Combined Enzyme- and Transition Metal-Catalyzed Strategy for the Enantioselective Syntheses of Nitrogen Heterocycles: (-)-Coniine, DAB-1, and Nectrisine

Donald R Deardorff; Scott W Niman; Mark I Paulsen; Anasheh Sookezian; Meghan E Whalen; Christopher J Finlayson; Collrane Frivold; Hilary C Brown; Jeffrey S Cannon

doi:10.1021/acsomega.9b03990

Combined Enzyme- and Transition Metal-Catalyzed Strategy for the Enantioselective Syntheses of Nitrogen Heterocycles: (-)-Coniine, DAB-1, and Nectrisine

ACS Omega. 2020 Jan 23;5(4):2005-2014. doi: 10.1021/acsomega.9b03990. eCollection 2020 Feb 4.

Authors

Donald R Deardorff¹, Scott W Niman¹, Mark I Paulsen¹, Anasheh Sookezian¹, Meghan E Whalen¹, Christopher J Finlayson¹, Collrane Frivold¹, Hilary C Brown¹, Jeffrey S Cannon¹

Affiliation

¹ Department of Chemistry, Occidental College, 1600 Campus Rd. M-5, Los Angeles, California 90041, United States.

Abstract

The enantioselective syntheses of (-)-coniine, DAB-1, and nectrisine have been developed, utilizing a complementary strategy of enzyme- and transition metal-catalyzed reactions. The initial stereocenter was set with >99% enantioselectivity via an enzyme-catalyzed hydrocyanation reaction. Substrate incompatibilities with the natural enzyme were overcome by tactical utilization of ruthenium-catalyzed olefin metathesis to functionalize an enzyme-derived (R)-allylic fragment. The piperidine and pyrrolidine alkaloid natural products were obtained by a route that leveraged regio- and stereoselective palladium-catalyzed 1,3-substitutive reactions.