Stereoselective total synthesis of cytotoxic cyclodepsipeptide menominin B: call for revision of the proposed structure

Abstract

The stereoselective total synthesis of the proposed structure of menominin B is described. A convergent approach involving multi-ester coupling and peptide coupling, along with key reactions such as Evans aldol and Maruoka allylation reactions for generating new chiral centers, and finally the ring-closing metathesis (RCM) for obtaining the macrocyclic framework, is demonstrated. The structure of the synthetic menominin B was established through extensive COSY, and HMBC analysis and finally confirmed by X-ray diffraction data. Interestingly, the synthesized compound displayed potent anti-cancer activity with IC₅₀ values of 7.2 ± 0.32 μM and 11.6 ± 0.53 μM, respectively, when screened against human MB-231 and murine 4T1 TNBC cells. Discrepancies in optical rotation and especially the spectroscopic data of the key tetradecanoate fragment call for a re-investigation of the proposed structure.