Enantioselective total synthesis of pyrrolo-[2,1-c][1,4]-benzodiazepine monomers (S)-(−)-barmumycin and (S)-(+)-boseongazepine B

Abstract

An efficient enantioselective total synthesis of pyrrolo-[2,1-c][1,4]benzodiazepine (PBD) monomers (S)-(−)-barmumycin and (S)-(+)-boseongazepine B and collective formal total syntheses of oxoprothracarcin, prothracarcin and (S)-(+)-boseongazepine C are described. The present approach is based on an efficient construction of an ethylidene substituted C-4 pyrrolidine core, that is the stereocontrolled introduction of a trisubstituted double bond through simple enolate α-alkylation of an ester, which also relies on a proline catalysed asymmetric α-amination followed by HWE olefination. The present synthetic route possesses superior stereocontrol over the C-4 ethylidene substituent as well as the C-(S) stereogenic center, which allows more functional variations on the five-membered prolinol core as compared to the existing PBD synthesis.