Abyssomicin C (1) is a recently discovered antibiotic with a novel molecular architecture and unique mechanism of action. [1] 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 Staphylococcus aureus (MRSA, 4 mg mL Γ1 ) and vancomycin-resistant Staphylococcus aureus (VRSA, 13 mg mL Γ1 ) prompted immediate interest from the synthetic community, culminating in a total synthesis by Sorensen and co-workers [2] and several approaches toward its structure by a number of other groups. [3] 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.
Aiming for maximum molecular diversity in the subsequent construction of analogues, our strategy for the total synthesis of the abyssomicins was based on the highly convergent retrosynthetic analysis depicted in Figure 1.