A highly efficient kinetic resolution of racemic cis-4-(2-tert-butyldimethylsilyloxy-1,1-dimethyl)ethyl-3-tert-butyldimethylsilyloxy-azetidin-2-one with 7-O-triethylsilylbaccatin III was carried out to furnish 10-O-acetyl-5′-hydroxybutitaxel after removal of the silyl protecting groups. The compound was 50% as active as paclitaxel in a tubulin assembly assay and showed significantly decreased activity against MCF7 cell proliferation compared to paclitaxel.
Bibliographical noteFunding Information:
The authors wish to thank the National Cancer Institute for financial support of this research (NIH CA82801 and NIH CA105305), NBIF Research Assistantship Initiative, and Tapestry Pharmaceuticals (Boulder, CO) for a generous gift of 10-deacetylbaccatin III. We wish to thank Christopher Schneider for his help with the HPLC analysis. We also thank Jacquelyn K. Huff for her excellent technical assistance.
- Kinetic resolution
- NCI/ADR RES
- Paclitaxel analogues
- Tubulin assembly