Carbocyclic analogues of xylofuranosylpurine nucleosides. Synthesis and antitumor activity.
(+/-)-4 alpha-Amino-2 alpha,3 beta-dihydroxy-1 alpha-cyclopentanemethanol (6), the carbocyclic analogue of xylofuranosylamine, was synthesized from the previously reported 4 alpha-acetamido-2 alpha,3 alpha-epoxycyclopentane-1 alpha-methanol. Amine 6 was converted to (+/-)-4 alpha-[(5-amino-6-chloro-4-pyrimidinyl)amino]-2 alpha,3 beta-dihydroxy-1 alpha-cyclopentanemethanol (7) by condensation with 5-amino-4,6-dichloropyrimidine. From 7, the carbocyclic analogues of xylofuranosyladenine and xylofuranosyl-8-azaadenine were prepared. In contrast to 9-beta-D-xylofuranosyladenine and its 8-aza analogue, the corresponding carbocyclic nucleosides were resistant to deamination by adenosine deaminase. The carbocyclic 8-aza derivative 10 exhibited significant in vivo antitumor activity which varied according to treatment schedule.
D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000633:toxicity; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D011684:Purine Nucleosides; D000243:Adenosine Deaminase