Synthesis and biological evaluation of 9-[5'-(2-oxo-1,3,2-oxazaphosphorinan-2-yl)-beta-D-arabinosyl]ade nine and 9-[5'-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-beta-D-arabinosyl]ade nine: potential neutral precursors of 9-[beta-D-arabinofuranosyl]adenine 5'-monophosphate.
9-[5'-(2-Oxo-1,3,2-oxazaphosphorinan-2-yl)-beta-D-arabinosyl]adeni ne (1c) and 9-[5'-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-beta-D-arabinosyl]adeni ne (1d) were synthesized by reaction of 9-[beta-D-arabinofuranosyl]adenine with phosphoryl chloride with 1-amino-3-propanol and 1,3-propanediol, respectively. 1c consisted of a mixture of diastereomers, 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 phosphodiesterase, 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.
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D015720:5'-Nucleotidase; D000659:AMP Deaminase / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001088:Arabinonucleotides; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D004355:Drug Stability; D005260:Female; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000378:metabolism; D009708:Nucleotidases / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000378:metabolism* / Q000627:therapeutic use; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use; D001084:Vidarabine Phosphate
D001088:Arabinonucleotides; D009943:Organophosphorus Compounds; D001084:Vidarabine Phosphate; C046491:9-(5'-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-beta-arabinosyl)adenine; C046490:9-(5'-(2-oxo-1,3,2-oxazaphosphorinan-2-yl)-beta-arabinosyl)adenine; D009708:Nucleotidases; D000469:Alkaline Phosphatase; D015720:5'-Nucleotidase; D010727:Phosphoric Diester Hydrolases; D000243:Adenosine Deaminase; D000659:AMP Deaminase; D014740:Vidarabine