title: Highly stereocontrolled total synthesis of β-D-mannosyl phosphomycoketide: a natural product from Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, United States. nli@uchicago.edu
authors.forename: Nan-Sheng
authors.initials: NS
authors.lastname: Li
authors.forename: Louise
authors.initials: L
authors.lastname: Scharf
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Adams
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Piccirilli
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis*; D006017:Glycolipids / Q000138:chemical synthesis*; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D011422:Propionates / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D006017:Glycolipids; D011422:Propionates; C585644:beta-D-mannosyl phosphomycoketide