RESUMO
Verticilide (1) is a 24-membered cyclic depsipeptide isolated from the culture broth of Verticillium sp. FKI-1033. It inhibits ryanodine binding to ryanodine receptor (RyR) and has insecticidal activity. The stereochemistry of 2-hydroxyheptanoic acid in verticilide was elucidated by chiral HPLC analysis of the degradation product 6 and synthetic (+) and (-)-6. We also describe the practical total synthesis of verticilide. [reaction: see text].
Assuntos
Depsipeptídeos/síntese química , Concentração de Íons de Hidrogênio , Ligação Competitiva/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Depsipeptídeos/química , Depsipeptídeos/farmacologia , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Modelos Moleculares , Conformação Molecular , Rianodina/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/efeitos dos fármacos , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria Ultravioleta , Estereoisomerismo , Verticillium/químicaRESUMO
Oxopropyl E-(pyrrolidine-2-ylidene)glycinamide (5c) and allyl E-(pyrrolidine-2-ylidene)glycinate (5d) were effectively synthesized from 2,3,5-tri-O-benzyl-4-O-tert-butyldimethylsilyl(TBDMS)-D-arabinal (7) using intramolecular 1,3-dipolar cyclic reaction of azide and olefin as a key reaction. These results proved this cyclic reaction should be applicable for the synthesis of various (pyrrolidine-2-ylidene)glycinate and glycinamide. In addition, the development of a synthetic route for the precursor of an unsaturated cyclic dehydro amino acid involved in azinomycins (carzinophilin) using relating glycinate, methyl E-(pyrrolidine-2-ylidene)glycinate (5a) was described.
