Asymmetric total synthesis of (−)-rasfonin

Abstract

An efficient chemoenzymatic asymmetric synthesis of pyranone containing natural product (−)-rasfonin is presented here. Enantioselective enzymatic desymmetrization (EED) and a unique Gluconobacter oxydans mediated oxidative kinetic resolution (OKR) have been successfully employed to install three stereocenters (C6′, C7, and C9) of the target molecule. Stereoselective Achmatowicz reaction of a properly decorated furyl nucleus led to the core pyranone structure of rasfonin. At the late stage of the synthesis Negishi coupling has been used to complete the synthesis.