Synthesis Of ?,?-unsaturated Esters And ?-ketone Esters With Amino Acid Ester-Derived Katritzky Salts&Design And Synthesis Of Bisubstrate Inhibitors Of NNMT

Amino acids and their derivatives are not only widely distributed in organic molecules and natural products,but also important components of many bioactive substances and building blocks for organic synthesis.Bench-stable and easily handled redox-active Katritzky salts can be easily prepared from amino acids.As part of this work,we synthesized a series of ?,?-unsaturated esters and y-ketone esters in moderate to good yields upon irradiation with household blue LEDs,using Ru(bpy)3Cl2·6H2O as photocatalyst,K2CO3 as base,Katritzky salt as radical precursor.The reaction provides a new synthetic route for ?,?-unsaturated esters and y-ketone esters,which displays an excellent functional group tolerance and a potential utility for amino acids functionalization.Nicotinamide N-methyltransferase(NNMT)is an important methylase and plays an important role in vivo.However,overexpression of NNMT has been found in many cancers.Therefore,NNMT may be a potential therapeutic target with abnormally high expression in various diseases.Nevertheless,so far only a few NNMT inhibitors have been reported.Based on the design,synthesis and bioactivity characterization of NNMT bisubstrate inhibitors MS2734(6)and MS2756(7),we further designed a series of possible NNMT bisubstrate inhibitors.By retrosynthetic analysis,the target compound can be divided into three building blocks.By convergent synthesis strategy,the amino acid derivatives and adenosine derivatives building blocks react to obtain common intermediates,and then react with various phenylethylamine derivatives building blocks to synthesize our target compound.The biological inhibitory activity was also determined and satisfactory results were obtained.