Regio- and Stereoselective Biocatalytic Monoamination of a Triketone Enables Asymmetric Synthesis of Both Enantiomers of the Pyrrolizidine Alkaloid Xenovenine Employing Transaminases

The (+)- as well as the (-)-enantiomer of the pyrrolizidine alkaloid xenovenine were prepared within five steps with 17 and 30% overall yields, respectively, in optically pure form, >99% ee as well as >99% de. In the asymmetric key step a transaminase performed a regio- and stereoselective mono-amination of a triketone. By employing two enantio-complementary transaminases from Arthrobacter sp. both enantiomers were accessible. The triketone was readily prepared via two steps starting from commercially available, achiral 2-(n-heptyl) furan. In the final catalytic hydrogenation step, the newly introduced chiral centre directed hydrogen addition to form preferentially the desired (5Z, 8E)-diastereomer. The regio- and stereoselective amination of a single ketone moiety out of three allowed the performance of the shortest and highest yielding total synthesis of the bicyclic showcase pyrrolizidine alkaloid without the need for protecting strategies.