Total synthesis of hypermodified epothilone analogs with potent in vitro antitumor activity.
The convergent total synthesis of hypermodified epothilone analogs 1 and 2 has been achieved with the stereoselective cyclopropanation of allylic alcohol 17 and ring-closing olefin metathesis with diene 22 as the key steps. In spite of significant structural differences between these analogs and the natural epothilone scaffold, 1 and 2 are potent inducers of tubulin polymerization and inhibit the growth of human cancer cells in vitro with sub-nM IC50 values.
Kuzniewski
Christian N
CN
Swiss Federal Institute of Technology (ETH) Zürich, HCI H405, Wolfgang-Pauli-Str. 10, CH-8093 Zürich, Switzerland.
Gertsch
Jürg
J
Wartmann
Markus
M
Altmann
Karl-Heinz
KH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D034261:Epothilones / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure
D000970:Antineoplastic Agents; D034261:Epothilones