Design and synthesis of simplified taxol analogs based on the T-Taxol bioactive conformation

作者：Zhao Jielu; Bane Susan; Snyder James P; Hu Haipeng; Mukherjee Kamalika; Slebodnick Carla; Kingston David G I^*

来源：Bioorganic & Medicinal Chemistry, 2011, 19(24): 7664-7678.

DOI：10.1016/j.bmc.2011.10.010

• Simplified paclitaxel
• T-Taxol
• Bioactive conformation
• Taxol
• Paclitaxel
• X-ray
• Modeling
• Tubulin
• Antiproliferative activity

A series of compounds designed to adopt a conformation similar to the tubulin-binding T-Taxol conformation of the anticancer drug paclitaxel has been synthesized. Both the internally bridged analogs 37-39, 41 and the open- chain analogs 27-29 and 43 were prepared. The bridged analogs 37-39 and 41 were synthesized by Grubbs' metatheses of compounds 30-32 and 33, which, in turn, were prepared by coupling beta-lactams 24-26 with alcohols 22 and 23. Both the bridged and the open- chain analogs showed moderate to good cytotoxicity.

• 出版日期2011-12-15
• 单位美国弗吉尼亚理工大学(Virginia Tech)