Synthesis of novel 3'-trifluoromethyl taxoids through effective kinetic resolution of racemic 4-CF3-beta-lactams with baccatins.
The coupling of racemic 1-tBoc-4-CF3-beta-lactams with various C-10 modified baccatins has resulted in CF3-taxoids with diastereoselectivities ranging from 9:1 to one single isomer. The observed high diastereoselectivity is ascribed to the highly efficient enantiomer-differentiation by the enantiopure lithium alkoxide of a baccatin III in the coupling reaction with a racemic 1-tBoc-beta-lactam. These novel CF3-taxoids have also been shown to exhibit significant increases in activity against various cancer cell lines compared to either paclitaxel or docetaxel. In addition, the first asymmetric synthesis of a CF3-beta-lactam via chiral ester enolate-imine cyclocondensation was performed with 50% enantioselectivity.
Ojima
I
I
Department of Chemistry, State University of New York at Stony Brook 11794-3400, USA.
Slater
J C
JC
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D047090:beta-Lactams
D000470:Alkaloids; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D047090:beta-Lactams; D017239:Paclitaxel