Issue 10, 2024

Efficient O- and S-glycosylation with ortho-2,2-dimethoxycarbonylcyclopropylbenzyl thioglycoside donors by catalytic strain-release

Abstract

We herein present a strain-release glycosylation method employing a rationally designed ortho-2,2-dimethoxycarbonylcyclopropylbenzyl (CCPB) thioglycoside donor. The donor is activated through the nucleophilic ring-opening of a remotely activable donor–acceptor cyclopropane (DAC) catalyzed by mild Sc(OTf)3. Our new glycosylation method efficiently synthesizes O-, N-, and S-glycosides, providing facile chemical access to the challenging S-glycosides. Because the activation conditions of conventional glycosyl donors and our CCPB thioglycoside are orthogonal, our novel donor is amenable to controlled one-pot glycosylation reactions with conventional donors for expeditious access to complex glycans. The strain-release glycosylation is applied to the assembly of a tetrasaccharide of O-polysaccharide of Escherichia coli O-33 in one pot and the synthesis of a 1,1′-S-linked glycoside oral galectin-3 (Gal-3) inhibitor, TD139, to demonstrate the versatility and effectiveness of the novel method for constructing both O- and S-glycosides.

Graphical abstract: Efficient O- and S-glycosylation with ortho-2,2-dimethoxycarbonylcyclopropylbenzyl thioglycoside donors by catalytic strain-release

Supplementary files

Article information

Article type
Edge Article
Submitted
09 Dec 2023
Accepted
18 Jan 2024
First published
07 Feb 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2024,15, 3711-3720

Efficient O- and S-glycosylation with ortho-2,2-dimethoxycarbonylcyclopropylbenzyl thioglycoside donors by catalytic strain-release

H. Ding, J. Lv, X. Zhang, Y. Xu, Y. Zhang and X. Liu, Chem. Sci., 2024, 15, 3711 DOI: 10.1039/D3SC06619C

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