Total Synthesis of (−)-Mniopetal E, a Novel Biologically Intriguing Drimane Sesquiterpenoid

We have achieved the total synthesis of (−)-mniopetal E, a drimane sesquiterpenoid which inhibits the reverse transcriptase of human immunodeficiency virus (HIV)-1. Our enantiospecific total synthesis of this target molecule in naturally occurring form commenced with a known 2,3-anhydro-d-arabinitol derivative, which was prepared using the Sharpless asymmetric epoxidation strategy. The key steps of our total synthesis were as follows:  (1) a combination of highly stereocontrolled inter- and intramolecular Horner−Emmons carbon elongations for construction of a butenolide tethering a 1,2,4,9-functionalized nona-5,7-diene moiety at the β-carbon, (2) stereoselective thermal intramolecular Diels−Alder reaction of the thus-formed trienic compound, providing preferentially an endo-cycloadduct with the desired π-facial selection, and (3) efficient transformation of the γ-lactone moiety in the major cycloadduct to the γ-hydroxy-γ-lactone part in mniopetal E. Our total synthesis of (−)-mniopetal E established the unsettled absolute stereochemistry of the antibiotic.