Synthesis of D‐ and L‐5‐Oxaproline and of a New Captopril Analogue

The 1,3‐dipolar cycloaddition of the C ‐ t ‐butyloxycarbonyl‐ N ‐mannosyl‐nitrone 5 , formed in situ from the partially protected D ‐mannose‐oxime 3 and the glyoxylate 4 , to ethylene gave preferentially the (3 S )‐ N ‐glycosyl‐isoxazolidine 6 which was transformed into the 3‐isoxazolidine‐carboxylate ( L ‐5‐oxaproline ester) 12 and into some derivatives thereof. The ( S )‐configuration of 12 was proved by chemical correlation with a derivative of L ‐asparagine. The D ‐5‐oxaproline ester was obtained from the corresponding N ‐ribosyl‐nitrone 24 . Two protected dipeptides containing either C ‐terminal‐ ( 28 ) or N ‐terminal‐5‐oxaproline (= Opro) ( 30 ) were synthesized. Starting from 12 , the analogue 1 of captopril® ( 2 ) was prepared and its activity as an inhibitor of the angiotensin‐converting‐enzyme (ACE) was examined.