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Synthesis and biological evaluation of 2-fluoro-8-azaadenosine and related compounds

1983; American Chemical Society; Volume: 26; Issue: 10 Linguagem: Inglês

10.1021/jm00364a023

1520-4804

John A. Montgomery, Anita T. Shortnacy, John A. Secrist,

Fluorine in Organic Chemistry

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-beta-D-ribofuranosyl) and 7a (8-beta-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.