Synthesis and anti-tubulin activity of a 3'-(4-azidophenyl)-3'-dephenylpaclitaxel photoaffinity probe.
The synthesis and biological evaluation of a novel paclitaxel photoaffinity probe is described. The synthesis involved the preparation of an azide-containing C13 side chain through a Staudinger cycloaddition followed by a lipase-mediated kinetic resolution to obtain the azetidinone in 99% ee. Coupling of the enantiopure side chain precursor to 7-TES-baccatin III and subsequent silyl ether deprotection afforded 3'-(4-azidophenyl)-3'-dephenylpaclitaxel, which was shown to be as active as paclitaxel in tubulin assembly and cytotoxicity assays.
Spletstoser
Jared T
JT
Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045-7582, USA.
Flaherty
Patrick T
PT
Himes
Richard H
RH
Georg
Gunda I
GI
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001386:Azides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D003500:Cyclization; D015394:Molecular Structure; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D019920:Photoaffinity Labels / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators
C495226:3'-(4-azidophenyl)-3'-dephenylpaclitaxel; D000970:Antineoplastic Agents; D001386:Azides; D019920:Photoaffinity Labels; D014404:Tubulin; D050257:Tubulin Modulators; D017239:Paclitaxel