Pot-Economical Total Synthesis of Clinprost

Org Lett. 2020 Dec 4;22(23):9365-9370. doi: 10.1021/acs.orglett.0c03616. Epub 2020 Nov 24.

Abstract

The pot-economical synthesis of clinprost is reported, in which the core bicyclo[3.3.0]octenone structure was synthesized by two key steps: an asymmetric domino Michael/Michael reaction catalyzed by diphenylprolinol silyl ether and an intramolecular Horner-Wadsworth-Emmons reaction. The trisubstituted endocyclic alkene was selectively introduced by 1,4-reduction followed by trapping of the generated enolate with Tf2NPh and subsequent utilization of the Suzuki-Miyaura coupling reaction. Chiral, nonracemic clinprost was synthesized in seven pots with a 17% total yield and excellent enantioselectivity.

Publication types

  • Research Support, Non-U.S. Gov't