Abstract
Taxinine is one of the member of the taxane diterpenoids which consist of an unique tricarbocyclic ring system with many asymmetric centers as well as oxygen functionalities. Using the cyclization method already accomplished by our group, the construction of the Taxinine carbon skeleton is achieved in a preferable endo fashion and with the desired stereochemistry at C-9, C-10 moiety similar to those of the natural product. The cyclized product 8 underwent several steps including stereoselective reduction of C-13 carbonyl group and oxidation of C-2 hydroxy group to give the aryl ketone 9. Birch reduction of 9 efficiently gave diol 10 which was then converted to the enone 12. The conjugate addition using organocopper reagent gave the product 13 with the desired stereochemistry of the 19 methyl group in excellent yield. Our next challenge to overcome was the stereoselective reduction of C-2 carbonyl group. This task was achieved by using Na metal in trifluoroethanol to give the desired 2α-alcohol 16 in a ratio of 10:1. Regioselective removal of the TBS group of alcohol 16 gave ketone 17, which is the most important intermediate in terms of having the required functionalities with the correct stereochemistry in rings A and B. Conversion of 17 into Taxinine is now under investigation.
