Synthesis of Docetaxel and Butitaxel Analogues through Kinetic Resolution of Racemic β-Lactams with 7- O -Triethylsilylbaccatin III

Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas, United States
The Journal of Organic Chemistry (Impact Factor: 4.72). 03/2007; 72(3):756-9. DOI: 10.1021/jo061339s
Source: PubMed


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.

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