Synthesis Of Phenylpropanoic Acid Derivatives

Danshen (Salvia miltiorrhiza Bunge) was first recorded in the Shen Nong Ben Cao Jing. It has the special effects on cardiovascular and cerebrovascular diseases. Danshensu which is named3,4-dihydroxyphenyl lactic acid is main active component of Danshen extract. It belongs to the phenylpropanoic acid derivatives. The content of danshensu in Danshen is low and its purification is difficult. In addition, the danshensu is a highly water-souble compound, the bioavailability is low and the half-life is very short in vivo. These properties limit the application of danshensu in clinical. Chemical synthesis can provide an alternative way to get danshensu and structure modification may obtain the superior derivatives. In this thesis, the danshensu was used as a lead compound to design and synthesize phenylpropanoic acid derivatives.The strategy to synthesize phenylpropanoic acid derivatives was designed to use aromatic aldehyde and N-acetyl glycine as starting material. After condensation reaction, the formed benzyloxazole was reduced and hydrolyzed to give topic compounds. Based on the above strategy,10benzyloxazoles were obtained. In order to obtained chiral product, the chiral catalyst is needed in the reductive reaction. Therefore,12chiral thiourea catalysts were synthesized. Hantzsch ester1,4-dihydropyridine was used as reducing reagent, chiral thiourea derivative was used as catalyst,10phenylpropanoic acid derivatives were obtained through reduction of benzyloxazole.Using microbial transformation for asymmetric synthesis of phenylpropanoic acid derivatives was explored. The acetophenone and diethyl oxalate were used as starting material. The substrate was obtained by condensationreaction. Preliminary tests showed that the substrate was reduced by whole Baker’yeast.