The Asymmetric Synthesis And Process Optimization Of PKC Regulator V8

Protein kinase C(PKC)is the effect material in GPCR system as the multifunctional tyrosine and serine kinase,which distributes widely in many human organs and plays an important role in the process of signal transduction of the body.There are three kinds of PKC discovered so far according to their activation modes,including 11 subtypes.The common structure of PKC is consist of a single peptide chain whose basic structure units are divided into four highly homologous conservative areas and five low homologous variable areas.A multitude of studies manifest that PKC is closely related with tumor growth,diabetic nephropathy,gastrointestinal disease,Alzheimer’s disease and heart disease.It’s one of the hottest topics to realize the therapy of the related diseases through the regulation of PKC activity.Benzolactams-V8 can regulate the activity of PKC strongly and also has a better selectivity for its subtypes.In this thesis,we designed an asymmetric synthesis route for Benzolactams-8 and optimized the process.The target molecule was obtained in 37%total yield from the material o-nitrotoluene after 12 linear steps.The features of this synthesis are the ready availability of starting material,the avoiding of chromatography,the excellent stereoselectivity of some key steps,goodatom economy,which means that this methold holds the potential for an industrial production of Benzolactams-V 8.