Total synthesis and structural elucidation of azaspiracid-1. Construction of key building blocks for originally proposed structure

K. C. Nicolaou, Petri M. Pihko, Federico Bernal, Michael O. Frederick, Wenyuan Qian, Noriaki Uesaka, Nicole Diedrichs, Jürgen Hinrichs, Theocharis V. Koftis, Eriketi Loizidou, Goran Petrovic, Manuela Rodriquez, David Sarlah, Ning Zou

Research output: Contribution to journalArticlepeer-review

Abstract

Syntheses of the three key building blocks (65, 98, and 100) required for the total synthesis of the proposed structure of azaspiracid-1 (1a) are described. Key steps include a TMSOTf-induced ring-closing cascade to form the ABC rings of tetracycle 65, a neodymium-catalyzed internal aminal formation for the construction of intermediate 98, and a Nozaki-Hiyama-Kishi coupling to assemble the required carbon chain of fragment 100. The synthesized fragments, obtained stereoselectively in both their enantiomeric forms, were expected to allow for the construction of all four stereoisomers proposed as possible structures of azaspiracid-1 (1a-d), thus allowing the determination of both the relative and absolute stereochemistry of the natural product.

Original languageEnglish (US)
Pages (from-to)2244-2257
Number of pages14
JournalJournal of the American Chemical Society
Volume128
Issue number7
DOIs
StatePublished - Feb 22 2006
Externally publishedYes

ASJC Scopus subject areas

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

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