(—)-Isochaetominine推测结构的对映选择性全合成与结构修正

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

报道生物碱isochaetominine推测结构8的对映选择性全合成与结构修正.采用立体多样性合成策略,通过L-色氨酸与L-丙氨酸苄酯组合,以DMDO氧化启动的串联反应为关键反应,经5步高效地完成了isochaetominine推测结构8及其立体异构体(+)-2,3,14-tri-epi-chaetominine(12)的全合成.基于本实验室此前有关毛壳菌素(1)立体多样性合成的工作,天然isochaetominine的结构修正为(-)-11-epi-chaetominine(18).我们此前已完成了该天然产物的首次对映选择性全合成(从L-色氨酸出发,5步,总产率31.6%).此外,通过研究色氨酸与缬氨酸叔丁酯组合,建立了isochaetominine C三个非对映立体异构体的立体多样性合成.最后,证实了化合物13B无法进行C(14)位定点差向异构化,但可以进行C(11)和C(14)双差向异构化.

In this paper, the enantioselective total synthesis and structure revision of the proposed structure of isochaetominine 8 are described. On the basis of the stereodivergent strategy, a highly efficient five-step synthesis of the proposed structure 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 reaction as a key step. A comparison of the physical and spectral data of the natural isochaetominine with those of the diastereomers obtained during our previous stereodivergent synthesis of chaetominine（1）, allowed revising the structure of isochaetominine as（-）-11-epi-chaetominine（18）. The first enantioselective total synthesis of this natural product has been accomplished 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 13 B led to a bis-epimerization at both C（14） and C（11）.