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Macrocyclic bis-thioureas catalyze stereospecific glycosylation reactions

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Science  13 Jan 2017:
Vol. 355, Issue 6321, pp. 162-166
DOI: 10.1126/science.aal1875

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A cyclic catalyst to pair up sugars

Linking sugar molecules together to make complex carbohydrates is a geometrical challenge. For a six-carbon sugar such as glucose, there are six different possible linkage sites and also two possible configurations in which to anchor the incipient bond. Park et al. developed a ring-shaped, dimeric catalyst that pairs sugars after one of them has been modified with a chloride. The thiourea-based catalyst appears to pull away the chloride while simultaneously activating the incoming second sugar. The resultant bond-forming process reliably inverts the initial C–Cl configuration.

Science, this issue p. 162

Abstract

Carbohydrates are involved in nearly all aspects of biochemistry, but their complex chemical structures present long-standing practical challenges to their synthesis. In particular, stereochemical outcomes in glycosylation reactions are highly dependent on the steric and electronic properties of coupling partners; thus, carbohydrate synthesis is not easily predictable. Here we report the discovery of a macrocyclic bis-thiourea derivative that catalyzes stereospecific invertive substitution pathways of glycosyl chlorides. The utility of the catalyst is demonstrated in the synthesis of trans-1,2-, cis-1,2-, and 2-deoxy-β-glycosides. Mechanistic studies are consistent with a cooperative mechanism in which an electrophile and a nucleophile are simultaneously activated to effect a stereospecific substitution reaction.

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