An approach to the total synthesis of aplysiatoxin

Robert E. Ireland, Suvit Thaisrivongs, Patrick H. Dussault

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

An approach to the synthesis of the polyacetate tumor promoter aplysiatoxin is described. The spiroketal framework was convergently constructed in a heteroatom Diels-Alder reaction between an enol ether and a vinyl ketone. The desired spirocenter stereochemistry was obtained by acid-catalyzed isomerization to the less sterically encumbered spiroketal. Subsequent manipulation provided diastereomeric 9-hydroxy derivatives (aplysiatoxin numbering) epimeric at C-15. These spiroketal alcohols were envisaged as key intermediates for attempted introduction of the C-3 lactol, as well as for appendage of the 12-membered bis(lactone). Attempted transannular remote oxidation using the derived C-9 alkoxy radical failed, however, to introduce the lactol. The 9-hydroxy derivatives were efficiently converted into bis(acetones), utilizing the photodeprotection of a nitrobenzyl ether as a key step. Bromination and deprotection afforded both possible C-15 epimers of 3-desoxyaplysiatoxin-20-O methyl ether. Circular dichroism spectra of synthetic intermediates provided a means of distinguishing the diastereomer with the natural C-15 stereochemistry. Nuclear Overhauser effect difference spectra on the bis(lactones) showed signal enhancement within the rigid spiroketal framework consistent with those reported for derivatives of the natural product.

Original languageEnglish (US)
Pages (from-to)5768-5779
Number of pages12
JournalJournal of the American Chemical Society
Volume110
Issue number17
DOIs
StatePublished - Aug 1988

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Ethers
Stereochemistry
Derivatives
Lactones
Ether
Dichroism
Isomerization
Ketones
Methyl Ethers
Acetone
Tumors
Halogenation
Cycloaddition Reaction
Alcohols
Circular Dichroism
Biological Products
Carcinogens
Oxidation
Acids
aplysiatoxin

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

An approach to the total synthesis of aplysiatoxin. / Ireland, Robert E.; Thaisrivongs, Suvit; Dussault, Patrick H.

In: Journal of the American Chemical Society, Vol. 110, No. 17, 08.1988, p. 5768-5779.

Research output: Contribution to journalArticle

Ireland, Robert E. ; Thaisrivongs, Suvit ; Dussault, Patrick H. / An approach to the total synthesis of aplysiatoxin. In: Journal of the American Chemical Society. 1988 ; Vol. 110, No. 17. pp. 5768-5779.
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