1 research outputs found
Diastereoselective Hydrolysis of Branched Malonate Diesters by Porcine Liver Esterase: Synthesis of 5-Benzyl-Substituted C\u3csup\u3eα\u3c/sup\u3e-Methyl-ÎČ-proline and Catalytic Evaluation
Malonate diesters with highly branched side chains containing a preexisting chiral center were prepared from optically pure amino alcohols and subjected to asymmetric enzymatic hydrolysis by Porcine Liver Esterase (PLE). Recombinant PLE isoenzymes have been utilized in this work to synthesize diastereomerically enriched malonate halfâesters from enantiopure malonate diesters. The diastereomeric excess of the product halfâesters was further improved in the later steps of synthesis either by simple recrystallization or flash column chromatography. The diastereomerically enriched halfâester was transformed into a novel 5âsubstituted CαâmethylâÎČâproline analogue (3R,5S)â1c, in high optical purity employing a stereoselective cyclization methodology. This ÎČâproline analogue was tested for activity as a catalyst of the Mannich reaction. The ÎČâproline analogue derived from the hydrolysis reaction by the crude PLE appeared to catalyze the Mannich reaction between an αâimino ester and an aldehyde providing decent to good diastereoselectivities. However, the enantioselectivities in the reaction was low. The second diastereomer of the 5âbenzylâsubstituted CαâmethylâÎČâproline, (3S,5S)â1c was prepared by enzymatic hydrolysis using PLE isoenzyme 3 and tested for its catalytic activity in the Mannich reaction. Amino acid, (3S,5S)â1c catalyzed the Mannich reaction between isovaleraldehyde and an αâimino ester yielding the âantiâ selective product with an optical purity of 99â%ee