Synthesis and Biological Evaluation of 2-Fluoro-8-azaadenosine and Related Compounds

Academic Article

Abstract

  • The synthesis of 2-fluoro-8-azaadenosine (6e) and 2-amino-8-azaadenosine (6d) is described. Condensation of 9H-2,6-bis(methylthio)-8-azapurine (4) with 2,3,5-tri-O-acetyl-D-ribofuranosyl chloride (5) produces a mixture of 6a (9-β-D-ribofuranosyl) and 7a (8-β-D-ribofuranosyl). Standard functional group manipulation, including a modified Schiemann reaction to introduce the fluorine, allows preparation of 6d and 6e from the major isomer 6a. By a similar series of reactions the minor component 7a was converted to 7d and 7e, with the ribose ring attached at N-8 of the 8-azapurine ring system. Structure proofs utilized UV and 1H and 13C NMR data. Compounds 6b-e,g and 7b-f were evaluated in the H.Ep.-2 cell culture screen, and compounds 6c-e and 7d were evaluated in the P388 mouse leukemia screen. Adenosine deaminase data are also presented for some compounds. © 1983, American Chemical Society. All rights reserved.
  • Digital Object Identifier (doi)

    Author List

  • Montgomery JA; Shortnacy AT; Secrist JA
  • Start Page

  • 1483
  • End Page

  • 1489
  • Volume

  • 26
  • Issue

  • 10