Pyrrolopyrimidine nucleosides. 18. Synthesis and chemotherapeutic activity of 4-amino-7-(3-deoxy-beta-D-ribofuranosyl)pyrrolo[2,3-d] pyrimidine-5-carboxamide (3'-deoxysangivamycin) and 4-amino-7-(2-deoxy-beta-D-ribofuranosyl)pyrrolo[2,3-d] pyrimidine-5-carboxamide (2'-deoxysangivamycin).
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| Abstract |
A multistep synthesis, using the nucleoside antibiotic toyocamycin as the starting material, has furnished 6,2'-S-cyclosangivamycin (6). Desulfurization of 6,2'-S-cyclosangivamycin (6) with Raney nickel has provided 2'-deoxysangivamycin (7). Treatment of sangivamycin (1c) with sodium iodide and alpha-acetoxyisobutyryl chloride has furnished 4-amino-7-[2-O-acetyl-3-deoxy-3-iodo-5-O-(2,5,5-trimethyl-4-oxo-1, 3-dioxolan-2-yl)-beta-D-xylofuranosyl]-pyrrolo[2,3-d] pyrimidine-5-carboxamide (8a). Dehalogenation of 8a with 10% palladium on charcoal was followed by a removal of the blocking groups with ammonium hydroxide to give 3'-deoxysangivamycin (9) in 49% overall yield. The reaction of sangivamycin (1c) with diphenyl disulfide and tributylphosphine gave 5'-(phenylthio)-5'-deoxysangivamycin (10). Treatment of 10 with Raney Nickel afforded 5'-deoxysangivamycin (11). Antitumor evaluation showed that 3'-deoxysangivamycin had significant activity against the murine leukemia L1210 both in vivo and in vitro, although it was less potent on a molar basis than the parent compound sangivamycin. The 2'- and 5'-deoxysangivamycins did not show significant antitumor activity.
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| Authors | T Maruyama, L L Wotring, L B Townsend |
| Journal | Journal of medicinal chemistry (J Med Chem) Vol. 26 Issue 1 Pg. 25-9 (Jan 1983) ISSN: 0022-2623 [Print] United States |
| PMID | 6827526 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
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