Hydrolysis of new phthalimide-derived esters catalyzed by immobilized lipase.
The last step of the production of four phthalimide-derived acids, designed to act as antiasthma drugs, was performed by enzymatic hydrolysis of the respective methyl or ethyl esters. The esters 4-ethyl-[2-(1,3-dioxo-1,3-dihydro- 2-isoindoylyl)]-phenoxyacetic methyl ester (PHT-MET), 4-ethyl-[2- (1,3-dioxo-1,3-dihydro-2-isoindoylyl)]-phenoxyacetic ethyl ester, 4-(1, 3-dioxo-1,3-dihydro-2-isoindoylyl)-phenoxyacetic ethyl ester, and 2-(1,3-dioxo-1, 3-dihydro-2-isoindoylyl)-phenoxyacetic ethyl ester were hydrolyzed by immobilized lipase. The enzymatic reaction could be used only to produce the desired 4-substituted compounds. The best result that was found to hydrolysis of PHT-MET, and, therefore, that ester was selected for optimization experiments in a three-phase system. Reactions were performed with solid biocatalyst (Lipozyme RM IM), organic solvent phase (ethyl acetate), and aqueous phase (saturated Na2CO3 solution). To optimize the reaction conditions, an experimental design optimization procedure was used. The variables studied were the amount of enzyme, the temperature, and the volume of the aqueous solution. Time course experiments were then performed for different initial enzyme concentrations (0.5, 0.9, and 1.4 UH/mL of solvent). The optimized reaction conditions found were 20 mg of Lipozyme (0.9 UH/mL solvent) and 5.0 mL of Na2CO3(sat) at 40 degrees C for 6 h.
Bevilaqua
Juliana Vaz
JV
Programa de Engenharia Química/COPPE, Universidade Federal do Rio de Janeiro, Centro de Tecnologia (CT), Lab. 549-2 and 536-B, Cidade Universitária, Ilha do Fundáo, CEP 21945-970, Rio de Janeiro, Brazil.
Lima
Lidia M
LM
Cunha
Aline Gomes
AG
Barreiro
Eliezer J
EJ
Alves
Tito L M
TL
Paiva
Lucia Moreira Campos
LM
Freire
Denise M Guimarães
DM
D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis*; D004789:Enzyme Activation; D004800:Enzymes, Immobilized / Q000737:chemistry; D004952:Esters; D005240:Feasibility Studies; D006868:Hydrolysis; D007536:Isomerism; D008049:Lipase / Q000737:chemistry*; D010797:Phthalimides / Q000737:chemistry*; D013696:Temperature; D014867:Water / Q000737:chemistry
D018927:Anti-Asthmatic Agents; D004800:Enzymes, Immobilized; D004952:Esters; D010797:Phthalimides; D014867:Water; C093666:Lipozyme; D008049:Lipase