Synthesis of docetaxel and butitaxel analogues through kinetic resolution of racemic beta-lactams with 7-O-triethylsilylbaccatin III.
The kinetic resolution of racemic cis-4-phenyl- and cis-4-tert-butyl-3-hydroxy-beta-lactam derivatives with 7-O-triethylsilylbaccatin III yielded paclitaxel and butitaxel analogues with high diastereoselectivity. The results demonstrated that the tert-butyldimethylsilyl protecting group at the C3-hydroxy group of the beta-lactams provided optimum kinetic resolution in comparison with the sterically less demanding triethylsilyl group and the larger triisopropylsilyl group. In addition, it was found that the C4 beta-lactam substituents also influenced diastereoselectivity. The C4 tert-butyl-beta-lactams provided better diastereoselectivity than the corresponding C4 phenyl beta-lactams.
Ge
Haibo
H
Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Drive, University of Kansas, Lawrence, Kansas 66045-7582, USA.
Spletstoser
Jared T
JT
Yang
Yan
Y
Kayser
Margaret
M
Georg
Gunda I
GI
D000470:Alkaloids / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D000077143:Docetaxel; D007700:Kinetics; D008956:Models, Chemical; D013237:Stereoisomerism; D043823:Taxoids / Q000138:chemical synthesis* / Q000737:chemistry*; D047090:beta-Lactams / Q000737:chemistry*
D000470:Alkaloids; D000970:Antineoplastic Agents; D043823:Taxoids; D047090:beta-Lactams; C103910:butitaxel; D000077143:Docetaxel; C073950:baccatin III