RESUMEN
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].
Asunto(s)
Depsipéptidos/síntesis química , Concentración de Iones de Hidrógeno , Unión Competitiva/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Depsipéptidos/química , Depsipéptidos/farmacología , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Modelos Moleculares , Conformación Molecular , Rianodina/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/efectos de los fármacos , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría Ultravioleta , Estereoisomerismo , Verticillium/químicaRESUMEN
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.