Enantioselective Total Synthesis and Structural Revision of (－)-Isochaetominine

Abstract

In this paper, the enantioselective total synthesis and structure revision of the proposed structure of isochaetom- inine 8 are described. On the basis of the stereodivergent strategy, a highly efficient five-step synthesis of the proposed struc- ture of isochaetominine 8 and its diastereomer (+)-2,3,14-tri-epi-chaetominine (12) was achieved. The method features the use of L-tryptophan and L-alanine benzyl ester as the starting materials, and a dimethyldioxirane (DMDO)-triggered tandem reac- tion as a key step. A comparison of the physical and spectral data of the natural isochaetominine with those of the diastere- omers obtained during our previous stereodivergent synthesis of chaetominine (1), allowed revising the structure of isochae- tominine as (-)-11-epi-chaetominine (18). The first enantioselective total synthesis of this natural product has been accom- plished previously in our laboratories in five steps, 31.6% overall yield from L-tryptophan. Besides, an investigation on the L-tryptophan and L-valine tert-butyl ester-based synthesis of isochaetominine C resulted in a stereodivergent synthesis of three diastereomers of isochaetominine C. Finally, it was revealed that attempted site selective epimerization at C(14) of 13B led to a bis-epimerization at both C(14) and C(11). Keywords alkaloids; isochaetominine; total synthesis; structural revision; stereodivergent synthesis; epimerization