Structure-activity relationships of taxol®: synthesis and biological evaluation of C2 taxol analogs

✍ Scribed by Shu-Hui Chen; Vittorio Farina; Jian-Mei Wei; Bryon Long; Craig Fairchild; Stephen W. Mamber; John F. Kadow; Dolatrai Vyas; Terrence W. Doyle

• Publisher: Elsevier Science
• Year: 1994
• Tongue: English
• Weight: 278 KB
• Volume: 4
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/0960-894x(94)80020-0

✦ Synopsis

Red-Al was used to selectively remove the C2 benroate of 7,13-bisTES baccatin (8). Derivatization of the resulting Cz hydroxy compound provided the corresponding p-nitrophenyl ~arbamate, the p-methoxy and p-nitrobenzoates, and cyclohexyl ester. Attachment of the tax01 side chain to the above four analogs via lactam (IS) followed by desilylation provided five analogs of taxol modified at the Cz position, including a Cl2 cyclic carbonate. These five analogs were less potent than taxol in a tubulin polymerization assay and a cytotoxicity assay against human colon cancer cell line.