Reinvestigation of N,N‑Diacetylimido-Protected 2‑Aminothioglycosides in O‑Glycosylation: Intermolecular Hydrogen Bonds Contributing to 1,2-Orthoamide Formation

N,N-Diacetylimido protection of 2-aminoglycosides is an elegant strategy but has had limited applications due to unexpected side reactions in glycosylation. We found that high acid concentrations could diminish the side reactions. We observed intermolecular hydrogen bonding among alcohols and acids...

Full description

Saved in:
Bibliographic Details
Published in:Journal of organic chemistry 2021-10, Vol.86 (19), p.13212-13230
Main Authors: Shao, Liming, Huo, Zhenni, Lei, Na, Yang, Min, He, Zehuan, Zhang, Yongliang, Wei, Qinlong, Chen, Changsheng, Xiao, Mei, Wang, Fei, Gu, Guofeng, Cai, Feng
Format: Article
Language:English
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:N,N-Diacetylimido protection of 2-aminoglycosides is an elegant strategy but has had limited applications due to unexpected side reactions in glycosylation. We found that high acid concentrations could diminish the side reactions. We observed intermolecular hydrogen bonding among alcohols and acids could disrupt. Assuming that intermolecular hydrogen bonding accelerates the formation of 1,2-orthoamides and disrupting intermolecular hydrogen bonds could turn to the desired glycosylation, we successfully employed sulfenyl triflate pre-activation in the glycosylation of a broad scope of alcohol acceptors, as well as in a one-pot synthesis of a protected human milk oligosaccharide, lacto-N-neotetraose.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.1c01009