| This paper is made up of the synthesis of a-difluoromethy-ornithine hydrochloride and the quinapril hydrochloride.The first part is on the synthesis of the a-difluoromethy-ornithine hydrochloride(DFMO). Whose chemical name is 2,5-diamino-2-(difluoromethyl) pentanoic acid hydrochloride. It was discovered with excellent biological activity in last century. Difluoromethy-arnithine hydrochloride has been used as a new type remedy for terminal cancer patients. A general approach to the preparation of a-halogenomethyl-a-amino acids which are potential enzyme-activateed irreversible inhibitors of the parent a-amino acid decarboxylases is described. We employed a-orithine as raw materials, including a series of reaction, protection of amino, esterification, alkylation and removal of the protecting groups . The key step in the synthesis is the regioselective alkylation of a Schiff base readily available from the parent a-amino acid. In the route we used chlorodifluoromethan to give the corresponding a-halogenomethylated adduct. Subsequent removal of the protecting groups from the adduct upon acidic treatment yields the corresponding a-halogenomethyl-a-amin acids. The mechanism of the key alkylation reaction appears to depend on the degree and the nature of the substitution of the halomethanes, it is suggested that chlorodifluoromethan react via an SN2 type mechanism. On the synthesis of the a-difluoromethy-ornithine hydrochloride , the operation is simple and all raw materials are cheap and friendly to the environment, so the route is suited for industrialization. Its structure was confirmed by IR, NMR, MS.The other part is on the synthesis of the quinapril hydrochloride, whose chemical name is (S)-2-((S)-2-((S)-l-ethoxy-l-oxo-4-phenylbutan-2-ylamino) propanoyl)-l,2,3,4-tetrahyoisoquinoline-3-carboxylic acid hydrochloride, It is the product of the Warner-Lambert company for treatment of hypertensive. The development of anti-hypertensive agents was briefly introduced in this paper, and the mechanisms of Quinapril, the third generation angiotensin converting enzyme inhibitor, was also introduced. The synthesis of Quinapri was studied importantly. Lots of methods for the synthesis of the quinapril hydrochloride have low yield and are protected by patent. So we designed a simple and new one, which employed L-phenyalanine and L-alanine as raw materials . Including the preparation of side chain, we got the quinapril hydrochloride by six steps. A new synthetic route was designed and the process was investigated and improved to make easier, and the yield was elevated. All the work provide the foundation for its industrialization. The structures of the products were characterized by IR, NMR. |
