The research program described herein is directed toward the development of a general, asymmetric synthetic entry to the taxane diterpenes. This novel strategy features an anionic oxy-Cope rearrangement for the construction of a bicyclo[5.3.1]undecane suitably functionalized for eventual elaboration into taxinines E and J, baccatin I as well as the biologically more important taxanes taxol (NSC 12593) and cephalomannine. Both taxol and cephalomannine exhibit highly promising antitumor activity, and taxol is presently at the stage of clinical evaluation. The synthetic approah to this important class of molecules will be sufficiently flexible and efficient so that analogs may be readily prepared for a study of structure activity relationships. Selected compounds will be submitted to the National Cancer Institute for biological testing. As is the case in the synthesis of any complex molecule, it shall be necessary to invent new synthetic methods. Of particular importance for the present task will be the design and development of techniques for annelation of six-membered rings and stereoselective introduction of oxygen functionality. A study of the substituent effects in certain [3,3] sigmatropic rearrangements will be undertaken as will an examination of the efficacy of executing dienolate Diels-Alder reactions with a high degree of asymmetric induction.
| Lynch, V M; Fishpaugh, J R; Martin, S F et al. (1991) Structure of (+/-)-(1R*,6S*)-1-benzyloxy-8,11,11-trimethyl-6-phenylthiobicyclo [5.3.1 ]undec-7-en-3-one. Acta Crystallogr C 47 ( Pt 2):468-70 |
| Lynch, V M; Assercq, J M; Martin, S F et al. (1990) The structure of (4R*,7R*)-4,10,11,11-tetramethyl-5- oxobicyclo[5.3.1]undec-1(10)-en-4-carbaldehyde. Acta Crystallogr C 46 ( Pt 12):2472-4 |
