SYNTHESIS OF A CHIRAL ALPHA-(AMINOOXY)ARYLACETIC ESTER .2. A ROUTE THROUGH A CHIRAL 2-HYDROXY-2-PHENYLACETIC ACID-DERIVATIVE

A simple and practical synthetic route has been developed for the synthesis of a chiral alpha-(aminooxy) ester (S)-16, which is a synthetic intemediate for a potent antipseudomonal cephalosporin antibiotic M-14659. In this synthetic route, the key intermediate is alpha-hydroxy acid (R)-7 (100%ee), which is prepared by an asymmetric reduction of alpha-keto ester with NaBH4-(R,R)-tartaric acid followed by a hydrolysis and an optical resolution using L-Leu-NHNH2. (S)-16 is obtained stereoselectively through 3 steps from (R)-7. HPLC analyses and NMR studies have proved that the (S)-16 thus prepared is completely optically pure.