Highly stereocontrolled total synthesis of β-D-mannosyl phosphomycoketide: a natural product from Mycobacterium tuberculosis

J Org Chem. 2013 Jun 21;78(12):5970-86. doi: 10.1021/jo4006602. Epub 2013 Jun 11.


β-D-mannosyl phosphomycoketide (C32-MPM), a naturally occurring glycolipid found in the cell walls of Mycobacterium tuberculosis, acts as a potent antigen to activate T-cells upon presentation by CD1c protein. The lipid portion of C32-MPM contains a C32-mycoketide, consisting of a saturated oligoisoprenoid chain with five chiral methyl branches. Here we develop several stereocontrolled approaches to assemble the oligoisoprenoid chain with high stereopurity (>96%) using Julia-Kocienski olefinations followed by diimide reduction. By careful choice of olefination sites, we could derive all chirality from a single commercial compound, methyl (2S)-3-hydroxy-2-methylpropionate (>99% ee). Our approach is the first highly stereocontrolled method to prepare C32-MPM molecule with >96% stereopurity from a single >99% ee starting material. We anticipate that our methods will facilitate the highly stereocontrolled synthesis of a variety of other natural products containing chiral oligoisoprenoid-like chains, including vitamins, phytol, insect pheromones, and archaeal lipids.

MeSH terms

  • Biological Products / chemical synthesis*
  • Glycolipids / chemical synthesis*
  • Mycobacterium tuberculosis / chemistry*
  • Propionates / chemistry
  • Stereoisomerism


  • Biological Products
  • Glycolipids
  • Propionates
  • beta-D-mannosyl phosphomycoketide