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

K. Takao, J. Ishihara, K. Tadano

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

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
Title of host publicationStudies in Natural Products Chemistry
PublisherElsevier
Pages3-51
Number of pages49
EditionPART E
DOIs
Publication statusPublished - 2000

Publication series

NameStudies in Natural Products Chemistry
NumberPART E
Volume24
ISSN (Print)1572-5995

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry

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    Takao, K., Ishihara, J., & Tadano, K. (2000). Total syntheses of (+)-eremantholide a and (-)- verrucarol: From d-glucose to biologically intriguing sesquiterpenes. In Studies in Natural Products Chemistry (PART E ed., pp. 3-51). (Studies in Natural Products Chemistry; Vol. 24, No. PART E). Elsevier. https://doi.org/10.1016/S1572-5995(00)80043-5