Chemoenzymatic asymmetric total synthesis of phosphodiesterase inhibitors: preparation of a polycyclic pyrazolo[3,4-d]pyrimidine from an acylnitroso Diels-Alder cycloadduct-derived aminocyclopentenol

J Org Chem. 2005 Apr 1;70(7):2824-7. doi: 10.1021/jo0484070.

Abstract

[reaction: see text] Enzymatic resolution of Boc-protected 4-aminocyclopenten-1-ol 4c gave both enantiomers 5c and 6c in high ee. Boc removal and separate condensation with chloropyrazolopyrimidine 18 provided elaborated 1,4-aminocyclopentenol derivatives 20 and 26, respectively. Separate treatment of 20 and 26 with Pd(0) under basic conditions induced cyclization to unsaturated polycycles 22 and 27, which, upon catalytic hydrogenation, were transformed to new cyclopentane-containing pyrazolopyrimidines 24 and 28, analogues of recently described novel phosphodiesterase inhibitors.

Publication types

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

MeSH terms

  • Cyclopentanes / chemistry*
  • Enzymes / chemistry*
  • Magnetic Resonance Spectroscopy
  • Phosphodiesterase Inhibitors / chemical synthesis*
  • Phosphodiesterase Inhibitors / chemistry
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Spectrometry, Mass, Fast Atom Bombardment
  • Spectrophotometry, Infrared

Substances

  • Cyclopentanes
  • Enzymes
  • Phosphodiesterase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • cyclopentanol
  • pyrazolo(3,4-d)pyrimidine