Rakumitsu Kenta, Sakamoto Jukiya, Ishikawa Hayato
Department of Chemistry, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto, 860-8555, Japan.
Faculty of Advanced Science and Technology, Kumamoto University, 2-39-1, Kurokami, Chuo-ku, Kumamoto, 860-8555, Japan.
Chemistry. 2019 Jul 5;25(38):8996-9000. doi: 10.1002/chem.201902073. Epub 2019 Jun 6.
The first enantioselective total syntheses of (-)-secologanin (1), (-)-5-carboxystrictosidine (2), and (-)-rubenine (3) were accomplished in 10, 9, and 14 steps, respectively. The key transformation in the synthesis of 1 was a sequential anti-selective organocatalytic Michael reaction/Fukuyama reduction/spontaneous cyclization to form an optically active dihydropyran ring. In addition, the secologanin tetraacetate (16), which is a potential key intermediate for the bioinspired divergent syntheses of monoterpenoid indole alkaloids, was prepared in gram-scale in seven steps. The total syntheses of 2 and 3, which are classified as glycosylated monoterpenoid indole alkaloids, were achieved through bioinspired transformations such as a diastereoselective Pictet-Spengler reaction, a site- and stereoselective epoxidation, and a site-selective epoxide ring-opening followed by a lactonization reaction.
分别以10步、9步和14步完成了（-）-裂环番木鳖苷（1）、（-）-5-羧基 strictosidine（2）和（-）-鲁贝宁（3）的首次对映选择性全合成。合成1的关键转化是依次进行反选择性有机催化迈克尔反应/福山还原/自发环化，以形成光学活性的二氢吡喃环。此外，以七步克级规模制备了裂环番木鳖苷四乙酸酯（16），它是用于单萜吲哚生物碱仿生发散合成的潜在关键中间体。2和3属于糖基化单萜吲哚生物碱，通过诸如非对映选择性 Pictet-Spengler反应、位点和立体选择性环氧化以及位点选择性环氧开环随后内酯化反应等仿生转化实现了它们的全合成。
