3,7-Dideazapurine nucleosides. Synthesis and antitumor activity of 1-deazatubercidin and 2-chloro-2'-deoxy-3,7-dideazaadenosine.
1-Deazatubercidin (5) has been synthesized by glycosylation of the anion of 4,6-dichloro-1H-pyrrolo[3,2-c]pyridine (9) with 1-chloro-2,3-O-isopropylidene-5-O-(tert-butyldimethylsilyl)-alpha-D-r ibofuranos e (12). The reaction gave a mixture of blocked nucleosides with beta- and alpha-configuration (13a and 13b). Deprotection of 13a provided 4,6-dichloro-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (14), which on treatment with hydrazine, followed by reduction of the resulting 4-hydrazino compound with Raney nickel, gave 4-amino-6-chloro-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (15), 1-deazatubercidin, and a small quantity of 4,6-diamino-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (16). Dehalogenation of 15 provided another route to 5. 2-Chloro-2'-deoxy-3,7-dideazaadenosine (6) together with 2'-deoxy-3,7-dideazaadenosine (18) was obtained by hydrazinolysis of 4,6-dichloro-1-(2-deoxy-beta-D-erythro-pentofuranosyl)pyrrolo- [3,2-c]pyridine (17), followed by reduction of the resulting 4-hydrazino compound. Nucleosides 5, 6, 15, and 18 are devoid of any significant antitumor activity in vitro. Compound 16 showed significant activity against P388 leukemia in cell culture.
Cristalli
G
G
Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
Franchetti
P
P
Grifantini
M
M
Nocentini
G
G
Vittori
S
S
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D007939:Leukemia L1210 / Q000473:pathology; D007941:Leukemia P388 / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D051379:Mice; D014372:Tubercidin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; C060145:2-chloro-2'-deoxy-3,7-dideazaadenosine; C036159:1-deazatubercidin; D014372:Tubercidin