丹参素-氨基酸酰胺类衍生物的合成及初步药理学研究-化学工程专业论文.docx

万方数据 万方数据 Subject: The Synthesis and Preliminary Pharmacological Studies of Danshensu-Amino acid Amide Derivatives Specialty: Chemical Engineering Name: Gao Yongfei (Signature) Instructor: He Shihua (Signature) Chen Fuxin (Signature) Wang Xinwei (Signature) ABSTRACT Danshensu(DSS) is one of active water-soluble component in Danshen, it exhibits diverse pharmacological activities such as anti-cancer, anti-atherosclerosis, anti-oxidation, cardioprotection. However, because of relatively low content in Danshen(0.5%) and structural distability, the chemical synthesis of DSS and its derivatives possess research value. Moreover amino acids have plentiful activities as well such as trophism, immunoregulation and anti-tumor. On the basis of Medicinal Chemistry Hybridation, several amide between DSS and amino acids derivatives have been designed and synthesized. In addition, the effects of DSS and its derivatives on hemorheology in acute blood stasis model of rats were investigated. DSS-sodium was synthesized from protocatechualdehyde by the reactions of Knoevenagel condensation, hydrolization, asymmetric reduction and salt-forming. Then the corresponding amino acids methyl(ethyl)esters hydrochloride were obtained via thionyl chloride methods through the reaction between phenylalanine, leucine, methionine, aspartic acid and methanol(ethanol). Finally, we try to Danshensu Sodium and amino acid ester hydrochloride in a variety of the amide bond a bond coupling reagent (DCC/DMAP, NMM/IBCF, EDCI/HOBt, EDCI/DMAP) synthesis of a new type of DSS-amino acid amide derivatives. The use of EDCI/DMAP respectively synthesis of Danshensu and phenylalanine methyl (ethyl) ester, leucine methyl ester, methionine methyl ester and aspartic acid dimethyl ester five amide derivatives, their chemical structures have passed characterized by 1H NMR confirmed. Finally, the effects of DSS and its amide derivatives on hemorheology-related indicators(ηb and RI) in acute blood stasis model of ra