An Optimization Of Synthetic Route Toward Monosubstituted Diethyl Malonate Derivates

Malonic acid is an essential precursor in organic synthesis and biosynthesis.Diethyl malonate,the diethyl ester of malonic acid,is commonly used to synthesize barbital in medicinal chemistry.Amino acid,coumarin and nicosulfuron can also synthesized by diethyl malonate.In biochemistry,malonyl-coenzyme A(CoA),the CoA derivative of malonic acid,can anabolism fatty acid.Moreover,malonic acid derivates can be used to explore the biosynthesis of polyketides,which are an important class of bioactive secondary metabolites.Malonic acid derivates such as methylmalonic acid,ethylmalonic acid can also explore the biosynthesis of polyketides.There are three different kinds of polyketide synthase: type Ⅰ,type Ⅱ and type Ⅲ polyketide synthase.The common PKS natural products including Rifamycin,tetracycline,aloesone,resveratrol,epothilone and doxorubicin.Based on its structure,antimicrobial,antioxidant activity;antitumor and anti-inflammatory activity.So,synthesis of single substituted diethyl-malonate derivates can explore the biosynthesis of polyketides.Based on diethyl 2-ethylmalonate,in the process to synthesize mono bromosubstituted diethyl malonate derivates,there are no effective way to overcome the cyclization condition.Here,we report a novel strategy with a multistep process to synthesize mono bromo-substituted diethyl malonate derivates.Acetylation of hydroxy makes the reaction possible and productive;Hydrolyzation and esterification let this process touchable;with a perfect ending with halogenation.Affinity-based Probe are synthesized to investigate the process of polyketides.This work provides the basis to further explore the biosynthesis of polyketides.