Two Compounds Of The Preparation And Development Of Important Medicinal Value

D-phenylalanine and Allopurinol have been widely applied in the pharmaceutical field. D-phenylalanine is an important composition of inhibitor of the AIDS virus. It can also be used as the raw material of antitumor, antidiabetics and enkephalinase inhibitors. Allopurinol is the first choice in the treatment of gout, and it was applied to treatment of leukemia and nephropathy. Allopurinol is also an important intermediate in syntheses of antitumor and cardiovascular agent. In this paper the preparation of D-phenylalanine by asymmetric transformation and synthesis of allopurinol were studied respectively.D-phenylalanine: D-phenylalanine·D-tartaric acid was synthesized by reaction of DL-phenylalanine and D-tartaric acid in the presence of salicylaldehyde in propionic acid. The influences of reaction conditions such as resolution agent, reaction temperature, reaction time, catalyst etc were studied and proper conditions were established. The structure of D-phenylalanine·D-tartaric acid was confirmed by IR-spectrum,1H NMR-spectrum and elementary analysis. D-phenylalanine·D-tartaric acid was treated with triethylamine in ethanol giving D-phenylalanine with 98% optical purity in 69% yield. The structure of D-phenylalanine was confirmed by specific optical rotation and IR-spectra. Circular utilization of mother liquor and recovery of resolution agent have been also studied. The experiments were amplified to six times and the simple workmanship process has been designed.Allopurinol: The formation mechanism of allopurinol was discussed. Ethoxyl-methylene-cyanacetic ethyl ester was synthesized by condensation of ethyl ortho formate and cyanacetic ethyl ester. Cyclization reaction of the condensation product with hydrazine hydrate and formamide in the presence of acid gives allopurinol. The influences of temperature, time, catalyst and the ratio of material on the reaction were studied. Ethyl ortho formate, cyanacetic ethyl ester, acetic anhydride (molar ratio: 2 : 1 : 2) and zinc chloride (catalyst) were heated at 110-120oC, 130-140oC for 2 hours and 2 hours, respectively. The reaction mixture was distilled in vacuo and ethoxyl-methylene-cyanacetic ethyl ester was collected at 140-142oC/2mmHg in yield of 89.6%. The product was confirmed by melting point and boiling point.Allopurinol was synthesized by one-step cyclization reaction in the presence of acid. The influences of temperature, time and catalyst were studied. The crude product of allopurinol was prepared by heating ethoxyl-methylene-cyanacetic ethyl ester, hydrazine hydrate and excess formamide at 118oC, 130oC, and 150oC for 1 hour, 1hour, and 8 hour respectively. The crude product was re-crystallized in water to give fine allopurinol with purity 100% in the yield of 40%. The simple workmanship process has been designed.