The taxane diterpenes comprise a group of plant-derived natural products possessing intriguing and important biological activity. In their interaction with the cytoskeleta and constituent proteins, several of the taxanes are unique among molecules acting on this cellular system and this mode of action further manifests itself in significant anti-leukemic and anti-tumor activity for several members of the group. In particular, taxol is now undergoing clinical trial for possible use as a chemotherapeutic agent against cancer. Low natural abundance of the taxanes, the desire to identify sub-structural elements responsible for their biological activity, the possibility that structurally modified taxanes might prove more advantageous therapeutically, and the organic chemical interest in their complex structures make these substances prime candidates for total synthesis research. The long range goal of the present research is to develop a general and flexible synthesis of the taxanes thereby providing synthetic access to natural substances of proven activity and to their structural analogues. Specifically, the initial objective will be to construct taxinine, a taxane possessing many structural features in common with the more complex and biologically active members. This work will model, in part, the eventual synthesis of taxol, representative of the most chemically and biologically intriguing taxanes. Finally, the preparation of enantiomerically pure taxanes, especially taxol, will be probed.
|Swindell, C S; Heerding, J M; Krauss, N E et al. (1994) Characterization of two taxol photoaffinity analogues bearing azide and benzophenone-related photoreactive substituents in the A-ring side chain. J Med Chem 37:1446-9|
|Rao, S; Krauss, N E; Heerding, J M et al. (1994) 3'-(p-azidobenzamido)taxol photolabels the N-terminal 31 amino acids of beta-tubulin. J Biol Chem 269:3132-4|
|Swindell, C S; Krauss, N E; Horwitz, S B et al. (1991) Biologically active taxol analogues with deleted A-ring side chain substituents and variable C-2' configurations. J Med Chem 34:1176-84|