Enantioselective Synthesis of Natural Trinorsesquiterpene Tetralones by Chemo-enzymatic Approaches

Abstract

The enantioselective syntheses of both the enantiomeric forms of the four natural tetralones 1a-d are here described. The aforementioned trinorsesquiterpenes were prepared starting either from substituted (S)-3-arylbutanols 5a-c or from substituted (S)-2-arylpropanols 7a-c. The latter chiral building blocks were in turn obtained through two different kinds of enzymatic transformations consisting of the baker's yeast mediated reduction of substituted (E)-3-aryl-but-2-enals 4a-c and the lipase-mediated resolution of racemic 2-arylpropanols 7a-c, respectively. Further key steps of the presented syntheses were C₁ and C₂ homologation procedures as well as the ring closure of the substituted 4-aryl-pentanoic acids 3a-c. By these means the target compounds were obtained in good yields and with very high stereoisomeric purity. In addition, the trinorsesquiterpene schiffnerone-B was synthesized for the first time and its absolute configuration was unambiguously assigned.