Asymmetric Total Synthesis of (-)-(3R)-Inthomycin C

A short (10 step) and efficient (15% overall yield) synthesis of the natural product (-)-(3R)-inthomycin C is reported. The key steps comprise three C-C bond-forming reactions: (i) a vinylogous Mukaiyama aldol, (ii) an olefin cross-metathesis reaction, and (iii) an asymmetric Mukaiyama-Kiyooka aldol. This route is notable for its brevity and has the advantage of lacking stoichiometric tin promoted cross-coupling reactions present in previous approaches. Initial investigations on the biological activity of (-)-(3R)-inthomycin C and structural analogues on human cancer cell lines are also described for the first time.