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. 2019 Mar 1;25(13):3147-3155.
doi: 10.1002/chem.201803082. Epub 2018 Dec 13.

Rethinking Carbohydrate Synthesis: Stereoretentive Reactions of Anomeric Stannanes

Feng Zhu  1 , Sloane O'Neill  1 , Jacob Rodriguez  1 , Maciej A Walczak  1
Affiliations

Rethinking Carbohydrate Synthesis: Stereoretentive Reactions of Anomeric Stannanes

Feng Zhu et al. Chemistry. .

Abstract

In this Concept article, recent advances are highlighted in the synthesis and applications of anomeric nucleophiles, a class of carbohydrates in which the C1 carbon bears a carbon-metal bond. First, the advantages of exploiting the carboanionic reactivity of carbohydrates and the methods for the synthesis of mono- and oligosaccharide stannanes are discussed. Second, recent developments in the glycosyl cross-coupling method resulting in the transfer of anomeric configuration from C1 stannanes to C-aryl glycosides are reviewed. These highly stereoretentive processes are ideally suited for the preparation of carbohydrate-based therapeutics and were demonstrated in the synthesis of antidiabetic drugs. Next, the application of the glycosyl cross-coupling method to the preparation of Se-glycosides and to glycodiversification of small molecules and peptides are highlighted. 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 possibilities to incorporate saccharides into small molecules and biologics.

Keywords: carbohydrates; copper; cross-coupling; palladium; synthetic methods.

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Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Number of O-glycosylation reactions reported in SciFinder with various pyranosyl glycosyl donors categorized by the nature of the leaving groups (query on April 5, 2018).
Scheme 1.
Scheme 1.
(A) Classical displacement-based glycosylation methods. (B) Glycosyl cross-coupling method capitalizing on C1 nucleophiles.
Scheme 2.
Scheme 2.
Synthesis of anomeric stannanes.
Scheme 3.
Scheme 3.
(A) Selected debenzylation products obtained after the Birch reduction. (B) Physical form of 11a at ambient conditions, >1 g quantity. (C) Fully deprotected d-glucose stannane 13a.
Scheme 4.
Scheme 4.
Scope of C-aryl glycoside synthesis by glycosyl cross-coupling.
Scheme 5.
Scheme 5.
One-step synthesis of dapagliflozin. Reagents and conditions: (a) 14 (2 equiv), L4 (20 mol %), Pd2(dba)3 (5 mol%), CuCl (3 equiv), KF (2 equiv), 1,4-dioxane, 110°C, 72 h. (b) 13a (2 equiv), JackiePhos (20 mol%), Pd2(dba)3 (5 mol%), CuCl (3 equiv), KF (2 equiv), 1,4-dioxane, 110°C, 72 h.
Scheme 6.
Scheme 6.
Selected bioactive selenoglycosides and applications of Se-glycosides as glycosyl donors.
Scheme 7.
Scheme 7.
Scope of Se-glycoside synthesis by glycosyl cross-coupling.
Scheme 8.
Scheme 8.
Synthesis of Se-glycopeptides.
Scheme 9.
Scheme 9.
Proposed mechanism of stereoretentive Se-coupling.
See this image and copyright information in PMC

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