RESUMO
The previously accepted structure of the marine toxin azaspiracid-3 is revised based upon an original convergent and stereoselective total synthesis of the natural product. The development of a structural revision hypothesis, its testing, and corroboration are reported. Synthetic (6R,10R,13R,14R,16R,17R,19S,20S,21R,24S,25S,28S,30S,32R, 33R,34R,36S,37S,39R)-azaspiracid-3 chromatographically and spectroscopically matched naturally occurring azaspiracid-3, whereas the previously assigned 20R epimer did not.
Assuntos
Produtos Biológicos/química , Produtos Biológicos/síntese química , Furanos/química , Furanos/síntese química , Piranos/química , Piranos/síntese química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Cromatografia Líquida , Espectrometria de Massas , Estrutura Molecular , Oxirredução , Espectroscopia de Prótons por Ressonância Magnética , EstereoisomerismoRESUMO
A convergent and stereoselective total synthesis of the previously assigned structure of azaspiracid-3 has been achieved by a late-stage Nozaki-Hiyama-Kishi coupling to form the C21-C22 bond with the C20 configuration unambiguously established from l-(+)-tartaric acid. Postcoupling steps involved oxidation to an ynone, modified Stryker reduction of the alkyne, global deprotection, and oxidation of the resulting C1 primary alcohol to the carboxylic acid. The synthetic product matched naturally occurring azaspiracid-3 by mass spectrometry, but differed both chromatographically and spectroscopically.
Assuntos
Produtos Biológicos/química , Furanos/síntese química , Piranos/síntese química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Cromatografia Líquida , Furanos/química , Estrutura Molecular , Oxirredução , Espectroscopia de Prótons por Ressonância Magnética , Piranos/química , Estereoisomerismo , Espectrometria de Massas em TandemRESUMO
An efficient synthesis of the C22-C40 domain of the azaspiracids is described. The synthetic route features a Nozaki-Hiyama-Kishi (NHK) coupling and chelation controlled Mukaiyama aldol reaction to access an acyclic intermediate and a double-intramolecular-hetero-Michael addition (DIHMA) to provide the FG-ring system bridged ketal.