title: Nucleic acid related compounds. 51. Synthesis and biological properties of sugar-modified analogues of the nucleoside antibiotics tubercidin, toyocamycin, sangivamycin, and formycin.
abstract: Treatment of 7-amino-3-beta-D-ribofuranosylpyrazolo[4,3-d]pyrimidine (formycin) with alpha-acetoxyisobutyryl bromide followed by deprotection of the resulting trans-vicinal acetoxy bromides and hydrogenolysis of the separated bromohydrins gave 2'-deoxy-(23%) and 3'-deoxyformycin (32%) after complete deprotection and purification of their hydrochloride salts. An analogous sequence gave 3'-deoxytoyocamycin and/or 3'-deoxysangivamycin in approximately 80% yields from toyocamycin. Antiviral, antineoplastic, and antimetabolic effects were evaluated for the formycin compounds and 4-amino-7-beta-D-ribofuranosylpyrrolo[2,3-d]pyrimidine (tubercidin), its 5-cyano- (toyocamycin), and 5-carbamoyl-(sangivamycin) antibiotic congeners in comparison with their 2'-deoxy, 3'-deoxy, and arabino analogues. In all cases, the modified-sugar compounds were less cytotoxic than the parent antibiotics. The majority also exhibited lower antiviral potency. However, the xylo-tubercidin analogue retained potent antiherpes 1 and 2 activity with decreased cytotoxicity. Labeled metabolite studies suggested that effects of these compounds on RNA and/or protein synthesis might be more significant than interference with DNA synthesis.
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D000998:Antiviral Agents / Q000138:chemical synthesis*; D005573:Formycins / Q000138:chemical synthesis* / Q000494:pharmacology; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D008826:Microbial Sensitivity Tests; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000494:pharmacology; D012263:Ribonucleosides / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D014127:Toyocamycin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D014372:Tubercidin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D000998:Antiviral Agents; D005573:Formycins; D011741:Pyrimidine Nucleosides; D012263:Ribonucleosides; C005699:sangivamycin; D014127:Toyocamycin; D014372:Tubercidin