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

Yoshikazu Suzuki, Ken Ichi Takao, Kin Ichi Tadano

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Title of host publicationStudies in Natural Products Chemistry
PublisherElsevier
Pages127-167
Number of pages41
EditionPART J
DOIs
Publication statusPublished - 2003

Publication series

NameStudies in Natural Products Chemistry
NumberPART J
Volume29
ISSN (Print)1572-5995

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry

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    Suzuki, Y., Takao, K. I., & Tadano, K. I. (2003). Total synthesis of biologically intriguing drimane-type sesquiterpenoids via intramolecular diels-alder approaches. In Studies in Natural Products Chemistry (PART J ed., pp. 127-167). (Studies in Natural Products Chemistry; Vol. 29, No. PART J). Elsevier. https://doi.org/10.1016/S1572-5995(03)80006-6