Studies toward the total synthesis of azaspiracid 1

A synthetic approach to the C₁-C₂₀ portion of the initially proposed structure of Azaspiracid 1 is described. The monoanomeric bisspiroketal configuration is controlled via a metal chelate between the C₉ hydroxyl and the C₁₃-C₁₇ pyran oxygen. The convergent synthesis strategy relied on a modified Ju...

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Bibliographic Details
Main Author Raymer, Brian Kenneth
Format Dissertation
LanguageEnglish
Published S.l. : s.n. 2004
Subjects
Azaspiracid-1 synthesis
Marine pharmacology
Marine toxins > Synthesis
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Summary:A synthetic approach to the C₁-C₂₀ portion of the initially proposed structure of Azaspiracid 1 is described. The monoanomeric bisspiroketal configuration is controlled via a metal chelate between the C₉ hydroxyl and the C₁₃-C₁₇ pyran oxygen. The convergent synthesis strategy relied on a modified JuliaKocienski olefination to append the C₁-C₄ sidechain and an acetylide as a two-carbon linker to join the C₁-C₁₀ and C₁₃-C₂₀ regions. Key stereoselective transformations include a homoaldol addition, a directed reduction, a cyclic acetal reduction, and an acyclic alkylation. Construction of the C₁-C₁₀ and C₁₃-C₂₀ portions began from copper-catalyzed asymmetric hetero-Diels-Alder and ene reactions, respectively.