Stereocontrolled\nSynthesis of (−)-Bactobolin\nA

Abstract

A stereoselective\nsynthesis of the ribosome-binding antitumor antibiotic\n(−)-bactobolin A is reported. The presented approach makes\neffective use of (−)-quinic acid as a chiral pool starting\nmaterial and substrate stereocontrol to establish the five contiguous\nstereocenters of (−)-bactobolin A. The key steps of the synthesis\ninclude a stereoselective vinylogous aldol reaction to introduce the\nunusual dichloromethyl substituent, a completely diastereoselective\nrhodium­(II)-catalyzed C–H amination reaction to set the configuration\nof the axial amine, and an intramolecular alkoxycarbonylation to build\nthe bicyclic lactone framework. The developed synthetic route was\nused to prepare 90 mg of (−)-bactobolin A trifluoroacetate\nin 10% overall yield.