LIPASE-CATALYZED SYNTHESIS OF CHIRAL AMIDES - A SYSTEMATIC STUDY OF THE VARIABLES THAT CONTROL THE SYNTHESIS

A systematic study of the aminolysis of esters catalyzed by different lipases From different origins was carried out. A factorial analysis s howed that the main variables that control the amide synthesis are: te mperature, hydrophobicity of the solvent, reaction volume and amount o f water added to the reactor medium. Besides, several undescribed inte ractions of variables are significative in the control of the process, too. The resolution of racemic esters or amines was analyzed. Lipases from Rhizopus niveus,Candida antarctica B and PPL gave the best enant ioselectivities in the resolution of chiral esters while C.rugosa and P.cepacia lipases were the less interesting lipases. alpha-Chymotrypsi n shows lower enantioselectivity and yield than Rhizopus niveus, C. an tarctica B and PPL lipases in the resolution of racemic esters. This p rotease needs a large excess of acyl donor in respect to the amine and works at a lower temperature than lipases due to its low thermostabil ity. All the tested lipases showed R-enantiopreference in the aminolys is of esters using (R,S) 1-phenyl-ethylamine. In this reaction, the li pase A from C. antarctica, (SP526) and Rhizopus niveus lipase are good catalysts for the synthesis. On the other, PS and PPL are less intere sting biocatalysts. Therefore, the optimum biocatalyst is different if we want to resolve (R,S) esters or (R,S) amines. The aminolysis is in teresting for the resolution of racemic amines but not for the resolut ion of racemic esters. The immobilization does not alter the enantiopr eference of the lipases. (C) 1998 Published by Elsevier Science Ltd. A ll rights reserved.