Synthesize And Study On The β-lactam Derivatives Of 1,5-benzothiazepine

1,5-benzothiazepine is a kind of compound which has important physiological activities. Some of his derivatives have been used in clinic as antianxiety drug, hyprosis and cardiovascular medicine. Therefore, his syntheses, structures and pharmacological activities have attracted wide attentions. The C=N double bond in the molecules can modify the benzothiazepine which is one of the major parts where chemical reactions occurred. Thus a series of new 1,5-benzothiazepine derivatives have been synthesized and developed. Our group have been doing extensive studies on their [2+2] cycloaddition reactions. In this thesis, we have obtained a series of new β -lactam derivative of the 1,5-benzothiazepine through the reaction of the potassium salt of malicmide which is activated by ClCOOEt and the 1,5-benzothiazepine. The spectrum was analyzed and studied. Our work is important to find their special functions and new active chemical compounds of physiology.1.Start from (DL)- malic acid, then follow the next four reaction steps, such as esterification, carboxyl protection, we get the malic anhydride which is used as the -NH2 protection agent of amino acid reacted with amino acid. Through this reaction, we get malicmide acetic acid and develop its six reaction conditions. We also find its optimum reaction conditions.2.Firstly we let the potassium salt of malicmide protected with carboxyl react with the ClCOOEt which is used as the activator in this reaction. Secondly, we let the production react with the C=N of the benzothiazepine under the surrounding of Et3N solution, so we obtain a series of new 3 -lactam derivatives of the 1,5-benzothiazepin.The structures of the production are determined by IR, 1H NMR, MS and elementary analysis.3.We substitute (DL)-malic acid for (S)-macid acid and synthesize the malic anhydride protected with carboxyl which has the optic properties. We go on the same steps as the above, that is let the malic anhydride react with 1,5-benzothiazepin to get the β -lactam derivative of the 1,5-benzothiazepine which has the optic properties and lay the foundation of the synthesis of the benzothiazepine which has the optic properties.