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Zinc(II) Iodide-Directed β-Mannosylation: Reaction Selectivity, Mode, and Application

Authors :
Jiaming Ao
Yan Huang
Wanmeng Zhu
Siai Zhou
Xue-Wei Liu
Akihiro Ishiwata
Aoxin Guo
Feiqing Ding
Xuemei Zhong
Qian Xiao
Yukishige Ito
Hui Cai
School of Physical and Mathematical Sciences
Source :
The Journal of Organic Chemistry. 86:16901-16915
Publication Year :
2021
Publisher :
American Chemical Society (ACS), 2021.

Abstract

A direct, efficient, and versatile glycosylation methodology promises the systematic synthesis of oligosaccharides and glycoconjugates in a streamlined fashion like the synthesis of medium to long-chain nucleotides and peptides. The development of a generally applicable approach for the construction of 1,2-cis-glycosidic bond with controlled stereoselectivity remains a major challenge, especially for the synthesis of β-mannosides. Here, we report a direct mannosylation strategy mediated by ZnI2, a mild Lewis acid, for the highly stereoselective construction of 1,2-cis-β linkages employing easily accessible 4,6-O-tethered mannosyl trichloroacetimidate donors. The versatility and effectiveness of this strategy were demonstrated with successful β-mannosylation of a wide variety of alcohol acceptors, including complex natural products, amino acids, and glycosides. Through iteratively performing ZnI2-mediated mannosylation with the chitobiosyl azide acceptor followed by site-selective deprotection of the mannosylation product, the novel methodology enables the modular synthesis of the key intermediate trisaccharide with Man-β-(1 → 4)-GlcNAc-β-(1 → 4)-GlcNAc linkage for N-glycan synthesis. Theoretical investigations with density functional theory calculations delved into the mechanistic details of this β-selective mannosylation and elucidated two zinc cations' essential roles as the activating agent of the donor and the principal mediator of the cis-directing intermolecular interaction. We thank the Fundamental Research Funds for the Central Universities (no. 31610011 to F.D.), the Province Natural Science Fund of Guangdong (no. 42030015 to F.D.), and the Sun Yat-sen University Startup Fund (no.18841224 to F.D.) for financial support and the grant-in-aid for Specially Promoted Research (no. 16H06290 to Y.I. and A.I.) and for Scientific Research (no.18K05345 and 19H00929 to A.I.) from the Japan Society for the Promotion of Science.

Details

ISSN :
15206904 and 00223263
Volume :
86
Database :
OpenAIRE
Journal :
The Journal of Organic Chemistry
Accession number :
edsair.doi.dedup.....2f2fb1be09ae085b745388942184970f