jo4006602_si_001.pdf (11.19 MB)
Highly Stereocontrolled Total Synthesis of β‑d‑Mannosyl Phosphomycoketide: A Natural Product from Mycobacterium tuberculosis
journal contribution
posted on 2013-06-21, 00:00 authored by Nan-Sheng Li, Louise Scharf, Erin J. Adams, Joseph A. Piccirilliβ-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.