Rh(I)-Catalyzed Allenic Pauson-Khand Reaction to Access the Thapsigargin Core: Influence of Furan and Allenyl Chloroacetate Groups on Enantioselectivity

Org Lett. 2022 Feb 4;24(4):995-999. doi: 10.1021/acs.orglett.1c03951. Epub 2022 Jan 26.

Abstract

Thapsigargin (Tg) is a potent SERCA pump inhibitor with the potential to treat cancer and COVID-19. We have extended the scope of the asymmetric allenic Pauson-Khand reaction to furan-tethered allene-ynes, a stereoconvergent transformation affording the 5,7,5-ring system of Tg in good yields and high enantioselectivity. Computational studies of the oxidative cyclization step show that the furan and chloroacetate groups contribute to this high selectivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • COVID-19 Drug Treatment
  • Catalysis
  • Chloroacetates / chemistry
  • Cyclization
  • Furans / chemistry
  • Models, Molecular
  • Molecular Structure
  • Rhodium / chemistry*
  • Stereoisomerism
  • Thapsia / chemistry
  • Thapsigargin / analogs & derivatives*
  • Thapsigargin / chemistry*

Substances

  • Chloroacetates
  • Furans
  • Thapsigargin
  • Rhodium