Synthesis and antitumor activity of 3'-deamino-3'-hydroxydoxorubicin. A facile procedure for the preparation of doxorubicin analogs.
Two successful routes have been developed for preparation of 3'-deamino-3'-hydroxydoxorubicin (11), based on protection of the 14-hydroxyl group of the aglycon by using tert-butylchlorodimethylsilane. The key intermediate, 14-O-tert-butyldimethylsilyl-7-O-(3,4-di-O-acetyl-2,6-dideoxy-alpha-L-ly xo -hexopyranosyl)adriamycinone (9), was successively deacetylated and desilylated in high yield to give the desired product 11. This route constitutes a general method of access to glycon-modified doxorubicin analogs. Compound 11 showed high antitumor activity in vivo in the murine P388 lymphocytic leukemia assay.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D015251:Epirubicin / Q000031:analogs & derivatives*; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice
D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; C042907:3'-deamino-3'-hydroxydoxorubicin; D004317:Doxorubicin