Synthesis of (3S, 4S)- and (3S, 4R)-4-Amino-3-hydroxy-6-methylheptanoic Acid, and Their N-(Acetyl- l -valyl- l -valyl) Derivatives

Natural (−)(3S,4S)-4-amino-3-hydroxy-6-inethylheptanoic acid (10a) present in pepstatins, specific inhibitors of acid proteases, and its (+) (3S,4R) diastereomer (10b) were synthesized starting from 3-deoxy-1,2-O-isopropylidene-α-d-erythro-pentodialdo-1,4-furanose (1) through highly stereoselective and stereospecific routes. The partial pep tide of pepstatin Ac, N-(acetyl-l-valyl-l-valyl)-(3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid (15a) and its (3S,4R) diastereomer (15b) were synthesized via azide-coupling of the t-butyl esters of 10a and 10b with acetyl-l-valyl-l-valine azide, respectively. Compound 15a inhibited proteolysis by pepsin, however, the diastereomer 15b showed no inhibition against pepsin.