Rethinking Carbohydrate Synthesis: Stereoretentive Reactions of Anomeric Stannanes

Abstract

In this Concept article, we highlight recent advances in the synthesis and applications of anomeric nucleophiles, a class of carbohydrates in which the C1 carbon bears a carbon-metal bond. First, we discuss the advantages of exploiting the carboanionic reactivity of carbohydrates and the methods for the synthesis of mono- and oligosaccharide stannanes. Second, we discuss recent developments in the glycosyl cross-coupling method resulting in transfer of anomeric configuration from C1 stannanes to C-aryl glycosides. These highly stereoretentive processes are ideally suited for the preparation of and was demonstrated in the synthesis of antidiabetic drugs. Next, we highlight the applications of glycosyl cross-coupling method to the preparation of Se-glycosides and in glycodiversification of small molecules and peptides. These reactions proceed with exclusive anomeric control for a broad range of substrates and tolerate carbohydrates with free hydroxyl groups. Taken together, anomeric nucleophiles have emerged as powerful tools for the synthesis of oligosaccharides and glycoconjugates and their future applications will open new avenues to incorporate saccharides into small molecules and biologics.

Cross-Electrophile Coupling of 2-Iodoglycals Enables Efficient Access to 2-C-Glycals

“…As part of our continuing interest in carbohydrate synthesis, [21][22][23] we deemed it worthwhile to explore mild and modular C-C cross-coupling methods to access 2-C-aryl glycosides. Cross-electrophile coupling reactions have emerged as practical, environmentally friendly, efficient, and highly controllable approaches for constructing C-C bonds through selectively coupling various electrophiles.…”

Pd-Catalyzed Stereospecific Glycosyl Cross-Coupling of Reversed Anomeric Stannanes for Modular Synthesis of Nonclassical C-Glycosides

“…Transition metal-catalyzed glycosylation cross-coupling (GCC) reactions involving glycosyl nucleophiles representing a novel design strategy for glycosylation reactions. 51 In this context, we have successfully developed highly stereospecific cross-coupling reactions of both anomers of C1-stannanes with aryl halides catalyzed by Pd, enabling the precise synthesis of classical aryl C-glycosides. The method exhibits broad substrate scope, excellent functional group compatibility, and consistently high stereospecificity.…”

Acyl Glycosides through Stereospecific Glycosyl Cross-Coupling: Rapid Access to C(sp3)-Linked Glycomimetics

“…Herein, we report a new methodology for the programmed synthesis of C -glycosyl ketones capitalizing on a stereospecific cross-coupling reaction of anomeric stannanes − ,− with thio- and selenoesters, resulting in exclusive control of anomeric configuration for both anomers of various saccharides (Scheme D). We further demonstrate the utility of C -glycosyl ketones as important building blocks in the preparation of relevant C­(sp 3 )-glycomimetics using reductive and deoxyfluorination methods to afford several examples of CH 2 - and CF 2 -linked glycosides.…”