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

Yoshikazu Suzuki, Kenichi Takao, Kin Ichi Tadano

Research output: Contribution to journalArticle

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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
Pages (from-to)127-167
Number of pages41
JournalStudies in Natural Products Chemistry
Volume29
Issue numberPART J
DOIs
Publication statusPublished - 2003

Fingerprint

Cycloaddition Reaction
Lactones
Carbon
RNA-Directed DNA Polymerase
Skeleton
Hot Temperature
Anti-Bacterial Agents
Stereoselectivity
Stereochemistry
Epoxidation
drimane
mniopetal E
Elongation
Derivatives
Molecules
kuehneromycin A
butenolide
arabitol
Human immunodeficiency virus 1 reverse transcriptase

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery

Cite this

Total synthesis of biologically intriguing drimane-type sesquiterpenoids via intramolecular diels-alder approaches. / Suzuki, Yoshikazu; Takao, Kenichi; Tadano, Kin Ichi.

In: Studies in Natural Products Chemistry, Vol. 29, No. PART J, 2003, p. 127-167.

Research output: Contribution to journalArticle

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