The Chemistry of Isopropenyl Glycopyranosides. Transglycosylations and Other Reactions H. Keith Chenault,* Alfredo Castro, Laura F. Chafin, and Jie Yang Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716 Received January 30, 1996 X Various anomerically pure isopropenyl R- and -glycopyranosides have been synthesized and shown to undergo synthetically useful transglycosylation reactions with a variety of primary and secondary carbohydrate alcohols. Although stable when stored, isopropenyl glycosides are readily activated as glycosyl donors by a variety of electrophiles, including N-iodosuccinimide/triflic acid, trimethylsilyl triflate, and triflic anhydride. Under conditions that retard formation of the glycosyl cation, the reactivity of isopropenyl glycosides is diverted away from transglycosylation and toward electrophilic addition across the vinyl ether double bond. Introduction Oligosaccharides and glycoconjugates play important roles in cellular development, adhesion, communication, migration, infection, and disease. 1,2 Work aimed at the preparation and study of these compounds has resulted in the development of a variety of new glycosylating agents. 2,3 Among those more recently introduced are thioglycosides, 4-6 glycosyl trichloroacetimidates, 7 glycosyl fluorides, 8-10 n-pentenyl glycosides, 11 glycosyl sulfoxides 12 and sulfones, 13 selenoglycosides, 14 and glycosyl phos- phites. 15 We and others have introduced the use of iso- propenyl 16,17 and other vinyl glycosides 18 as glycosyl donors. At the beginning of our work, we envisioned that isopropenyl glycosides would be activated as glycosyl donors by electrophiles in a manner similar to that already observed by Fraser-Reid and co-workers with n-pentenyl glycosides. 11 In fact, the expectation was that conjugation of the electrophilic double bond with the glycosidic oxygen would make isopropenyl glycosides even more reactive than n-pentenyl glycosides. The mecha- nism of activation was expected to involve initial capture of the electrophile (E + ) by the vinyl ether double bond of 1 leading to the formation of cation 2 or 3 (Scheme 1). Collapse of 2 or 3 to form glycosyl oxocarbenium cation 5 and acetone derivative 4 would be followed by nucleo- philic attack on 5 to generate glycoside 7. If the isopro- penyl glycoside contained an ester protecting group at C-2, neighboring-group participation would lead to the formation of a resonance-stabilized dioxocarbenium ion 6, which would then undergo nucleophilic attack to generate exclusively the 1,2-trans-glycoside (e.g., -glu- coside) 7. An alternative reaction would involve direct nucleophilic attack on 2 or 3 to generate the addition product 8. We describe here the stereoselective synthesis of a variety of isopropenyl R- and -glycopyranosides and the use of these compounds as glycosyl donors for oligosac- charide synthesis. The effects of varying the promoter, glycosyl donor, and glycosyl acceptor have been studied. It turns out that isopropenyl glycosides are poised delicately between two manifolds of reactivity. Solvent, promoter, and protecting groups on the glycosyl donor can direct the reactivity of isopropenyl glycosides toward either transglycosylation or electrophilic addition. Results and Discussion Synthesis of Isopropenyl Glycopyranosides. Re- action of bis(acetonyl)mercury 19 with glycopyranosyl halides 9a-f resulted in O-glycosylation 20 and produced the corresponding isopropenyl -glycopyranosides 10a-f X Abstract published in Advance ACS Abstracts, July 1, 1996. (1) (a) Glycobiology; Welply, J. K., Jaworski, E., Eds.; Wiley-Liss: New York, 1990; Vol. 3. (b) Neurobiology of Glycoconjugates; Margolis, R. U., Margolis, R. K., Eds.; Plenum: New York, 1989. (c) Rademacher, T. W.; Parekh, R. B.; Dwek, R. A. Ann. Rev. Biochem. 1988, 57, 785- 838. (d) Glycoconjugates; Horowitz, M. I., Ed.; Academic: New York, 1982; Vols. 3 and 4. (e) The Molecular Immunology of Complex Carbohydrates; Wu, A. M., Ed.; Plenum: New York, 1988. (f) Thiem, J. In Trends in Synthetic Carbohydrate Chemistry; Horton, D., Hawk- ins, L. D., McGarvey, G. J., Eds.; American Chemical Society: Wash- ington, DC, 1989; pp 131-149. (g) Shen, T. Y. Ann. N.Y. Acad. Sci. 1987, 507, 272-280. 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