The Ace Inhibitor Perindopril Synthesis Process

The situation and nosogenesis of hypertension were described briefly in this paper. The action mechanism and development of antihypertensive drugs were also introduced, especially of the structure-activity relationships, pharmacokinetic properties and main side-effects of angiotensin converting enzyme inhibitors (ACEI).Perindopril, a non-thiohydroxy ACE inhibitor, launched in France in 1989, is used for the treatment of hyperpiesia and congestive heart failure with high activity, less side-effect and lower tolerance.Two routes, active ester and acyl chloride, were designed and researched in this paper on the basis of references from (S)-2,3-dihydro-1H-indole -2-carboxylic acid and N-[(S)-1-(ethoxycarbonyl)butyl]-(S)-alanine. The target compound, perindopril eburmine, was obtained through 5 steps in the first route and the overall yield, which was higher than that of another route through 4 steps, was 31.6%. The structure of perindopril eburmine was confirmed by the application of ¹H-NMR, ¹³C-NMR, MS and IR spectra.The key intermediate (2S,3aS,7aS)-octahydroindole-2-carboxylic acid(2) was synthesized via only one step, avoiding the steps of protection and deprotection of the carboxyl, with 7% higher yield than that of the references. The reaction conditions and purification method of perindopril eburmine were investigated emphatically.