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

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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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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., Wardrop, D. J., & 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