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

• Main Authors: Ding, Han, Lv, Jian, Zhang, Xiao-Lin, Xu, Yuan, Zhang, Yu-Han, Liu, Xue-Wei
• Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
• Format: Article
• Language: English
• Published: 2024
• Subjects: Chemistry; Donor-acceptor cyclopropanes; Glycosyl donors
• Online Access: https://hdl.handle.net/10356/174864
• Institution: Nanyang Technological University

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.