Dihydropyridine Derivatives

This paper was divided into two chapters, the first chapter was the synthesis of dihydropyridine (DHP) derivatives of Calcium antagonists(CCB).Calcium antagonists also can be named Calcium channel blockers, which is a kind of drugs with broad vascular pharmacological effects. In order to decrease the concentration of Ca²⁺, CCB selectively block Ca²⁺ into cells on the level of channels. Dihydropyridines were only a type of CCB. It is found that DHPs of Calcium antagonists not only can treat hypertension and angina pectoris, but also have the ability of antiatherosclerosis, antiplatelet aggregation and cardiovascular protection. However, the method of solid phase grinding has been used in the synthesis of DHPs derivatives, which owns many advantages: first, it not only can cut down the cost, but also can avoid the environmental pollution caused by organic solvents;second, the reaction occurs soon without solvents, these reactions can be completed in room temperature by grinding without heating;third, the method is in wide general use in recent years for simple process after reaction, which can leave out troublesome steps of organic solvent recycle. In this paper, eight new dihydropyridines derivatives were synthesized by solid phase grinding from 1,3-cyclohexanedione, ethyl acetolacetate,NH₄HCO₃ and different aldehydes. They have been characterized by ¹HNMR and IR, which lay the foundation of further development of this kind of new drugs. The second chapter was the synthesis of NADH mimics. In this chapter, three synthesis routes were studied, in the first route, 1,4-DHPs derivatives with 4-chiral unit as NADH bioasymmetric reducing agents by hydrolysis , ammonofication from geniposide. In the second route, the DHPs derivatives synthesized in the first chapter and chiral phenproamine suppling chiral unit were reacted , to gain NADH biomimics. In the third route, DHPs derivatives were synthesized from chiral lysine hydrochloride , 1,3-cyclohexanedione and ethyl acetolacetate. It is probable to gain 1,4-DHPs derivatives with 1-chiral unit as NADH biomimics. Those three synthesis routes were studied in the laboratory.