丹参素是中药丹参中水溶性有效成分之一，药理学实验表明其具有抗癌、抗动脉粥样硬化、抗氧化和保护心肌等活性。但是由于丹参中丹参素的含量低(仅为0.5%)且其结构具有不稳定性，因此丹参素及其衍生物的化学合成具有研究价值。另外氨基酸具有丰富的营养作用、免疫调节作用和抗肿瘤活性等。本课题运用药物拼合原理设计并合成丹参素酰胺类抗血栓先导化合物。 本实验首先以原儿茶醛为起始物，依次和N-乙酰甘氨酸经Knoevenagel缩合反应、酸水解、不对称还原和成盐反应最终合成丹参素钠。然后运用亚硫酰氯法分别将苯丙氨酸、亮氨酸、蛋氨酸和天门冬氨酸与甲醇(乙醇)制得其相应的氨基酸甲(乙)酯盐酸盐形式。最后尝试将丹参素钠与氨基酸酯盐酸盐在多种酰胺键成键缩合试剂(DCC/DMAP、NMM/IBCF、EDCI/HOBt、EDCI/DMAP)作用下合成新型丹参素-氨基酸酰胺类衍生物。运用EDCI/DMAP分别合成丹参素与苯丙氨酸甲(乙)酯、亮氨酸甲酯、蛋氨酸甲酯和天门冬氨酸二甲酯的5种酰胺类衍生物，其化学结构均已通过1H NMR表征确认。 最后考察丹参素及其酰胺类衍生物对SD大鼠急性血瘀模型血液流变学相关指标(ηb和RI)的影响。采用大鼠皮下注射Adr和冰水浸泡以复制急性血瘀模型，再分别灌胃给予丹参素及其衍生物和阳性对照药CDDP干预，观察其对ηb和RI的影响。实验结果表明丹参素-亮氨酸甲酯酰胺类化合物(12)在改善血液流变学相关指标方面要优于丹参素和丹参素-苯丙氨酸甲酯酰胺类化合物(10)。

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 rats were investigated. The model can be duplicated after the treatment of adrenaline injected subcutaneously and ice-water bath, then DSS and its derivatives as well as positive control CDDP were administered respectively to test their influences on ηb and RI. Experimental results have shown that compound 10 has an advantage of improving hemorheology-related indicators over DSS and compound 12.