Total synthesis and bioactivity of an unnatural enantiomer of merrilactone A: Development of an enantioselective desymmetrization strategy

Masayuki Inoue, Nayoung Lee, Satoshi Kasuya, Takaaki Sato, Masahiro Hirama, Miyako Moriyama, Yoshiyasu Fukuyama

研究成果: Article査読

70 被引用数 (Scopus)

抄録

(Chemical Equation Presented) (-)-Merrilactone A [(-)-1], isolated from Illicium merrillianum in 2000, possesses neurite outgrowth activity in cultures of fetal rat cortical neurons, and, therefore, is expected to show therapeutic potential for the treatment of neurodegeneration associated with Alzheimer's and Parkinson's diseases. A part from its biological aspects, the caged pentacyclic skeleton of 1 poses interesting synthetic challenges. Here, we report the total synthesis of the unnatural enantiomer of merrilactone A [(+)-1], based on a novel desymmetrization strategy. The chiral lithium amide 16g promoted an enantioselective transannular aldol reaction of eight-membered meso-diketone 3d, establishing the absolute stereochemistries of four chiral centers of the cis-bicyclo[3.3.0]octane framework of 1 in a single step. The obtained compound 4d served as a platform for the subsequent functional group manipulations necessary for the construction of (+)-1. Surprisingly, both the natural and unnatural enantiomers of synthetic merrilactone A equally promoted neurite outgrowth in primary neuronal cultures.

本文言語English
ページ(範囲)3065-3075
ページ数11
ジャーナルJournal of Organic Chemistry
72
8
DOI
出版ステータスPublished - 2007 4月 13
外部発表はい

ASJC Scopus subject areas

  • 有機化学

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