Total Synthesis of Abyssomicin C and atrop-Abyssomicin C

摘要

Abyssomicin C (1) is a recently discovered antibiotic with a novel molecular architecture and unique mechanism of action. Isolated from the actinomycete Verrucosispora strain AB 18-032 cultivated from a sediment sample collected from the depths of the Sea of Japan, this deftly named natural product inhibits the biosynthesis of p-aminobenzoic acid in bacteria, a pathway that is absent in human physiology. The intriguing structural topology of abyssomicin C coupled with its reported activity against both methicillin-resistant Staph-ylococcus aureus (MRSA, 4 mu gmL~(-1)) and vancomycin-resist-ant Staphylococcus aureus (VRSA, 13 mu gmL~(-1)) prompted immediate interest from the synthetic community, culminating in a total synthesis by Sorensen and co-workers and several approaches toward its structure by a number of other groups. Herein, we report our efforts in this field which led not only to a total synthesis of abyssomicin C (1) but also to the recognition of atrop-abyssomicin C (2), a novel isomer of the naturally occurring product 1 that exhibits even more potent antibiotic activity than its originally isolated twin.