Evolution of a Reagent-Controlled Strategy for β-Selective C-Glycoside Synthesis

Abstract

Abstract C-Alkyl glycosides represent an attractive class of nonhydrolyzable carbohydrate mimetics which possess enormous potential as next-generation therapeutics. Methods for the direct stereoselective synthesis of C-alkyl glycosides with a broad substrate tolerance are limited, however. This is especially in the case of β-linked C-alkyl glycosides, where direct methods for synthesis from commonly available coupling partners remain limited. This Account describes the evolution of our laboratory’s studies on glycosyl sulfonate chemistry from a method for the construction of simple β-linked 2-deoxy-sugars to a technology for the direct synthesis of β-linked acyl and homoacyl glycosides that can be elaborated into more complex structures.1 Introduction2 Glycosyl Sulfonates3 Glycosyl Sulfonates in Oligosaccharide Synthesis4 Matching Donor and Sulfonate Reactivity5 β-Linked C-Acyl and Homoacyl Glycoside Synthesis6 Elaboration to other Products7 Conclusion