Li, Nan-Sheng Scharf, Louise Adams, Erin J. Piccirilli, Joseph A. Highly Stereocontrolled Total Synthesis of β‑d‑Mannosyl Phosphomycoketide: A Natural Product from <i>Mycobacterium tuberculosis</i> β-d-Mannosyl phosphomycoketide (<b>C</b><sub><b>32</b></sub><b>-MPM</b>), a naturally occurring glycolipid found in the cell walls of <i>Mycobacterium tuberculosis</i>, acts as a potent antigen to activate T-cells upon presentation by CD1c protein. The lipid portion of <b>C</b><sub><b>32</b></sub><b>-MPM</b> contains a <b>C</b><sub><b>32</b></sub><b>-mycoketide</b>, 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 (2<i>S</i>)-3-hydroxy-2-methylpropionate (>99% ee). Our approach is the first highly stereocontrolled method to prepare <b>C</b><sub><b>32</b></sub><b>-MPM</b> 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. tuberculosis;Mycobacterium;ee;CD 1c protein;approach;method;lipid;olefination;stereocontrolled;stereopurity;chiral methyl branches;oligoisoprenoid chain 2013-06-21
    https://acs.figshare.com/articles/journal_contribution/Highly_Stereocontrolled_Total_Synthesis_of_d_Mannosyl_Phosphomycoketide_A_Natural_Product_from_i_Mycobacterium_tuberculosis_i_/2403055
10.1021/jo4006602.s001