Fosinopril synthesis

Another example using a prochiral acetate and asymmetric hydrolysis was described by the Bristol-Myers Squibb group for an intermediate in the synthesis of Monopril (fosinopril sodium) (41), an ACE inhibitor (Scheme 19.23). The prochiral substrate 42 was hydrolyzed both when R = phenyl or cyclohexyl to the corresponding (S)-(-)-monoacetate 43. The reaction was carried out in a 10% toluene biphasic system with either PPL or Chromobacterium viscosum lipase. The cyclohexyl monoacetate was obtained in 90% yield with an optical purity of 99.8%.107 195... 

One synthesis of fosinopril, a drug used to combat high blood pressure, starts with the reduction of (5)-pyroglutamic acid to the primary alcohol, followed by protection of the OH and NH groups. 

In view of reusabiUty of the catalyst and easy separation/purification of the products, the new procedure is advantageous in practical applications, e.g., the synthesis of fosinopril sodium (Scheme 21). 

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