| Title: | Highly stereocontrolled total synthesis of beta-D-mannosyl phosphomycoketide: a natural product from Mycobacterium tuberculosis |
| Author(s): | Li NS; Scharf L; Adams EJ; Piccirilli JA; |
| Address: | "Department of Biochemistry and Molecular Biology, University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, United States. nli@uchicago.edu" |
| ISSN/ISBN: | 1520-6904 (Electronic) 0022-3263 (Linking) |
| Abstract: | "beta-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" |
| Keywords: | Biological Products/*chemical synthesis Glycolipids/*chemical synthesis Mycobacterium tuberculosis/*chemistry Propionates/chemistry Stereoisomerism; |
| Notes: | "MedlineLi, Nan-Sheng Scharf, Louise Adams, Erin J Piccirilli, Joseph A eng 2013/06/04 J Org Chem. 2013 Jun 21; 78(12):5970-86. doi: 10.1021/jo4006602. Epub 2013 Jun 11" |
