Synthesis and Biological Evaluation of 9-adenine and 9-adenine: Potential Neutral Precursors of 9-adenine 5'-Monophosphate

Article abstract of DOI:10.1021/jm00147a043

9-<5'-(2-Oxo-1,3,2-oxazaphosphorinan-2-yl)-β-D-arabinosyl>adenine (1c) and 9-<5'-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-β-D-arabinosyl>adenine (1d) were synthesized by reaction of 9-<β-D-arabinofuranosyl>adenine with phosphoryl chloride with 1-amino-3-propanol and 1,3-propanediol, respectively. 1c consisted of a mixture of diastereoisomers, while 1d was enantiomerically homogeneous.The structures of these compounds were established by spectral (1H NMR, MS, UV) and elemental analyses.Both 1c and 1d were resistant to degradation by 5'-nucleotidase, alkaline phosphatase, venom phosphodisterase, crude snake venom, adenosine deaminase ,and adenylate deaminase.Neither compound was significantly biotransformed by mouse hepatic microsomal preparations in the presence of an NADPH-generating system.Compound 1c was marginally effective at prolonging the life span of mice bearing P-388 leukemia; compound 1d, however, was inactive.