Chemoenzymatic asymmetric total synthesis of phosphodiesterase inhibitors: preparation of a polycyclic pyrazolo[3,4-d]pyrimidine from an acylnitroso Diels-Alder cycloadduct-derived aminocyclopentenol.
[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.
Jiang
May Xiao-Wu
MX
Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556-5670, USA.
Warshakoon
Namal C
NC
Miller
Marvin J
MJ
D003517:Cyclopentanes / Q000737:chemistry*; D004798:Enzymes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared
D003517:Cyclopentanes; D004798:Enzymes; D010726:Phosphodiesterase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C016327:cyclopentanol; C014175:pyrazolo(3,4-d)pyrimidine