Asymmetric total synthesis of epolactaene. Part 1: Construction of epoxy-γ-lactam moiety and deduction of absolute stereochemistry

Abstract

Enantioselective construction of the epoxy-γ-lactam moiety of epolactaene (1) was completed in 11 steps from (R)-lactaldehyde derivatives. Key steps include: (i) the stereoselective aldol reaction between (R)-lactaldehyde and malonate ester; (ii) diastereospecific lactonization of malonate ester derivative 10; (iii) cyclization of 16 to epoxy-γ-lactam derivative 2. Both enantiomers, (R,R)-2 and (S,S)-2, were synthesized, and their optical rotations were compared with that of (+)-epolactaene (1). The results suggest that the absolute configuration of 1 is (13R,14R).