An Important Intermediate For The Synthesis Of Ace Inhibitors And Asymmetric Michael Reaction

Angiotensin Converting Enzyme Inhibitors(ACEI), which have been developed rapidly in recent years, are a series of medicines for treating cardiovascular and cerebrovascular diseases. They have been recommended by the World Health Organization as important antihypertension medicines for their special pharmacological action and excellent curative effect. Of these medicines, the kind of N-carboxyl alkyl dipeptide has promising future. In this thesis, the method of the synthesis of the common intermediate compound(l)of this style has been further studied. It is confirmed a procedure for esterifying the alanine. Thus the ester which can be employed in the reaction is limited to esters such as benzyl ester of tert-butyl ester, which are prepared by a relatively complicated procedure. By using this route, the complexity of the reaction has been reduced and the process of the post-disposal has become simpler.In the reaction, by using Michael addition with alkali as protective, utilizing a-alanine's N of chiral carbon to introduce N+ lof chiral carbon of the new compound, and making use of the different solubility of resultant in the solvent, disparting (S,S) form dominical compound. We avoided the separation of enantiomer and taking off protective , optimized the conditions of the series of reactions. At the same time, brought forward the inner salt creation in the first time, corrected the literature draw doubt conclusion.In the aspects of asymmetric Michael addition reaction, firstly, we studied the Michael addition reactions of the other alanine and ethyl acrylic benzoylacrylate, put forward the new purificiation method, increased the products' purity, synthesized two series of eight kinds of new asymmetric compounds. Five new compounds' structures of which were characterized by elemental analysis , IR, 1HNMR and MS. The rest of three compounds hadn't good solubilityin the solvent. This method can be used not only in the preparation of ACEI medicine intermediates, but also as a kind of simple and important method in increasing dissymmetry carbon atom quantity and extending carbon chain.On this foundation, we did the further research about the Michael addition reaction of alanine and ethyl acrylic benzoylacrylate with substituted groups. And we draw accidental conclusion that different substituted groups can carry out Michael reaction , the ethyl acrylic benzoylacrylate with supply electron groups can reduce the yield. In the process of synthesizing isopropyl benzoyl acrylic acid, we should have a unsaturated acid ,but discovered a saturated carboxylic acid. Further more, the structure of the products were characterized by IR and 1HNMR.