Total synthesis of polycavernoside A, a lethal toxin of the red alga Polycavernosa tsudai

Paul R. Blakemore, Cindy C Browder, Jian Hong, Christopher M. Lincoln, Pavel A. Nagornyy, Lonnie A. Robarge, Duncan J. Wardrop, James D. White

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Two approaches to the synthesis of the aglycon 120 of polycavernoside A (1) were developed, only one of which was completed. The successful "second-generation" route assembled the aglycon seco acids 102 and 106 via Nozaki-Hiyama-Kishi coupling of aldehyde 70, prepared from methyl (S)-3-hydroxy-2-methylpropionate (72) and (S)-pantolactone (73), with vinyl bromide 71. The latter was obtained from a sequence which commenced from the silyl ether 24 of 3-hydroxypropionaldehyde and entailed cyclization of (Z)-ζ-hydroxy-α,β-unsaturated ester 82. Regioselective Yamaguchi lactonization of trihydroxycarboxylic acids 102 and 106 and subsequent functional-group adjustments led to macrolactone 120, to which the fucopyranosylxylopyranoside moiety was attached. Stille coupling of the glycosidated aglycon 128 with dienylstannane 129 furnished polycavernoside A in a synthesis for which the longest linear sequence was 25 steps. The overall yield to lactone 120 was 4.7%.

Original languageEnglish (US)
Pages (from-to)5449-5460
Number of pages12
JournalJournal of Organic Chemistry
Volume70
Issue number14
DOIs
StatePublished - Jul 8 2005
Externally publishedYes

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Algae
Acids
Cyclization
Lactones
Aldehydes
Ether
Functional groups
Esters
polycavernoside A
3-hydroxypropionaldehyde
vinyl bromide
pantolactone

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Blakemore, P. R., Browder, C. C., Hong, J., Lincoln, C. M., Nagornyy, P. A., Robarge, L. A., ... White, J. D. (2005). Total synthesis of polycavernoside A, a lethal toxin of the red alga Polycavernosa tsudai. Journal of Organic Chemistry, 70(14), 5449-5460. https://doi.org/10.1021/jo0503862

Total synthesis of polycavernoside A, a lethal toxin of the red alga Polycavernosa tsudai. / Blakemore, Paul R.; Browder, Cindy C; Hong, Jian; Lincoln, Christopher M.; Nagornyy, Pavel A.; Robarge, Lonnie A.; Wardrop, Duncan J.; White, James D.

In: Journal of Organic Chemistry, Vol. 70, No. 14, 08.07.2005, p. 5449-5460.

Research output: Contribution to journalArticle

Blakemore, PR, Browder, CC, Hong, J, Lincoln, CM, Nagornyy, PA, Robarge, LA, Wardrop, DJ & White, JD 2005, 'Total synthesis of polycavernoside A, a lethal toxin of the red alga Polycavernosa tsudai', Journal of Organic Chemistry, vol. 70, no. 14, pp. 5449-5460. https://doi.org/10.1021/jo0503862
Blakemore, Paul R. ; Browder, Cindy C ; Hong, Jian ; Lincoln, Christopher M. ; Nagornyy, Pavel A. ; Robarge, Lonnie A. ; Wardrop, Duncan J. ; White, James D. / Total synthesis of polycavernoside A, a lethal toxin of the red alga Polycavernosa tsudai. In: Journal of Organic Chemistry. 2005 ; Vol. 70, No. 14. pp. 5449-5460.
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