Heterocyclic analogs of nucleosides: synthesis and biological evaluation of novel analogs of puromycin

The diastereomeric 1-(piperidin-3′-yl)uracil compounds 20a, b, and the N6-dimethyl-9-(piperidin-3′-yl)adenine compounds 21a, b, have been prepared as analogs of the naturally occurring aminoacyl nucleoside antibiotic puromycin. The diastereomers were separated using high-pressure liquid chromatography, and the absolute configuration of the more mobile diastereomer 20a was assigned as (3′S,5′R) by 1H and 13C nuclear magnetic resonance analysis, and by molecular modelling. Therefore, the less mobile diastereomer 20b had the (3′R,5′S) configuration. The configurations of 21a and 21b were assigned by analogy with 20a and 20b. These puromycin analogs have been tested for anti-HIV and antitumor activity in vitro.