RESUMEN
Covering: 2005 up to 2020Olive bioactive secoiridoids are recognized as natural antioxidants with multiple beneficial effects on human health. Nevertheless, the study of their biological activity has also disclosed some critical aspects associated with their application. Firstly, only a few of them can be extracted in large amounts from their natural matrix, namely olive leaves, drupes, oil and olive mill wastewater. Secondly, their application as preventive agents and drugs is limited by their low membrane permeability. Thirdly, the study of their biological fate after administration is complicated by the absence of pure analytical standards. Accordingly, efficient synthetic methods to obtain natural and non-natural bioactive phenol derivatives have been developed. Among them, semi-synthetic protocols represent efficient and economical alternatives to total synthesis, combining efficient extraction protocols with efficient catalytic conversions to achieve reasonable amounts of active molecules. The aim of this review is to summarize the semi-synthetic protocols published in the last fifteen years, covering 2005 up to 2020, which can produce natural olive bioactive phenols scarcely available by extractive procedures, and new biophenol derivatives with enhanced biological activity. Moreover, the semi-synthetic protocols to produce olive bioactive phenol derivatives as analytical standards are also discussed. A critical analysis of the advantages offered by semi-synthesis compared to classical extraction methods or total synthesis protocols is also performed.
Asunto(s)
Iridoides/síntesis química , Olea/química , Aldehídos/síntesis química , Monoterpenos Ciclopentánicos/síntesis química , Glucósidos Iridoides/síntesis química , Glucósidos Iridoides/química , Aceite de Oliva/química , Fenoles/síntesis química , Alcohol Feniletílico/análogos & derivados , Alcohol Feniletílico/síntesis químicaRESUMEN
Catalpol has gained increasing attention for its potential contributions in controlling glycolipid metabolism and diabetic complications, which makes used as a very promising scaffold for seeking new anti-diabetic drug candidates. Acylation derivatives of catalpol crotonate (CCs) were designed as drug ligands of glutathione peroxidase (GSH-Px) based on molecular docking (MD) using Surfex-Docking method. Catalpol hexacrotonate (CC-6) was synthesized using microwave assisted method and characterized by FT-IR, NMR, HPLC and HRMS. The MD results indicate that with the increasing of esterification degree of hydroxyl, the C log P of CCs increased significantly, and the calculated total scores (Total_score) of CCs are all higher than that of catalpol. It shows that CCs maybe served as potential lead compounds for neuroprotective agents. It was found that the maximum Total_score of isomers in one group CCs is often not that the molecule with minimum energy. MD calculations show that there are five hydrogen bonds formed between CC-6 and the surrounding amino acid residues. Molecular dynamics simulation results show that the binding of CC-6 with GSH-Px is stable. CC-6 was screened for SH-SY5Y cells viability by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay, the result indicates CC-6 can effectively reverse SZT induced cells apoptosis with dose-dependent manner, which can indirectly show that CC-6 is a potential neuroprotective agent.
Asunto(s)
Crotonatos/farmacología , Glutatión Peroxidasa/antagonistas & inhibidores , Hipoglucemiantes/farmacología , Glucósidos Iridoides/farmacología , Fármacos Neuroprotectores/farmacología , Sitios de Unión , Encefalopatías/tratamiento farmacológico , Encefalopatías/enzimología , Encefalopatías/etiología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Crotonatos/síntesis química , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/enzimología , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/enzimología , Glutatión Peroxidasa/química , Glutatión Peroxidasa/metabolismo , Humanos , Enlace de Hidrógeno , Hipoglucemiantes/síntesis química , Glucósidos Iridoides/síntesis química , Microondas , Modelos Moleculares , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Fármacos Neuroprotectores/síntesis química , Unión ProteicaAsunto(s)
Aldehídos/química , Diazometano/análogos & derivados , Hidrocarburos Cíclicos/química , Glucósidos Iridoides/síntesis química , Ácidos de Lewis/química , Compuestos de Trimetilsililo/síntesis química , Catálisis , Diazometano/síntesis química , Diazometano/química , Glucósidos Iridoides/química , Estructura Molecular , Estereoisomerismo , Compuestos de Trimetilsililo/químicaRESUMEN
The syntheses of D,L-geissoschizol, D,L-corynantheidol, D,L-dihydrocorynantheol, D,L-protoemetinol, and D,L-3-epi-protoemetinol have been accomplished from a single synthetic intermediate.