PREPARATION OF OPTICALLY-ACTIVE SUCCINIC ACID-DERIVATIVES .1. OPTICALRESOLUTION OF -3-(CIS-HEXAHYDROISOINDOLIN-2-YLCARBONYL)PROPIONIC ACID

(+)-Monocalcium 3-(cis-hexahydroisindolin-2-ylcarbonyl)propionate] dih ydrate (KAD-1229, 1) is an optically active succinic acid calcium salt derivative with potent hypoglycemic effect, We investigated two optic al resolution methods, -3-(cis-hexahydroisoindolin-2-ylcarbonyl)propio nic acid 6 was esterified with (S)-N-benzyl mandelamide and the result ing diastereomeric esters were separated by column chromatography on s ilica gel to give 7 and 8 in 39.1% and 45.3% yields, respectively. The diastereomer 7 was hydrolyzed to give the optically active acid (-)-6 , The absolute configuration of(-)-6 was established as S by compariso n with an authentic sample, The alternative method was resolution usin g an optically active amine, Treatment of a solution of the racemic ac id 6 with 0.65eq of (R)-1-(1-naphthyl)ethylamine in ethanol gave the s alt in 23.2% yield with an optical purity of 96.8% ee.