USE OF IMMOBILIZED LIPASE IN SYNTHESIS OF METRONIDAZOLE DERIVATIVES

GARRIDO, JUAN M.; GALVEZ, CAROLINA ELIZABETH DEL VALLE; MURO, ANA CAROLINA; LOANDOS, MARÍA DEL H.; VILLECCO, MARGARITA B.

Jornada; XXXIX Jornadas Científicas Asociación de Biología de Tucumán; 2022

Use of enzymes in the pharmaceutical industry has increased for several reasons, among them, we can highlight their excellent selectivity,significant reduction in the use of reagents and solvents, and the possibility of obtaining products that are not easily synthesized by classicalchemical methods. Immobilized Candida antarctica lipase (CALB, Novozym 435®) exhibits great stability and capacity for esterificationand transesterification reactions in non-aqueous media. In this work, esterification of metronidazole (MTZ) with octanoic and nonanoicacids (C8 and C9) was carried out using CALB in order to obtain active ester derivatives of metronidazole. The octanoic and nonanoic acidesters were obtained with metronidazole in hexane, CALB, and the respective acid. The mixture was stirred at 300 rpm and 50°C. Theprogress of the reaction was monitored by TLC, while the isolation, identification and purity of the reaction products was performed byCC, GC-MS, and NMR using 1D and 2D experiments (COSY, HSQC, and HMBC). We obtained the octanoic and nonanoic esters of MTZwith yields between 85% and 93%. In both compounds, the mass spectra showed the molecular ion and a base peak at m/z 126corresponding to the loss of entire side chain. The use of enzymes in synthesis of pharmacologically active derivatives is fully justified dueto the ease isolation of products, the absence of toxic reagents and the lower costs derived from enzyme recovery