Synthesis of Antifungal Glucan Synthase Inhibitors from Enfumafungin

An efficient, new, and scalable semisynthesis of glucan
synthase
inhibitors 1 and 2 from the fermentation
product enfumafungin 3 is described. The highlights of
the synthesis include a high-yielding ether bond-forming reaction
between a bulky sulfamidate 17 and alcohol 4 and a remarkably chemoselective, improved palladium­(II)-mediated
Corey-Yu allylic oxidation at the highly congested C-12 position of
the enfumafungin core. Multi-hundred gram quantities of the target
drug candidates 1 and 2 were prepared, in
12 linear steps with 25% isolated yield and 13 linear steps with 22%
isolated yield, respectively.