No abstract

An efficient and versatile protocol for the synthesis of C4‐acyl‐tetrofuranosides and C5‐acyl‐pentopyranosides has been established via the Liebeskind‐Srogl cross‐coupling reaction of various uronic acid‐derived thioesters and a wide range of arylboronic acids. Distinctive features of this transformation include mild reaction conditions, broad substrate scopes, impressive compatibility with a wide array of functional groups, and retention of stereochemical configurations. Dapagliflozin‐derived thioester is also amenable to this transformation, demonstrating the potential of this strategy in the late‐stage modifications of the active pharmaceuticals.

Comprehensive SummaryL‐Hexoses are key components of many biologically relevant natural products and pharmaceuticals. As rare sugars, L‐hexoses are not readily obtained from natural sources. Access to L‐hexose building blocks from commercially available and inexpensive D‐sugars is highly desirable from the viewpoints of organic synthesis and drug discovery. As demonstrated by the convenient preparation of L‐glucosyl, L‐galactosyl, and L‐mannosyl fluorides from readily available β‐D‐C‐glucosyl, β‐D‐C‐mannosyl, and β‐D‐C‐galactosyl derivatives, we describe a novel and efficient approach to the demanding L‐glycosyl fluorides. The transformation features the installation of anomeric hydroxymethyl group under mild conditions and C1‐to‐C5 switch of sugar rings through radical decarboxylative fluorination of uronic acids. The power of this protocol is highlighted by the first assembly of a pentasaccharide repeating unit of Pseudomonas ATCC 31554 extracellular polysaccharide (S‐88). This synthesis relies on the efficient extension of sugar chain at the sterically hindered hydroxy group and the facile introduction of L‐mannosyl unit using L‐mannosyl fluoride as glycosylating agent. The methods developed in this work would provide new tools to the arsenal of synthesis of L‐sugar building blocks and of assembly of glycans containing L‐sugar moieties.This article is protected by copyright. All rights reserved.

No abstract

L-Hexoses are key components of many biologically relevant natural products and pharmaceuticals. As rare sugars, L-hexoses are not readily obtained from natural sources. Access to L-hexose building blocks from commercially available and inexpensive D-sugars is highly desirable from the viewpoints of organic synthesis and drug discovery. As demonstrated by the convenient preparation of L-glucosyl, L-galactosyl, and L-mannosyl fluorides from readily available β-D-C-glucosyl, β-D-C-mannosyl, and β-D-C-galactosyl derivatives, we describe a novel and efficient approach to the demanding L-glycosyl fluorides. The transformation features the installation of anomeric hydroxymethyl group under mild conditions and head-to-tail inversion of sugar rings through radical decarboxylative fluorination of uronic acids. The power of this protocol is highlighted by the first assembly of a pentasaccharide repeating unit of Pseudomonas ATCC 31554 extracellular polysaccharide (S-88). This synthesis relies on the efficient extension of sugar chain at the sterically hindered hydroxy group and the facile introduction of L-mannosyl unit using L-mannosyl fluoride as glycosylating agent. The methods developed in this work would provide new tools to the arsenal of synthesis of L-sugar building blocks and of assembly of glycans containing L-sugar moieties.