RESUMEN
Total synthesis of asterelin A was accomplished by applying intramolecular Suzuki-Miyaura and oxidative couplings to the formation of an 18-membered macrocyclic ring and a dibenzofuran, respectively.
Asunto(s)
Benzofuranos/síntesis química , Compuestos Macrocíclicos/síntesis química , Acoplamiento OxidativoRESUMEN
Eight new clerodane type diterpenoids, named 7-oxo-kolavelool (1), 7alpha-hydroxykolavelool (2), 6alpha,7alpha-dihydroxykolavenol (3), 12-oxo-hardwickiic acid (4), ptycholide I (5), ptycholide II (6), ptycholide III (7), and ptycholide IV (8) were isolated from the MeOH extract of the bark of a Brazilian medicinal plant, Ptychopetalum olacoides. The structures of 1-8 were elucidated by analyzing spectroscopic data and by comparing their NMR data with those of the previously reported compounds kolavelool (la), kolavenol (3a), hardwickiic acid (4a), and ptychonolide (5a). Compounds 5 and 6 existed as a 1:1 mixture of inseparable epimers at C-15.
Asunto(s)
Diterpenos de Tipo Clerodano/química , Diterpenos/química , Olacaceae/química , Dicroismo Circular , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Conformación Molecular , Corteza de la Planta/química , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Infrarroja , Espectrofotometría UltravioletaRESUMEN
From the MeOH extract of Ptychopetalum olacoides, which is used in Brazilian folk medicine for the treatment of chronic degenerative conditions of the nervous system, four novel clerodane-type diterpenoids named 6alpha,7alpha-dihydroxyannonene (1), 7alpha,20-dihydroxyannonene (2), 7alpha-hydroxysolidagolactone I (3), and ptycho-6alpha,7alpha-diol (4) were isolated by bioassay-directed fractionation using NGF-differentiated PC12 cells. The structures of 1-4 were established by extensive NMR spectroscopic analyses and chemical conversion. Compounds 1 and 2 significantly enhanced NGF-mediated neurite outgrowth in PC12 cells at concentrations ranging from 0.1 to 50.0 microM for 1 and 0.1 to 30.0 microM for 2, whereas 3 and 4 had no morphological effect on NGF-mediated PC12 cells in the same concentration range. The structure-activity relationship of these compounds is also discussed.
Asunto(s)
Diterpenos/química , Factor de Crecimiento Nervioso/metabolismo , Olacaceae/metabolismo , Plantas Medicinales/metabolismo , Animales , Bioensayo , Diferenciación Celular , Diterpenos de Tipo Clerodano/química , Sinergismo Farmacológico , Espectroscopía de Resonancia Magnética , Conformación Molecular , Neuritas/metabolismo , Células PC12 , Plantas Medicinales/química , Ratas , Espectrofotometría Infrarroja/métodosRESUMEN
Riccardin C, a nuclear receptor LXRalpha selective agonist, is an 18-membered macrocyclic bisbibenzyl isolated from several liverworts. Synthesis of riccardin C and its seven O-methylated derivatives was accomplished. The synthetic sequence highlights an intramolecular Suzuki-Miyaura coupling in the formation of the 18-membered biaryl linkage present in riccardin C. The structure-activity relationship of these compounds suggests that all of the phenolic hydroxy groups present in riccardin C are essential for the activation of LXRalpha.
Asunto(s)
Química Farmacéutica/métodos , Éteres Cíclicos/síntesis química , Éteres Cíclicos/farmacología , Receptores Nucleares Huérfanos/antagonistas & inhibidores , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Humanos , Receptores X del Hígado , Modelos Químicos , Estructura Molecular , Fenol/química , Espectrofotometría/métodos , Relación Estructura-ActividadRESUMEN
Four new clerodane-type diterpenoids, ptychonolide (1), 20-O-methylptychonal acetal (2), and an equilibrium mixture of ptychonal hemiacetal (3) and ptychonal (4), were isolated from the MeOH extract of the bark of a Brazilian plant, Ptychopetalum olacoides. The structure of 1 was elucidated as a clerodane-type diterpenoid on the basis of spectroscopic data, whereas 2 was assigned to an acetal derivative of 1. Compounds 3 and 4 existed as an equilibrium mixture. A mixture of compounds 3 and 4 was found to exhibit neurite outgrowth-promoting activities on NGF-mediated PC12 cells at concentrations ranging from 0.1 to 10.0 microM.