4'-modified analogues of aristeromycin and neplanocin A: synthesis and inhibitory activity toward S-adenosyl-L-homocysteine hydrolase

J Med Chem. 1992 May 15;35(10):1782-91. doi: 10.1021/jm00088a013.


The carbocyclic adenosine analogues aristeromycin and neplanocin A both display significant S-adenosyl-L-homocysteine (AdoHcy) hydrolase inhibitory activity and broad-spectrum antiviral effects. Since phosphorylation of the 4'-hydroxymethyl substituent has been implicated with the cytotoxicity of these compounds, various analogues modified at this position were synthesized utilizing a key cyclopentenone intermediate 3 which can be derived from several members of the natural chiral pool. Cyclopentenone 3 underwent a highly stereoselective conjugate addition with organocuprate reagents, and the 1,4-adducts so formed were then readily elaborated to the corresponding 4'-modified aristeromycin analogues. Alternatively, quenching the enolate intermediate of the organocuprate conjugate addition with methanesulfinyl chloride followed by pyrolytic syn elimination resulted in the formation of 4'-modified neplanocin A intermediates. Three of the final compounds (1b, 1c, and 1e) displayed inhibitory activity toward AdoHcy hydrolase in the nanomolar range.

Publication types

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

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemical synthesis
  • Adenosine / metabolism
  • Adenosine / pharmacology
  • Adenosylhomocysteinase
  • Animals
  • Cattle
  • Hydrolases / antagonists & inhibitors*
  • Liver / enzymology
  • Phosphorylation


  • aristeromycin
  • neplanocin A
  • Hydrolases
  • Adenosylhomocysteinase
  • Adenosine