Total Synthesis of (±)-Nominine, a Heptacyclic Hetisine-Type Aconite Alkaloid

• Muratake Hideaki

  Research Foundation Itsuu Laboratory

• Natsume Mitsutaka

  Research Foundation Itsuu Laboratory

Bibliographic Information

Other Title

• 7環性アコニットアルカロイド(±)-Nominineの全合成

Abstract

The palladium-catalyzed intramolecular α-arylation of formyl group was successfully applied to a total synthesis of (±)-nominine, a heptacyclic hetisine-type aconite alkaloid isolated from Aconitum sanyoense Nakai in 1956. The synthesis consists of forty-steps from 2-bromo-5-methoxyphenethyl iodide, and constitutes the first total synthesis of a hetisine-type aconite alkaloid, the sole representative aconite skeleton whose total synthesis has remained unsuccessful. Key steps other than the above α-arylation are (i) acetal ene-reaction to form the C14–C20 bond, (ii) LiAlH₄ reduction of cyano-enol silyl ether to form the N–C6 bond, (iii) radical cyclization from enyne precursor to construct the methylenebicyclo[2.2.2]octane framework, and (iv) allylic oxidation with SeO₂–tert-BuOOH to introduce 15β-OH. Completion of the synthesis was verified unequivocally by single crystal X-ray analysis of (±)-nominine.

Journal

• Proceedings of the Symposium on Progress in Organic Reactions and Syntheses

  Proceedings of the Symposium on Progress in Organic Reactions and Syntheses 30 (0), 288-289, 2004

  Division of Organic Chemistry, The Pharmaceutical Society of Japan

Keywords

• nominine
• aconite alkaloid
• heptacycle
• hetisine
• total synthesis

Details

• CRID: 1390001205634987648
• NII Article ID: 130006997461
• DOI: 10.14895/hannou.30.0.288.0
• Data Source:
  • JaLC
  • CiNii Articles
• Abstract License Flag: Disallowed