Chemical modification of an antitumor alkaloid, 20(S)-camptothecin: glycosides, phosphates and sulfates of 7-ethyl-10-hydroxycamptothecin.
Water-soluble derivatives having the lactone ring intact were synthesized starting from 7-ethyl-10-hydroxycamptothecin (1). Glycosides (2) of the phenolic hydroxyl group of 1 were obtained by reaction with acetylated alpha-bromosugars in acetone or aqueous acetone in the presence of potassium carbonate, followed by deprotection. Phosphates (3) were prepared by reaction of 1 with phosphoryl chloride in pyridine or with dibenzylchlorophosphoridate. Sulfates (4) were obtained by reaction of 1 with sulfur trioxide-pyridine complex in the presence of a tertiary amine. The organic ammonium salts of monophosphate (3p) and sulfates (4a and 4b) showed significant activity against L1210 in vivo.
Yaegashi
T
T
Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Nokata
K
K
Sawada
S
S
Furuta
T
T
Yokokura
T
T
Miyasaka
T
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D006027:Glycosides / Q000138:chemical synthesis / Q000494:pharmacology; D000077146:Irinotecan; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D010710:Phosphates / Q000138:chemical synthesis / Q000494:pharmacology; D013431:Sulfates / Q000138:chemical synthesis / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D006027:Glycosides; D010710:Phosphates; D013431:Sulfates; D000077146:Irinotecan; D002166:Camptothecin