Total synthesis of biologically intriguing drimane-type sesquiterpenoids via intramolecular diels-alder approaches

Yoshikazu Suzuki, Ken Ichi Takao, Kin Ichi Tadano

研究成果: Chapter

4 被引用数 (Scopus)

抄録

The total syntheses of three drimane-type sesquiterpenoids, (-)-mnio-petal E, (-)-mniopetal F, and (-)-kuehneromycin A, are described. These na products innibit the enzymatic activity of RNA-directed DNA-polymerases (reverse transcriptases) of the human immunodeficiency virus (HIV)-1. Our enantiospeci total syntheses of these target molecules in naturally occurring forms commenced with a known 2,3-anhydro-D-arabinitol derivative, which was prepared using th Sharpless asymmetric epoxidation strategy. A combination of highly stereocontrolled inter- and intramolecular Horner-Emmons carbon elongations led to the tw butenolides tethering 1,2,4,9- and 1,4,9-functionalized nona-5,7-diene moieties at the β-carbon. The key step in mniopetal E synthesis is a stereoselective thermal intramolecular Diels-Alder reaction of the former butenolide compound, providing a highly oxygenated tricyclic skeleton with the desired endo an π-facial selections. The intramolecular Diels-Alder reaction of the latter butenolide compound for the syntheses of other two drimanes also proceeded with stereoselectivity, which is controlled by a balance of the steric effect and the stereoelectronic effect of a trialkylsilyloxy substituent existing adjacent t dienophile in accordance with Cieplak's theory. The transformation of the γ-lactone moiety in the cycloadducts to the γ-hydroxy-γ-lactone part was effic achieved via a tetracyclic intermediate. Our total syntheses of (-)-mniopetal E, (-)-mniopetal F, and (-)-kuehneromycin A established the unsettled absolute stereochemistries of the antibiotics. In addition, the reported total syntheses by Jauch are briefly reviewed.

本文言語English
ホスト出版物のタイトルStudies in Natural Products Chemistry
出版社Elsevier
ページ127-167
ページ数41
PART J
DOI
出版ステータスPublished - 2003

出版物シリーズ

名前Studies in Natural Products Chemistry
番号PART J
29
ISSN(印刷版)1572-5995

ASJC Scopus subject areas

  • 創薬
  • 有機化学

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