A General Strategy to Synthesize ADP-7-Azido-heptose and ADP-Azido-mannoses and Their Heptosyltransferase Binding Properties

Tianlei Li; Abdellatif Tikad; Huixiao Fu; Jozafina Milicaj; Colleen D Castro; Marine Lacritick; Weidong Pan; Erika A Taylor; Stéphane P Vincent

doi:10.1021/acs.orglett.1c00048

A General Strategy to Synthesize ADP-7-Azido-heptose and ADP-Azido-mannoses and Their Heptosyltransferase Binding Properties

Org Lett. 2021 Mar 5;23(5):1638-1642. doi: 10.1021/acs.orglett.1c00048. Epub 2021 Feb 23.

Authors

Tianlei Li^{1

2}, Abdellatif Tikad^{1

3}, Huixiao Fu¹, Jozafina Milicaj⁴, Colleen D Castro⁴, Marine Lacritick¹, Weidong Pan⁵, Erika A Taylor⁴, Stéphane P Vincent¹

Affiliations

¹ University of Namur, Département de Chimie, Laboratoire de Chimie Bio-Organique, rue de Bruxelles 61, B-5000 Namur, Belgium.
² State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100005, China.
³ Laboratoire de Chimie Moléculaire et Substances Naturelles, Faculté des Sciences, Université Moulay Ismail, B.P. 11201, Zitoune, Meknès, Morocco.
⁴ Department of Chemistry, Wesleyan University, Middletown, Connecticut 06459, United States.
⁵ State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.

PMID: 33620227
DOI: 10.1021/acs.orglett.1c00048

Abstract

The multistep synthesis of a novel ADP-7-azido-7-deoxy-l-glycero-β-d-manno-heptopyranoside 2a and several analogues as heptosyltransferase ligands is described. The synthesis of the key intermediate heptoside-1-β-phosphate 3a involved a β-stereoselective phosphorylation of lactol 4 employing diallyl chlorophosphate as a phosphorylating reagent. Five deprotected nucleotide sugars were generated by this synthetic sequence and evaluated as heptosyltransferase substrates (K_M, k_cat).

Publication types

Research Support, Non-U.S. Gov't