Total Synthesis of Merrilactone A: Long-Range Stereocontrol and Asymmetric Desymmetrization

• Inoue Masayuki

  Graduate School of Pharmaceutical Sciences, The University of Tokyo

• Sato Takaaki

  カリフォルニア大学アーバイン校

• Hirama Masahiro

  東北大学大学院理学研究科

Bibliographic Information

Other Title

• メリラクトンＡの全合成：遠隔不斉誘導と不斉非対称化
• メリラクトン A ノ ゼンゴウセイ エンカク フセイ ユウドウ ト フセイ ヒタイショウカ
• Long-Range Stereocontrol and Asymmetric esymmetrization
• 遠隔不斉誘導と不斉非対称化

Abstract

(-)-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. 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, 6-bis (trifluoromethyl) benzyl group served as a long-range stereocontrolling element for synthesis of the enantiopure bicyclo [3.3.0] octane frame-work of (-)-1. On the other hand, asymmetric aldol reaction was developed in the second generation synthesis to build the fused core of (+)-1 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 (+)-1. Surprisingly, both the natural and unnatural enantiomers of 1 equally promoted neurite outgrowth in primary neuronal cultures.

Journal

• Journal of Synthetic Organic Chemistry, Japan

  Journal of Synthetic Organic Chemistry, Japan 65 (5), 419-429, 2007

  The Society of Synthetic Organic Chemistry, Japan

Keywords

• merrilactone A
• sesquiterpenoid
• neurotrophic factor
• conformational analysis
• meso compound
• pairwise symmetrical functionalization
• transannular aldol reaction
• radical reaction
• long-range stereocontrol
• asymmetric desymmetrization

Details

• CRID: 1390282680289308288
• NII Article ID: 10020137613
• NII Book ID: AN0024521X
• DOI: 10.5059/yukigoseikyokaishi.65.419
• ISSN: 18836526
• ISSN: 00379980
• NDL BIB ID: 8817759
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I8817759
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed