Formal Synthesis of Methylenomycin B

Abstract

Methylenomycin B is a simple compound isolated from culture broth of Streptomyces species.¹ Synthesis of the cyclopentenoid^1c,2 antibiotic must contend with its lability which originates from the α-methylene ketone moiety; it is thus mandatory to set the extracyclic double bond in place at the very last stage. From our retrosynthetic analysis we concluded that acyclic precursors containing an eliminable XY element at the α' and β' positions of the propanone fragment are advantageous, in which X is an electron-withdrawing group capable of directing regiospecific introduction. The methylenomycin B precursor, keto acid (5) was prepared from dimethyl maleate in four steps.