compound shown hereinabove either alone or bound to a suitable immunological carrier, adjuvant or vehicle. Experimental Details General Procedures All air- and moisture-sensitive reactions were performed in a flame-dried apparatus under an argon atmosphere unless otherwise noted. Air-sensitive liquids and solutions were transferred via syringe or canula. Wherever possible, reactions were monitored by thin-layer chromatography (TLC). Gross solvent removal was performed in vacuum under aspirator vacuum on a Buchi rotary evaporator, and trace solvent was removed on a high vacuum pump at 0.1-0.5 mmHg. Melting points (mp) were uncorrected and performed in soft glass capillary tubes using an Electrothermal series IA9100 digital melting point apparatus. Infrared spectra (IR) were recorded using a Perkin-Elmer 1600 series Fourier-Transform instrument. Samples were prepared as neat films on NaCl plates unless otherwise noted. Absorption bands are reported in wavenumbers (cm.sup.-1). Only relevant, assignable bands are reported. Proton nuclear magnetic resonance (.sup.1 H NMR) spectra were determined using a Bruker AMX-400 spectrometer at 400 MHz. Chemical shifts are reported in parts per million (ppm) downfield from tetramethylsilane (TMS; .delta.=0 ppm) using residual CHCl.sub.3 as a lock reference (.delta.=7.25 ppm). Multiplicities are abbreviated in the usual fashion: s=singlet; d=doublet; t=triplet; q=quartet; m=multiplet; br=broad. Carbon nuclear magnetic resonance (.sup.13 C NMR) spectra were performed on a Bruker AMX-400 spectrometer at 100 MHz with composite pulse decoupling. Samples were prepared as with .sup.1 H NMR spectra, and chemical shifts are reported relative to TMS (0 ppm); residual CHCl.sub.3 was used as an internal reference (.delta.=77.0 ppm). All high resolution mass spectral (HRMS) analyses were determined by electron impact ionization (EI) on a JEOL JMS-DX 303HF mass spectrometer with perfluorokerosene (PFK) as an internal standard. Low resolution mass spectra (MS) were determined by either electron impact ionization (EI) or chemical ionization (CI) using the indicated carrier gas (ammonia or methane) on a Delsi-Nermag R-10-10 mass spectrometer. For gas chromatography/mass spectra (GCMS), a DB-5 fused capillary column (30 m, 0.25 mm thickness) was used with helium as the carrier gas. Typical conditions used a temperature program from 60-250.degree. C. at 40.degree. C./min. Thin layer chromatography (TLC) was performed using precoated glass plates (silica gel 60, 0.25 mm thickness). Visualization was done by illumination with a 254 nm UV lamp, or by immersion in anisaldehyde stain (9.2 mL p-anisaldehyde in 3.5 mL acetic acid, 12.5 mL conc. sulfuric acid and 338 mL 95% ethanol (EtOH)) and heating to colorization. Flash silica gel chromatography was carried out according to the standard protocol. Unless otherwise noted, all solvents and reagents were commercial grade and were used as received, except as indicated hereinbelow, where solvents were distilled under argon using the drying methods listed in paretheses: CH.sub.2 Cl.sub.2 (CaH.sub.2); benzene (CaH.sub.2); THF (Na/ketyl); Et.sub.2 O (Na/ketyl); diisopropylamine (CaH.sub.2).
Abbreviations
OTf triflate
TLC thin layer chromatography
EtOAc ethyl acetate
TIPS triisopropylsilyl
PMB p-methoxybenzyl
Bn benzyl
Ac acetate
hex hexane
THF tetrahydrofuran
coll collidine
LiHMDS lithium hexamethyldisilazide
DAST diethylaminosulfur trifluoride
DMF N,N-dimethylformamide
DMAP 2-dimethylaminopyridine
DDQ 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
TBAF tetra-n-butylammonium fluoride
M.S. molecular sieves
r.t. room temperature
r.b. round bottom flask
EXAMPLE 1 Preparation of Polymer-bound Glucal 18 Polymer-bound galactal 7 (500 mg; S. J. Danishefsky, et al., J. Am. Chem. Soc. 1992, 8331) was placed in a 100 mL polymer flask and dried in vacuo. On cooling to 0.degree. C. under N.sub.2, dry CH.sub.2 Cl.sub.2 (20 mL) and freshly prepared Murray solution (30 mL; R. W. Murray and R. Jeyaraman, J. Org Chem. 1985, 2847) was added. After stirring at 0.degree. C. for .about.90 min., solubles were filtered using N.sub.2 pressure. The oxidation procedure was repeated. The resulting epoxide of 7 kept on a vacuum line for .about.3 h to dry. A solution of glucal 19 (1.0 g in 8 mL dry THF) was added, and the mixture was cooled to -23.degree. C. (dry ice-CCl.sub.4). A solution of ZnCl.sub.2 in THF (0.8 mL 1.0 M) was added. The mixture was slowly allowed to warm to r.t. (over .about.2 h), and then stirred at r.t. overnight. The polymer-bound glucal 18 was rinsed with 3.times.20 mL THF, and dried on a vacuum line. Preparation of Polymer-bound Tetrasaccharide 20 Polymer-bound glucal 18 and Sn(OTf).sub.2 (0.80 g, 1.92 mmol) were combined and dried in vacuo. On cooling to 0.degree. C. under N.sub.2, a solution of fucosyl donor 10 (1.8 g, 4.1 mmol) in 20 mL dry THF with di-t-butylpyridine (1.7 mL, 7.57 mmol) was added. The mixture was allowed to warm slowly to r.t., and stirred overnight. The polymer was washed with 2.times.20 mL dry THF, 2.times.20 mL dry dioxane, 20 mL DMSO, and 2.times.20 mL THF. The resulting polymer-bound tetrasaccharide 20 was kept on a vacuum line to dry. Preparation of Tetrasaccharide Glycal 21 The polymer-bound tetrasaccharide 20 (50 mg) was stirred in 2 mL THF, and treated with 0.2 mL each of 1.0 M solutions of TBAF and AcOH in THF. The mixture was stirred at 40.degree. C. overnight. The polymer was washed with 3.times.5 mL THF. The combined rinsings were concentrated and column-chromatographed on silica (2:1 EtOAc:hex), providing tetrasaccharide glycal 21 as a colorless gum. Yield: 9.0 mg. EXAMPLE 2 Preparation of Diol 18' Galactal 7' (0.100 g, 0.304 mmol) in 5 mL dry CH.sub.2 Cl.sub.2 at 0.degree. C. under a N.sub.2 atmosphere was treated with 10 mL Murray solution (freshly prepared) and stirred at 0.degree. C. for 40 min. TLC (1:1 EtOAc:hex) showed no trace of 7'. Solvents were evaporated using a dry N.sub.2 stream. The residual epoxide of 7' was kept on a vac. line .about.2 h. To the epoxide under a N.sub.2 atmosphere was added a solution of glucal derivative 3' (0.150 g, 0.496 mmol) in 3 mL dry THF. On cooling to -78.degree. C., 1.0 M ZnCl.sub.2 in Et.sub.2 O (0.50 mL, 0.50 mmol) was added. The mixture was allowed to slowly warm to r.t. (over .about.2 h) and stirred overnight. TLC (1:1 EtOAc:hex) showed that the reaction was complete. Saturated aq. NaHCO.sub.3 (20 mL) was added, and the mixture was then extracted with EtOAc (3.times.20 mL). The organic layer was dried over MgSO.sub.4. Column chromatography on silica (1:3 EtOAc:hex) afforded diol 18' as a colorless solid. Yield: 173 mg (89%). [.alpha.].sub.D.sup.23 -9.8.degree. (c 1.0, CH.sub.2 Cl.sub.2). Preparation of Tetrasaccharide 22 Diol 18' (86 mg, 0.133 mmol) and fucosyl donor 10 (0.290 g, 0.665 mmol) were azeotropically dried using benzene. The mixture was dissolved in 3 mL dry THF together with 0.65 mL di-t-butylpyridine and then added via canula to a flask containing Sn(OTf).sub.2 (0.30 g, 0.72 mmol) and 4 .ANG. MS (500 mg) at 0.degree. C. under N.sub.2 atm. The mixture was stirred at 0.degree. C. .about.7 h. TLC (1:3 EtOAc:hex) shows no trace of diol 18'. The mixture was partitioned between saturated aq. NaHCO.sub.3 (100 mL) and EtOAc (2.times.100 mL). The organic layer was dried over MgSO.sub.4. The organic layer was filtered through silica using EtOAc to obtain crude material, which was then purified by chromatography on silica (1:9 EtOAc:hex) affording tetrasaccharide 22. Yield: 170 mg (86%). Preparation of Iodosulfonamide 23 Procedure 1 Tetrasaccharide glycal 22 (120 mg, 81.1 mmol) and PhSO.sub.2 NH.sub.2 (20 mg, 0.13 mmol) were azeotropically dried using benzene. Added (glove bag) 4 .ANG. MS (0.2 g). After cooling to 0.degree. C. under N.sub.2, dry CH.sub.2 Cl.sub.2 (1.0 mL) was added. The mixture was treated with a solution of I(coll).sub.2 ClO.sub.4 (prepared from 100 mg Ag(coll).sub.2 ClO.sub.4, 5 mL collidine, and 60 mg I.sub.2 in 1 mL dry CH.sub.2 Cl.sub.2) via canula through a plug of flame-dried celite and 4 .ANG. MS. The mixture was stirred at 0.degree. C. for 40 min. TLC (1:4 EtOAc:hex) showed iodosulfonamide 23 as the major component. The mixture was filtered through celite, which was rinsed with Et.sub.2 O. The organic layer was extracted with saturated aq. Na.sub.2 S.sub.2 O.sub.3 saturated aq. CUSO.sub.4, brine, and then dried over MgSO.sub.4. Column chromatography on silica (1:4 EtOAc:hex) gave iodosulfonamide 23 as a colorless solid. Yield: 115 mg (80%). Procedure 2 Tetrasaccharide glycal 22 (200 mg, 0.135 mmol), PhSO.sub.2 NH.sub.2 (42 mg, 0.27 mmol), and 200 mg powdered 4 .ANG. MS in 2.0 mL dry CH.sub.2 Cl.sub.2 at 0.degree. C. under a N.sub.2 atmosphere was treated with I(coll).sub.2 ClO.sub.4 (prepared from 120 mg Ag(coll).sub.2 ClO.sub.4 and 67 mg I.sub.2 in 1 mL dry CH.sub.2 Cl.sub.2). The mixture was stirred at 0.degree. C. (protected from light using foil) for 30 min. TLC (1:2 EtOAc:hex) showed mainly iodosulfonamide with some glycal. After .about.1 h more at 0.degree. C., TLC showed no noticeable improvement. The mixture was filtered through celite, which was washed with Et.sub.2 O. After extracting with saturated aq. Na.sub.2 S.sub.2 O.sub.3, saturated aq. CuSO.sub.4, brine, the organics were dried over MgSO.sub.4. Column chromatography on silica (1:3 EtOAc:hex) gave 23 as a colorless solid. Yield: 165 mg (69%). [.alpha.].sub.D.sup.23 =-85.7.degree. (c 1.0, CH.sub.2 Cl.sub.2). Preparation of Hexasaccharide 25 Iodosulfonamide 23 (60 mg, 34 mmol) in a 35 mL r.b. was treated with 200 mg powdered 4 .ANG. MS (glove bag). To this flask under N.sub.2 was added a solution of protected lactal 24 in THF (1.5 mL). On cooling the mixture to -78.degree. C., a solution of AgBF.sub.4 (40 mg, 0.206 mmol) was added in 0.25 mL dry THF. The mixture was stirred and slowly warmed to r.t. overnight. The mixture was warmed to 45.degree. C. and stirred .about.36 h. TLC showed only a trace of iodosulfonamide. Saturated aq. NH.sub.4 Cl (5 mL) was added, and the mixture was extracted with 3.times.10 mL EtOAc. The organic layer was dried over MgSO.sub.4. Column chromatography on silica (1:3 EtOAc:hex) afforded 25 as a colorless oil. Yield: 42 mg (55%). [.alpha.].sub.D.sup.23 =-33.8.degree. (c 2.0, CH.sub.2 Cl.sub.2) Preparation of Hexasaccharide 25a Hexasaccharide 25 (55 mg, 24.4 mmol) in .about.1.5 mL THF was treated at 0.degree. C. with TBAF (0.25 mL, 1.0 M solution in THF, 0.25 mmol), and stirred at r.t. overnight. TLC (1:9 MeOH:CH.sub.2 Cl.sub.2) showed a 3:1 mixture of 25a vs. a less polar substance. Additional 1.0 M TBAF (0.10 mL) was added, and the mixture was stirred overnight at r.t. TLC showed that the reaction was complete. Solvents were removed using a N.sub.2 stream. Column chromatography on silica (1:19 MeOH: CH.sub.2 Cl.sub.2) afforded a .about.1:2 mixture corresponding to two compounds which differ only in the presence or absence of a 3,4-cyclic carbonate group. Crude yield: 35 mg total weight for two products. The crude mixture was used as such for the next reaction. Preparation of Peracetylated Hexasaccharide 26 Hexasaccharide 25a (36 mg) in 0.25 mL dry THF was added via canula to .about.8 mL bright blue Na/NH.sub.3 solution at -78.degree. C. (dry ice bath) under N.sub.2 atm. After removing the dry ice bath, the mixture was stirred in refluxing NH.sub.3 (dry ice condenser) for 15 min. After adding 2 mL dry MeOH (slowly!), the resulting mixture was stirred while blowing off NH.sub.3 with a N.sub.2 stream. The MeOH solution was treated with Dowex 50.times.8 [H.sup.+ ] until pH .about.8-9, and then filtered. The resin was washed with MeOH. The residue was concentrated and kept on a vacuum line to dry. Under a N.sub.2 atmosphere, the residue was treated with 1 mL dry pyridine and 0.5 mL Ac.sub.2 O, and stirred at r.t. overnight. TLC (EtOAc) showed that hexasaccharide 26 is major component. Upon concentration, the residue was purified by column chromatography on silica (1:4 hex:EtOAc). Preparation of Hexasaccharide 17 Hexasaccharide 26 (10.0 mg, 6.3 mmol) under N.sub.2 at 0.degree. C. was treated with 0.5 mL dry CH.sub.2 Cl.sub.2. Dioxirane solution (0.20 mL) was added, and the mixture was stirred at 0.degree. C. .about.40 min. TLC (EtOAc) showed no trace of 26. Solvents were evaporated with a N.sub.2 stream. The epoxide was dried on a vacuum line for .about.2 h. The epoxide was treated under a N.sub.2 atmosphere with 0.5 mL allyl alcohol (passed through basic alumina to dry) and 0.5 mL dry THF. On cooling to -78.degree. C., 1.0 M ZnCl.sub.2 (10 mL) in dry Et.sub.2 O was added. After warming slowly to r.t., the mixture was stirred overnight. Saturated aq. NaHCO.sub.3 (5 mL) was added, and the mixture was extracted with 3.times.5 mL EtOAc. The combined organic layers were dried over MgSO.sub.4, filtered and concentrated to an oil, which was dried on a vacuum line for .about.2 h. The residue was treated to pyridine:Ac.sub.2 O (2:1, 1.5 mL) while stirring overnight. Solvents were removed, and the residue was purifed by column chromatography on silica (1:4 hex:EtOAc), affording hexasaccharide 17 as a colorless solid. Yield: 5.5 mg. Results and Discussion A Highly Convergent Synthesis of the Lewis Y Blood Group Determinant in Conjugatable Form Construction of the Le.sup.y determinant commences with lactal (1a)(W. N. Haworth, E. L. Hirst, M. M. T. Plant, R. J. W. Reynolds, J. Chem. Soc. 1930, 2644) as shown in FIG. 2. Capping both primary hydroxyl groups as their TBDPS ethers under standard conditions was followed by simple engagement of the 3' and 4' hydroxyl functions as a cyclic carbonate 2a. The stereospecific introduction of two .alpha.-linked fucose residues gave tetrasaccharide glycal 3a in 51% yield in a single step. The donor used was the known fluorosugar 5a (S. J. Danishefsky, J. Gervay, J. M. Peterson, F. E. McDonald, K. Koseki, T. Oriyama, D. A. Griffith, C-H. Wong, D. P. Dumas, J. Am. Chem. Soc. 1992, 114, 8329) following a modification of the original Mukaiyama conditions. (T. Mukaiyama, Y. Murai, S. Shoda, Chem. Lett. 1981, 431) Glycal 3a corresponds to the Le.sup.y hapten, lacking the N-acetyl function in the glucose residue. The problem was then to introduce this group as well as a galactose spacer module. Methodology developed previously (D. A. Griffith, S. J. Danishefsky, "On the Sulfonamidoglycosylation of Glycals. A Route to Oligosaccharides With 2-Aminohexose Subunits+", J. Am. Chem. Soc. 1990 112, 5811) proved appropriate to attain these goals. Glycal 3a was treated with iodonium dicollidine perchlorate and benzenesulfonamide to afford iodosulfonamide 4a. Azaglycosylation using the 3-stannyl ether of galactal (9a)(S. J. Danishefsky, K. Koseki, D. A. Griffith, J. Gervay, J. M. Peterson, F. E. McDonald, T. Oriyama, J. Am. Chem. Soc. 1992, 114, 8331) in the presence of silver tetrafluoroborate gave pentasaccharide glycal 6a in 75% yield as shown in FIG. 3. Having 6a in hand, one can iterate the azaglycosylation sequence or activate the glycal as its epoxide and continue with further glycosylations. To demonstrate the ability to fashion a conjugatable form of Le.sup.y hapten, formation of the allyl glycoside was important. The feasibility of converting the sulfonamido group into the target acetamide was demonstrated. Glycal 6a was deprotected in two steps as shown. Peracetylation afforded acetamido glycal 7a. Activation of the glycal as its epoxide with dimethyldioxirane (R. L. Halcomb, S. J. Danishefsky, J. Am. Chem. Soc. 1989, 111, 6661), followed by epoxide opening with allyl alcohol in the presence of zinc chloride gave the desired peracetylated .beta.-allyl pentasaccharide which was deacetylated by action of methoxide to provide the target Le.sup.y hapten as its .beta.-allyl glycoside 8a. (8a [.alpha.].sub.D -72.7.degree. (c. 1 MeOH); IR (thin film) 3350, 2940, 2900, 2830, 1650, 1550, 1365, 1300, 1155, 1070, 1030; .sup.1 H NMR (400 MHz, CD.sub.3 OD) .delta.5.95 (m, 1H), 5.32 (d, J=17.25 Hz, 1H), 5.14-5.19 (m, 2H), 5.04 (d, J=3.83 Hz, 1H), 5.02 (d, J=3.50 Hz, 1H). 4.68 (d, J=8.15 Hz, 2H), 4.51 (d, J=5.70 Hz, 1H) 3.40-4.38 (m, 27H). 1.96 (s, 3H), 1.23 (m, 6H); HRMS (FAB) cald for C.sub.35 H.sub.56 NO.sub.24 Na 900.3325 found 900.3310) The aldehyde, derived by ozonolysis of 8a, could be conjugated to a carrier protein by the method of Bernstein and Hall. This synthesis is the most direct route to the Le.sup.y determinant known. (O. Hindsgaul, T. Norberg, J. Le Pendu, R. U. Lemieux, Carbohydr Res. 1982, 109, 109; U. Spohr, R. U. Lemieux ibid. 1988, 174, 211; for previous syntheses, see: J. C. Jacquinet, P. Sinay, J. Org. Chem. 1977, 42, 720; S. Nilsson, H. Lohn, T. Norberg, Glycoconjugate J. 1989, 6, 21; R. R. Schmidt, A. Topfer, Tetrahedron Lett. 1991, 32, 3353; W. Kinzy, A. Low, Carbohydrate. Res. 1993, 245, 193) The method is stereospecific at each step, and it illustrates the versatility of glycals both as donors and acceptors and takes advantage of 1,2-glycal epoxides and their presumed N-sulfonylaziridine counterparts. The method also makes possible extensive analog preparation and variation of conjugation strategies. The synthesis of 3a and 6a are shown below: 3a: To 2.00 g (2.47 mmol) of lactal carbonate 2a was added 4.44 g (9.86 mmol) of fucosyl fluoride 5a. The mixture was azeotroped 5 times with benzene and placed under high vacuum for two hours. Under an argon atmosphere 2.77 ml (12.33 mmol) of di-tert-butyl pyridine and 16 ml of dry ether were added. 2.0 g of freshly activated 4A molecular sieves were added and the mixture stirred one hour at room temperature. In an argon glove bag, 2.34 g (12.33 mmol) of stannous chloride (SnCl.sub.2) and 2.56 g (12.33 mmol) of silver perchlorate (AgClO.sub.4) were added. The flask was equipped with a reflux condenser and the reaction brought to reflux for 72 hours. The reaction was quenched with 5 ml of saturated bicarbonate and filtered through a pad of celite. Diluted with 50 ml ethyl acetate and washed 2 times with sat. bicarbonate, 2 times with sat. copper sulfate and 2 times with sat. brine. The organics were dried over MgSO.sub.4 and concentrated. Flash chromatography in 20% ethyl acetate/hexanes afforded 2.10 g (51%) of a white foam 3a: [.alpha.].sub.D -78.9 (c.555,CHCl.sub.3); IR (thin film) 3040, 3000, 2905, 2860, 2830, 1820, 1800, 1710, 1635, 1585, 1570, 1480, 1460, 1440, 1415, 1370, 1350, 1300, 1260, 1205, 1145, 1100, 950, 735, 695, .sup.1 H NMR (400 MHz,CDCl.sub.3) .delta.8.09 (d, J=8.12 Hz, 2H), 8.00 (d, J=8.26 Hz, 2H) 7.66 (m, 4H), 7.59 (d=J=6.74 Hz,4H), 7.56 (t, J=7.27 Hz, 1H), 7.30-7.50 (m,22H) 7.16-7.26 (m, 10H) 7.09 (m,2H), 6.99 (t, J=7.59 Hz, 2H) 6.89 (t, J=7.97 Hz, 1H), 6.43 (d, J=6.08 Hz, 1H), 5.46 (bs, 1H), 5.38 (bs, iH), 5.35 (d, J=3.42 Hz, 1H), 4.89 (d, J=11.35 Hz, 1H), 4.75-4.80 (m, 4H), 4.72 (d, J=5.88 Hz, 2H), 4.69 (d, J=4.27 Hz, 2H), 4.36-4.55 (m, 5H), 4.28 (q, J=6.51 Hz, 1H), 4.17 (bd, J=5.46 Hz, 1H),3.90-4.00 (m,6H), 3.85 (d, J=2.99 Hz, 1H), 3.82 (d, J=2.89 Hz, 1H), 3.56-3.78 (m, 4H), 1.07 (m, 24H); HRMS (FAB): calcd for C.sub.99 H.sub.106 O.sub.20 Si.sub.2 Na 1694.6740 found 1694.6787. 6a: 230 mg (0.12 mmol) of iodosulfonamide 4a was azeotroped 5 times with dry benzene and placed under high vacuum for two hours. Added 2.4 ml of THF solution of 15 eq. of tin ether 9a (generated by azeotrophic removal of water overnight with a Dean-Stark trap equipped with freshly activated 4A mol. sieves from 561 mg (1.80 mmol) of 6a-TIPS-galactal and 673 .mu.l (1.32 mmol) bis(tributylin) oxide in 80 ml of benzene). To this solution stirring under an argon atmosphere was added 200 mg of freshly activated 4A powdered molecular sieves. Stirred one hour at room temperature. Cooled solution to -78.degree. C. and added, via cannula, a solution of 187 mg (0.96 mmol) of silver tetrafluroborate in 2.4 ml of THF. Warmed to room temperature over 15 hours and quenched the reaction, which had turned bright yellow, with 2 ml. of sat. bicarbonate. The reaction mixture was filtered through a pad of celite into a separatory funnel. The celite pad was washed thoroughly with ethyl acetate. The organics were washed twice with sat. bicarbonate and twice with sat. brine. The organics were dried over MgSO.sub.4. Concentration and chromatography in 25% ethyl acetate/hexanes gave 193 mg (75%) as a white foam 6a: [.alpha.].sub.D -126.4.degree. (c,505, CHCl.sub.3), IR (thin film) 3500, 3040, 3000, 2905, 2840, 1820, 1800, 1705,1635, 1590, 1440, 1410, 1255, 1195, 1100, 1080, 1035, 815, 730, 695; .sup.1 H NMR (400 MHz, CDCl.sub.3) .delta.8.09 (app t, 4H), 7.08-7.65 (m, 46H), 6.90 (t, J=7.65 Hz, 3H), 6.76 (d, J=6.91 Hz, 2H), 6.12 (d, J=6.59 Hz, 1H), 5.50 (bs 1H), 5.45 (bs 1H), 5.28 (app t, 2H), 3.03-4.91 (m, 36H), 1.09 (m, 45H); LRMS (FAB): cald for C.sub.120 H.sub.141 NO.sub.26 SSi.sub.3 Na 2153 found 2153. A Strategy for the Assembly of Complex, Branched Oligosaccharide Domains on a Solid Support: An Application to a Concise Synthesis of the Lewis.sup.b Domain in Bioconjugatable Form. The assembly of the Le.sup.b (type 1) domain is a relatively more difficult undertaking than was the Le.sup.y (type 2) target, wherein lactal was used as a convenient starting material. In the case of the type 1 determinant, lactal is not a useful starting material. The synthesis of the Le.sup.b system offered an opportunity to apply the polymer-based oligosaccharide construction method. (S. J. Danishefsky, K. F. McCLure, J. T. Randolph, R. B. Ruggeri, Science 1993, 260, 1307) The strategy is summarized in FIG. 4, wherein polymer-bound glycal 1 is activated for glycosyl donation via direct formation of a 1,2-anhydro derivative 2. Reaction of 2 with acceptor glycal 3 furnishes 4. Reiteration is achieved by means of direct epoxidation and reaction with acceptor 3. The self-policing nature of the method and the simple "one time" purification at the end of the synthesis are useful features. The present invention discloses an important additional dimension of the polymer-bound method. The logic is captured by inspection of FIG. 5. Each glycosylation event generates a unique C.sub.2 hydroxyl. In principle (and in fact, see infra) this hydroxyl can function as a glycosyl acceptor upon reaction with a solution based donor. The glycal linkage of 5, still housed on the support, can be further elongated. In this way, branching at C.sub.2 is accomplished while minimizing the requirement for protecting group machinations. (For an application of this strategy in the synthesis of a complex saponin, see: J. T. Randolph, S. J. Danishefsky, J. Am Chem Soc. 1993, 115, 8473) In principle, this branching can be implemented at any site in a growing chain. For such an extension, it would be necessary to cap all previously generated hydroxyl groups generated on the "polymer side" (non-reducing end) of the growing domain. Thus, the polymer-bound oligosaccharide can serve as either donor or acceptor, wherever appropriate. Initial efforts at reduction to practice identified tetrasaccharide glycal 6, bearing H-type 2 blood group specificity, as a goal. Polymer-supported galactal 7 (using as polymer support polystyrene crosslinked with 1% divinylbenzene functionalized using published procedures: T-H. Chan, W.-Q. Huang, J. Chem. Soc., Chem. Commun. 1985, 909; M. J. Farrall. J. M. J. Frechet, J. Org. Chem 1976, 41, 3877) reacted with a solution of 3,3-dimethyldioxirane (R. W. Murray, R. Jeyaraman, J. Org. Chem. 1985, 50, 2847), to provide the corresponding 1,2-anhydrosugar glycosyl donor, which was treated with a solution of glucal derivative 8 in the presence of ZnCl.sub.2 to provide 9 (R. L. Halcomb, S. J. Danishefsky, J. Am. Chem Soc. 1989, 111, 6661) This polymer-bound disaccharide acted as a glycosyl acceptor upon treatment with a solution of fucosyl fluoride 10 (K. C. Nicoloau, C. W. Hummel, Y. Iwabuchi, J. Am. Chem. Soc. 1992, 114, 3126) in the presence of Sn(OTf).sub.2 thereby giving 11. Retrieval of the trisaccharide glycal from the support was accomplished using tetrabutylammonium fluoride (TBAF) to afford 12 in 50% overall yield from 7. The trisaccharide, retrieved from the polymer, could then be further elaborated. Toward this end, compound 12 was converted to silyl ether 13 by reaction with TIPSCl. The latter was converted to the iodosulfonamide derivative 14 by the action of I(coll).sub.2 ClO.sub.4 in the presence of PhSO.sub.2 NH.sub.2. Reaction of 14 with galactal stannyl ether derivative 15 in the presence of AgBF.sub.4 gave 16 77% yield. (D. A. Griffith, S. J. Danishefsky, J. Am. Chem Soc. 1990, 112, 5811) Tetrasaccharide glycal 16 was deprotected and peracetylated to afford 6. (S. J. Danishefsky, K. Koseki, D. A. Griffith, J. Gervay, J. M. Peterson, F. E. MsDonald, T. Oriyama, J. Am. Chem Soc. 1992, 114, 8331) Thus, the synthesis of the full H-type determ | |||||||||||||||||||||||||||||||||||||||||||||