Synthesis and antitumor activity of 2-beta-D-ribofuranosyloxazole-4-carboxamide (oxazofurin).
Condensation of 3,4,6-tri-O-benzoyl-2,5-anhydro-D-allonyl chloride (4) with ethyl 2-amino-2-cyanoacetate (5) provided 2-[(3',4',6'-tri-O-benzoyl-2',5'-anhydroallonyl)amino]-2-cyanoa cetate (6). Compound 6 was treated with hydrogen chloride gas to give ethyl 5-amino-2-(2',3',5'-tri-O-benzoyl-beta-D- ribofuranosyl)oxazole-4-carboxylate (8). Reductive dediazotization of blocked nucleoside 8 provided ethyl 2-(2',3',5'-tri-O- benzoyl-beta-D-ribofuranosyl)oxazole-4-carboxylate (10), which after deblocking with sodium methoxide and ammonolysis was converted to 2-beta-D-ribofuranosyl-oxazole-4-carboxamide (oxazofurin, 3), an analogue of the antitumor and antiviral C-nucleoside tiazofurin (1). Oxazofurin (3) was found to be cytotoxic toward B16 murine melanoma cells in culture but inactive against murine leukemia P388 and L1210.
Franchetti
P
P
Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
Cristalli
G
G
Grifantini
M
M
Cappellacci
L
L
Vittori
S
S
Nocentini
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D012254:Ribavirin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012266:Ribose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D010080:Oxazoles; C065915:oxazofurin; D012254:Ribavirin; D012266:Ribose; C033706:tiazofurin