Total syntheses of (+)-eremantholide a and (-)- verrucarol: From d-glucose to biologically intriguing sesquiterpenes

Kenichi Takao, J. Ishihara, K. Tadano

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Abstract

The total syntheses of two sesquiterpenes, (+)-eremantholide A and (-)-verrucarol, are described. Both syntheses commenced with our previously introduced enantiomerically pure building block, (2R,3R,4R,5S)-4-(ethoxycarbonyl)methyl-2,3- (isopropylidenedioxy)-5-[(1R)-1,2- (isopropylidenedioxy)ethyl]-4-vinyltetrahydrofuran. This starting material was readily prepared from D-glucose in a five-step reaction, featuring a highly stereoselective orthoester Claisen rearrangement. The total synthesis of (+)-eremantholide A was characterized by (1) a regio- and stereoselective radical carbocyclization as a clue to the B-ring construction, (2) coupling reaction of the A/B ring equivalent with 5-ethyl-2-methyl-3(2H)- furanone, and (3) the final nine-membered ring closure by a vinylogous aldol reaction. The key steps for the totalsynthesis of (-)-verrucarol were (1) an intramolecular Knoevenagel cyclization for construction of the A-ring precursor, (2) sequential carbon-carbon bond formations for introduction of the quaternary stereogenic carbon sharing the B- and C-rings, (3) a Dieckmann cyclization for construction of the C-ring equivalent, (4) a skeletal enlargement strategy for the entire trichothecene skeleton construction, and (5) the finalstereoselective epoxidation at the methylene carbon in the bridge constituting the B- and C-rings. In addition, the reported synthetic efforts devoted to eremantholide A and verrucarol are briefly reviewed.

Original languageEnglish
Pages (from-to)3-51
Number of pages49
JournalStudies in Natural Products Chemistry
Volume24
Issue numberPART E
DOIs
Publication statusPublished - 2000

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Sesquiterpenes
Carbon
Glucose
Cyclization
Trichothecenes
Epoxidation
Skeleton
verrucarol
eremantholide
eremantholide A

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery

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Total syntheses of (+)-eremantholide a and (-)- verrucarol : From d-glucose to biologically intriguing sesquiterpenes. / Takao, Kenichi; Ishihara, J.; Tadano, K.

In: Studies in Natural Products Chemistry, Vol. 24, No. PART E, 2000, p. 3-51.

Research output: Contribution to journalArticle

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