One-Pot Assembly of Mannose-Capped Lipoarabinomannan Motifs up to 101-Mer from the Mycobacterium tuberculosis Cell Wall

被引：10

作者：

Ma, Yuxin ^{[1
]}

Zhang, Yunqin ^{[1
]}

Huang, Yingying ^{[1
,2
]}

Chen, Zixi ^{[1
,2
]}

Xian, Qingyun ^{[1
]}

Su, Rui ^{[1
]}

Jiang, Qiong ^{[2
]}

Wang, Xiufang ^{[2
]}

Xiao, Guozhi ^{[1
]}

机构：

[1] Univ Chinese Acad Sci, Chinese Acad Sci, State Key Lab Phytochem & Plant Resources West Chi, Kunming Inst Bot, Kunming 650204, Peoples R China

[2] Kunming Univ, Dept Chem, Kunming 650214, Peoples R China

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2024年 / 146卷 / 06期

基金：

中国博士后科学基金;

关键词：

POLYSACCHARIDE-RELATED OLIGOSACCHARIDES; STEREOSELECTIVE-SYNTHESIS; GLYCOSYLATION; DONORS; CHALLENGES; DISCOVERY; CATALYSIS;

D O I：

10.1021/jacs.3c12815

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Lipoarabinomannan (LAM) from the Mycobacterium tuberculosis cell envelope represents important targets for the development of new therapeutic agents against tuberculosis, which is a deadly disease that has plagued mankind for a long time. However, the accessibility of long, branched, and complex lipoarabinomannan over 100-mer remains a long-standing challenge. Herein, we report the modular synthesis of mannose-capped lipoarabinomannan 101-mer from the M. tuberculosis cell wall using a one-pot assembly strategy on the basis of glycosyl ortho-(1-phenylvinyl)benzoates (PVB), which not only accelerates the modular synthesis but also precludes the potential problems associated with one-pot glycosylation with thioglycosides. Shorter sequences including 18-mer, 19-mer, and 27-mer are also synthesized for in-depth structure-activity relationship biological studies. Current synthetic routes also highlight the following features: (1) streamlined synthesis of various linear and branched glycans using one-pot orthogonal glycosylation on the combination of glycosyl N-phenyltrifluoroacetimidates, glycosyl ortho-alkynylbenzoates, and glycosyl PVB; (2) highly stereoselective construction of 10 1,2-cis-arabinofuranosyl linkages using 5-O-(2-quinolinecarbonyl)-directing 1,2-cis-arabinofuranosylation via a hydrogen-bond-mediated aglycone delivery strategy; and (3) convergent [(18 + 19) x 2 + 27] one-pot synthesis of the 101-mer LAM polysaccharide. The present work demonstrates that this orthogonal one-pot glycosylation strategy can highly streamline the chemical synthesis of long, branched, and complex polysaccharides.

引用

页码：4112 / 4122

页数：11