Enantioselective synthesis of antibiotic inducing gamma-butenolides from Streptomyces rochei and derivatives

Abstract

Given the challenges of discovering new natural products, further investigations into the regulatory systems that control their production are needed. Herein, we describe an enantioselective, divergent synthesis of two known autoregulators from Streptmyces rochei, the Streptomyces rochei butenolides (SRBs), which regulate production of the antibiotics lankacidin and lankamycin. The synthesis hinges on two key reactions: enantioselective alkynylation and regioselective photo-oxidation. The synthetic route also enabled access to nine derivatives, allowing for structure activity relationship studies. Specifically, we developed a quantitative green-fluorescence protein (GFP) based reporter assay and used this assay to assess key structural features for natural product induction in Streptomyces rochei.