RESUMEN
Fusarochromene isolated from the plant pathogenic fungus, Fusarium sacchari is closely related to a group of mycotoxins including fusarochromanone previously isolated from various Fusaria spp. Despite their assumed polyketide biogenesis, incorporation studies with 13C-labelled acetate, glycerol and tryptophans show that fusarochromene is unexpectedly derived via oxidative cleavage of the aromatic amino acid tryptophan. A putative biosynthetic gene cluster has been identified.
Asunto(s)
Fusarium/metabolismo , Triptófano/metabolismo , Fusarium/genética , Familia de Multigenes/genética , Oxidación-ReducciónRESUMEN
The identification of a new series of RORc inverse agonists is described. Comprehensive structure-activity relationship studies of this reversed sulfonamide series identified potent RORc inverse agonists in biochemical and cellular assays which were also selective against a panel of nuclear receptors. Our work has contributed a compound that may serve as a useful in vitro tool to delineate the complex biological pathways involved in signalling through RORc. An X-ray co-crystal structure of an analogue with RORc has also provided useful insights into the binding interactions of the new series.
Asunto(s)
Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/agonistas , Sulfonamidas/química , Sitios de Unión , Supervivencia Celular/efectos de los fármacos , Cristalografía por Rayos X , Citocinas/biosíntesis , Agonismo Inverso de Drogas , Células HEK293 , Humanos , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Simulación de Dinámica Molecular , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/antagonistas & inhibidores , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Unión Proteica , Estructura Terciaria de Proteína , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Sulfonamidas/toxicidadRESUMEN
The total syntheses of the 3,6-dihydroxydecanolide from Cordyceps militaris and the novel C-3 epimer are reported using a diastereoselective Nozaki-Hiyama-Kishi reaction in the key cyclization to generate the 6R stereocenter.