Ace Inhibitors - The Synthesis Process Of The Fosinopril Study

The action mechanism,development,recent advances,clinic application and market outlook of the angiotensin-converting enzyme(ACE)inhibitor are briefly reviewed in this thesis.We introduced fosinopril specially,which is one of the representatives of the third generation ACE inhibitors,evaluated and studied its synthetic process in detail.Fosinopril can be prepared through condensation by trans-4-cyclohexyl-L-proline(2) and[(R)-[(1S)-2-methyl-1-(1-oxopropoxy)-propoxy](4-phenylbutyl)phosphinyl]acetic acid(3).Compound 3 was obtained in an overall yield of 16.2%via condensation, debenzylation and resolution by using[hydroxy(4-phenylbutyl)phosphinyl]acetic acid (P1)as the starting material.Compound 2 was prepared in an overall yield of 12.2%via reduction amination,acylation,alkylation,esterification,sulfurization,desulfurization, catalytic hydrogenation by using L-glutamic acid as starting material.In this thesis, reactions for preparing compound 2 and 3 were studied and optimized,they were more suitable for industrial production.The intermediates were identified by MS,~1H NMR and their physical property.Tried to prepare fosinopril,but didn't get pure product.