Synthesis of deoxy and methoxy analogs of octyl alpha-D-mannopyranosyl-(1-->6)-alpha-D-mannopyranoside as probes for mycobacterial lipoarabinomannan biosynthesis

Carbohydr Res. 2007 Sep 3;342(12-13):1741-72. doi: 10.1016/j.carres.2007.05.001. Epub 2007 May 22.

Abstract

A panel of analogs of the disaccharide alpha-D-Manp-(1-->6)-alpha-D-Manp-OOctyl, a known acceptor substrate for a polyprenol monophosphomannose-dependent alpha-(1-->6)-mannosyltransferase involved in the assembly of the alpha-(1-->6)-linked mannan core of mycobacterial lipoarabinomannan, has been synthesized. Described are synthetic routes to the target deoxy and methoxy analogs in which one of the hydroxyl groups of the parent disaccharide has been modified. All glycosylation reactions involved the use of octyl glycoside acceptors and thioglycoside donors using iodonium-ion activation, and the stereochemistry of the mannopyranoside bond formed was established by measurement of the 1J(C-1,H-1). Depending on the target, the key methylation or deoxygenation reactions were carried out on either mono- or disaccharide substrates. This series of analogs will be useful for probing the substrate specificity of the enzyme, in particular, its steric and hydrogen-bonding requirements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / pharmacology
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Disaccharides / chemical synthesis
  • Disaccharides / chemistry*
  • Humans
  • Lipopolysaccharides / biosynthesis
  • Lipopolysaccharides / chemical synthesis
  • Lipopolysaccharides / chemistry*
  • Mannosides / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Mycobacterium tuberculosis / drug effects
  • Phosphatidylinositols / chemistry
  • Tuberculosis / drug therapy

Substances

  • Antitubercular Agents
  • Disaccharides
  • Lipopolysaccharides
  • Mannosides
  • Phosphatidylinositols
  • lipoarabinomannan