3,7-Dideazapurine nucleosides. Synthesis and antitumor activity of 1-deazatubercidin and 2-chloro-2'-deoxy-3,7-dideazaadenosine.
J Med Chem
; 32(7): 1463-6, 1989 Jul.
Article
en En
| MEDLINE
| ID: mdl-2641872
ABSTRACT
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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tubercidina
/
Antibacterianos
/
Antineoplásicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1989
Tipo del documento:
Article
País de afiliación:
Italia