Total synthesis of herbimycin A

Abstract

Benzoquinone ansamycin antibiotic herbimycin A was synthesized in 19 linear steps and 4.2% yield. Highlighted is the design of a chiral γ-lactone as the C11-C15 synthon that enabled a facile catalytic asymmetric synthesis of the challenging C8-C20 fragment of the target molecule. The easy access to the stereogenic centers and high overall yield made the strategy applicable in the molecular editing of benzoquinone ansamycins.