Synthesis of Cinnamic Acid Esters As Potential Platelet Aggregation Inhibitor

• Main Authors: Yu-Ya Hung, 洪玉雅
• Other Authors: Chi-Ming Chen
• Format: Others
• Language: zh-TW
• Published: 1993
• Online Access: http://ndltd.ncl.edu.tw/handle/30441416348909231878

碩士 === 台北醫學院 === 藥學研究所 === 81 === Cafeetannins 及 polyphenolic caffeoylquinic acid 之衍生物,其廣泛 分佈於植物中,其中一種活性成分methyl 3,4-dicaffeoyl- quinate被發 現具強烈的抑制血小板凝集作用和抑制人類血小板throm- boxane之生合 成.為了評估其化學構造與血小板凝集及 thromboxane 之生成抑制作用關 係,擬以 methyl 3,4-dicaffeoylquinate 為化學合成目標, 製備多種類 似化合物.我們利用 cinnamic acid, 3,4-dimethoxycinnamic acid, 3,4- methylenedioxycinnamic acid and caffeic acid 之 acyl chlorides 和一系列 aliphatic alcohols 和 phenolic　alcohols 反應 而得 22 種產物. 1,3-dicinnamoylpropanediol (1), 1,3-di(3',4'- dimethoxy- cinnamoyl)propanediol (2), 1,3-di(3',4'- methlenedioxycinnamoyl) propanediol (3), 1,2-dicinnamoylpropanediol (4), 1,2-di(3',4'- dimethoxycinnamoyl)propanediol (5), 1,2-di(3',4'- methylenedioxy- cinnamoyl)propanediol (6), 1,2-dicinnamolcyclohexanediol (7), 1,2-di(3',4'- dimethoxycinnamoyl)cyclohexanediol (8), 1,2-di(3', 4'-methylenedioxycinnamoyl)cyclohexanediol (9), 1,2-dicinnamoyl- glycerol (10), 1,2-di(3',4'-dimethoxycinnamoyl) glycerol (12), methyl 3,4-dicinnamoylbenzoate (13),methyl 3,4-di(3',4'-methoxy- cinnamoyl)benzoate (14), methyl 3,4-di(3',4'-methylenedioxycin- namoyl)benzoate (15), methyl 3,4,5-tricinnamoylgallate (16), methyl 3,4,5-tri(3',4'- dimethoxycinnamoyl)gallate (17), methyl 3,4,5-tri(3',4'- methylenedioxycinnamoyl)gallate (18), methyl 3,4-dicinnamoyl-5- methoxybenzoate (19), methyl 3,4-di-(3',4'- dimethoxycinnamoyl)-5-methoxybenzoate (20), methyl 3,4-di(3',4'- methylenedioxycinnamoyl)-5-methoxybenzoate (21), 1,3-dicaffeoyl- propanediol (22).此 22 種目的化合物經紅外光譜, 氫譜, 碳譜及質譜光譜分析確定其化學結構, 其有關血小板凝集抑制之藥 理作用正在試驗中. Cafeetannins are naturaly occurring polyphenolic caffeoyl- quinic acid derivatives.One of these compounds, methyl 3,4-dic- affeoylquinate,was found to be inhibitory toward platelet aggr- egation and thromboxane biosynthesis on human platelet. Therefore, several analoques modeled after methyl 3,4-dicaffeoylquinate were prepared by chemical synthesis in order to evaluate the relationship between their structures and antiplatelet and the thromboxane formation inhibitory activity. The acyl chloride derivatives of the substituted cinnamic acids, were reacted with a series dihydroxyl or trihydroxyl compounds of alcohols and phenols to yield 22 cinnamic acid esters. They are 1,3-dicinnamoylpropanediols (1),(2) and (3) , 1,2-dicinnamoylpropanediols (4),(5) and (6),1,2-dicinnamoyl- cyclohexanediols (7),(8) and (9),1,2-dicinnamoylglycerol (10), (11) and (12),methyl 3,4-dicinnamoylbenzoates (13),(14) and (15) , methyl 3,4,5-tricinnamoylgallates (16),(17) and (18), methyl 3,4-dicinnamoyl-5-methoxybenzoates (19),(20) and (21), 1,3-dicaffeoylpropanediol (22). The structures of these 22 compounds are consistant with the spectral data (UV, IR, PMR, CMR and Mass). The evaluation of platelet aggregation inhibitory activity is under investi- gated.