A NEW APPROACH TO THE SYNTHESIS OF CILASTATIN, AN INHIBITOR OF RENAL DIPEPTIDASE

A convenient preparative synthesis of cilastatin, an inhibitor of rena l dipeptidase used in drugs with the antibiotic imipenem, has been ela borated. The key intermediate in this synthesis is 2-amino-7-chlorohep tanoic acid prepared by oxidative cleavage of cycloheptanone followed by bromination of 7-chloroheptanoyl chloride with subsequent amination of the 2-bromo-7-chloroheptanoic acid thus formed. All of the stages of the new synthesis are easily performed, as is the isolation of the intermediate products, and they do not require any organometallic reag ents.