Synthesis and bioactivity of 2,4-diacyl analogues of paclitaxel

• Published in: Bioorganic & medicinal chemistry Vol. 9; no. 1; pp. 171 - 178
• Main Authors: Chordia, Mahendra D, Yuan, Haiqing, Jagtap, Prakash G, Kadow, John F, Long, Byron H, Fairchild, Craig R, Johnston, Kathy A, Kingston, David G.I
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2001; Elsevier Science
• Subjects: Antineoplastic agents; Antineoplastic Agents, Phytogenic - chemical synthesis; Biological and medical sciences; Cell Survival; General aspects; Humans; Medical sciences; Microtubule-Associated Proteins - biosynthesis; Molecular Structure; Paclitaxel - analogs & derivatives; Paclitaxel - chemical synthesis; Paclitaxel - pharmacology; Pharmacology. Drug treatments; Tumor Cells, Cultured - drug effects; Antineoplastic agent; Human; Terpenoid; Cytotoxicity; In vitro; Biological activity; Cell line; Analog; Multiple resistance; Taxane derivatives; Paclitaxel; Diterpene; Reversibility; Colon; Chemical synthesis; Acylation
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(00)00233-9

The 2,4-diacyl paclitaxel analogues 8a– 8r were prepared from paclitaxel by acylation of 4-deacetyl-2-debenzoylpaclitaxel 1,2-carbonate ( 3 ) followed either by hydrolysis of the carbonate and acylation or by direct treatment of the carbonate with an aryllithium. Some of the resulting derivatives showed significantly improved tubulin assembly activity and cytotoxicity as compared with paclitaxel; in some cases this improvement was especially significant for paclitaxel-resistant cell lines.