STEREOSPECIFIC VORBRUGGEN-LIKE REACTIONS OF 1,2-ANHYDRO SUGARS - AN ALTERNATIVE ROUTE TO THE SYNTHESIS OF NUCLEOSIDES

Recently we described the oxidative conversion of pyranose glycals to 1,2-anhydro sugars by reaction with 3,3-dimethyldioxirane (1).la While this class of compounds had been known for many years, 2 the general use of such epoxides as glycosylating agents was rather limited.3 With the advent of a straightforward method for the stereospecific synthesis of such systems came the encouragement to investigate the effects of resident protecting groups on the efficiency of 1,2-anhydropyranohexoses as glycal donors. It was found that in the presence of nonparticipating neighboring groups, systems such as 3 undergo inversion of configuration upon reaction with various alcohols, including secondary alcohols, in the presence of zinc chloride.1b In the work described herein, we addressed the question as to whether 1,2-anhydro sugars might glycosylate heterocyclic bases and, if so, what would be the stereoselectivity of such reactions. Given the useful role of nonnatural nucleosides in antiviral therapy4 the problem of providing stereospecific access to this series is of particular topical interest. © 1990, American Chemical Society. All rights reserved.