Total synthesis of merrilactone a: Long-range stereocontrol and asymmetric desymmetrization

Masayuki Inoue, Takaaki Sato, Masahiro Hirama

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

( - )-Merrilactone A [( - )-l], isolated from Illicium merrillianum in 2000, possesses neunte 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. Apart from its biological aspects, the caged pentacyclic skeleton of 1 poses interesting synthetic challenges. In this account, we describe the total synthesis of (+)- and ( - )-merrilactone A, based on two novel strategies. Both strategies employed, as a key step, a transannular aldol reaction of eight membered diketone to construct the core cis-bicyclo[3.3.0]octyl system of 1. In the first generation total synthesis, the 2,6bis(trifluoromethyl)benzyl group served as a long-range Stereocontrolling element for synthesis of the enantiopure bicyclo[3.3.0]octane framework of ( - )-l. On the other hand, asymmetric aldol reaction was developed in the second generation synthesis to build the fused core of (+)-l in a more consice manner. The obtained key intermediates were utilized as a platform for the subsequent functional group manipulations necessary for construction of ( - )- and (+)-l. Surprisingly, both the natural and unnatural enantiomers of 1 equally promoted neurite outgrowth in primary neuronal cultures.

Original languageEnglish
Pages (from-to)419-428
Number of pages10
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume65
Issue number5
Publication statusPublished - 2007 May 1
Externally publishedYes

Keywords

  • Asymmetric desymmetrization
  • Conformational analysis
  • Long-range stereocontrol
  • Merrilactone A
  • Meso compound
  • Neurotrophic factor
  • Pairwise symmetrical functionalization
  • Radical reaction
  • Sesquiterpenoid
  • Transannular aldol reaction

ASJC Scopus subject areas

  • Organic Chemistry

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