Synthetic Research Of ACE Inhibitor Moexipril Hydrochloride

Moexipril hydrochloride, which belongs to a new generation of ACE inhibitors containing carboxyl as an active group, is indicated for the treatment of hypertension. Moexipril hydrochloride is an effective and long-term active antihypertension drug. Through oral Moexipril hydrochloride once daily, the blood pressure can be controlled during 24 hours.In this paper, synthesis of moexipril hydrochloride is studied. Hippuric acid and veratraldehyde are reported as the starting material in preparation of moexipril hydrochloride. After several steps, (S)-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid, phenylmethyl ester are prepared, the latter reacting with N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanine gets moexipril phenylmethyl ester. After hydrogenation, moexipril hydrochloride was prepared. From veratraldehyde, the overall yield of moexipril hydrochloride is 21.6% as reported.In our study, some alternative ways have been introduced to improve the whole process of manufacture of moexipril hydrochloride.In preparation of (S)-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid, Optical resolution was taken instead of asymmetric hydrogenation. The resolution route is an economical and available way in the large scale manufactory. It costs several folds less than asymmetric hydrogenation route.In the course of synthesis of moexipril phenylmethyl ester, the starting material N-[(S)-1-ethoxycarbonyl- 3-phenylpropyl]-L-alanine was changed into its active anhydride -NCA. The yield of this step has been raised largely (84.8% vs. 65%), and the route we taken is more effective and economical. Another advantage of this route is that waste residue has been avoided mostly.After several improvements, the new route of preparation of moexipril hydrochloride has been an economical and effective one, which may be more approach to the large scale manufactory than that reported before.