Total synthesis of the spirocyclic imine marine toxin (-)-gymnodimine and an unnatural C4-epimer

Ke Kong, Ziad Moussa, Changsuk Lee, Daniel Romo

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

The first total synthesis of the marine toxin (-)-gymnodimine (1) has been accomplished in a convergent manner. A highly diastereo- and enantioselective exo-Diels-Alder reaction catalyzed by a bis-oxazoline Cu(II) catalyst enabled rapid assembly of the spirocyclic core of gymnodimine. The preparation of the tetrahydrofuran fragment utilized a chiral auxiliary based anti-aldol reaction. Two major fragments, spirolactam 56 and tetrahydrofuran 55, were then coupled through an efficient Nozaki-Hiyama-Kishi reaction. An unconventional, ambient temperature t-BuLi-initiated intramolecular Barbier reaction of alkyl iodide 64 was employed to form the macrocycle. A late stage vinylogous Mukaiyama aldol addition of a silyloxyfuran to a complex cyclohexanone 83 appended the butenolide, and a few additional steps provided (-)-gymnodimine (1). A diastereomer of the natural product was also synthesized, C4-epi-gymnodimine (90), derived from the vinylogous Mukaiyama aldol addition.

Original languageEnglish
Pages (from-to)19844-19856
Number of pages13
JournalJournal of the American Chemical Society
Volume133
Issue number49
DOIs
Publication statusPublished - Dec 14 2011
Externally publishedYes

ASJC Scopus subject areas

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

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