Enantiocontrolled total synthesis of (-)-mersicarpine

Yusuke Iwama, Kentaro Okano, Kenji Sugimoto, Hidetoshi Tokuyama

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

A racemic synthesis of mersicarpine (1) was achieved by the Mizoroki-Heck reaction and a DIBALH-mediated reductive ring-expansion reaction. Based on a first-generation synthesis, a second-generation enantiocontrolled total synthesis of (-)-mersicarpine (1) was achieved by an 8-pot/11-step sequence in 21 % overall yield from commercially available 2-ethylcyclohexanone. Subjection of a ketoester, which was prepared by an asymmetric Michael addition (according to the protocol by d'Angelo and Desmaële), and phenylhydrazine to modified Fischer indole conditions provided a six-membered tricyclic indole. Benzylic oxidation and subsequent oxime formation provided a ketoxime, which was treated with diisobutylaluminum hydride (DIBALH) to construct the characteristic azepinoindole skeleton in good yield. In the DIBALH-mediated reductive ring-expansion reaction, gradually increasing the reaction temperature and in situ-protection of the nitrogen in an oxygen-sensitive azepinoindole with a benzyloxycarbonyl (Cbz) group were crucial for the high-yielding process. With these methodologies, the short-step and efficient synthesis of (-)-mersicarpine was accomplished. Several synthetic efforts are also described.

Original languageEnglish
Pages (from-to)9325-9334
Number of pages10
JournalChemistry - A European Journal
Volume19
Issue number28
DOIs
Publication statusPublished - 2013 Jul 8

Keywords

  • mersicarpine
  • natural products
  • ring expansion
  • synthetic methods
  • total synthesis

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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