Catalytic asymmetric synthesis of an HIV integrase inhibitor

Org Lett. 2009 Jan 15;11(2):369-72. doi: 10.1021/ol802604v.

Abstract

An efficient synthesis of HIV integrase inhibitor (S)-(-)-1 via a unique asymmetric hydrogenation of a mixture of imines/enamine 5a-5b/5c is described. Hydrogenation of the imines/enamine by a Rh(I)-Josiphos complex afforded 6 in 90% yield and 90% ee. Amide formation completed the synthesis of 1 in 58% overall yield from 2, which is readily available from 3,4-dihydro-2H-pyran in a seven-step sequence. A deuterium labeling study suggests the asymmetric hydrogenation proceeds predominantly via the enamine tautomer.

MeSH terms

  • Amines / chemistry
  • Catalysis
  • HIV Integrase Inhibitors / chemical synthesis*
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase*
  • Hydrogenation
  • Imines / chemistry
  • Stereoisomerism

Substances

  • Amines
  • HIV Integrase Inhibitors
  • Imines
  • HIV Integrase