Synthesis Of New 1,5-benzothiazepines Containing 2-pheny1-1,2,3-triazol And Their Derivatives

The I ,5-benzothiazepines are a kind of seven-membered ring heterocyclic compounds which possess many physiological properties. They are often used as tranquilizer and medicines for cardiovascular disease. It has been shown in recent research that the pharmacological activities of parent molecules will apparently be improved with introduction of 1 ,2,3-triazole ring into some active molecules: Penicillin, Cephalosporins and so on. In previous literatures, the research of 2 or 4-heterocycle substituted 1 .5-benzothiazepines is seldom. Therefore, we expect to realize reinforcement of many physiological activities by means of combining the new group, 2-phenyl- 1 .2.3-trizol with 1 .5-benzothiazepine. In addition, we combined 13 -Iactam, I ,2,4-oxadiazole and I ,2,4-triazole moieties which have strong biological activities with I ,5-benzothiazepines containing 2-phenvl- 1,2,3 - triazol by [2+2] cycloaddition and 1,3-dipolar cycoladdition reaction respectively, and a series of derivatives with novel structures were synthesized. The thesis includes two major parts: The first part is about literature review The important synthetic methods, structure and chemical transformation of 1 .5-benzothiazepine derivatives that have been studied in China and other countries were explicated systematically. The second part is about the experimental content. Major work as follows: We synthesized 2-phenyl-1,2,3-triazo]-4-carboxaldehyde from glucose via ? glucosazone-forming, ring-closing and oxidation. The aldehvde obtained reacted with acetophenone or para-substituted acetophenones to form chalcones(la?le) by aldol condensations And the reaction of chalcones with 2-arninothiophenol gave 1 ,5-benzothiazepines containing 2-phenyl- I ,23-triazol(2a--2e); By treating benzoth- iazepines (2a?e) with ketene, aryl nitrile oxides and benzonitrile N-phenylimine 3 generated in situ respectively undergoing [2+2] cycloaddition and l,3-dipolar cycloaddition reaction, a series of new benzothiazepine derivatives (3a?e, 4a?e, Sa桽e, 6a?e,7a--~7e) were obtained. Above all, thirty-four new compounds were synthesized and their structures were confirmed by elemental analysis,IR, H NMR and MS spectral data. The mass spectrums of some representative compounds were explained in detail. To P -lactam derivatives 3a and 4a,we studied their Nuclear Overhauser Effect(NOE) difference experiments, and their conformation was testified together with analysis of the I vicinal proton-proton coupling constants.