RESUMEN
A facile control of the acylation position at the primary hydroxyl and amino of acyclovir, respectively, was achieved and five polymerizable acyclovir prodrugs were synthesized. Various reaction conditions were studied in detail. Thus, lipase acrylic resin from Candida antarctica (CAL-B) in pyridine or acetone showed high chemo-selectivity toward the primary hydroxyl of acyclovir. However, lipase PS 'Amano' (PS) in DMSO selectively acylated the amino group. The selectivity of PS could be adjusted by changing reaction solvents. The acyclovir vinyl derivatives obtained would be important monomers used for the preparation of macromolecular nucleoside drugs.
Asunto(s)
Aciclovir/síntesis química , Amidas/síntesis química , Ésteres/síntesis química , Lipasa/química , Polímeros/síntesis química , Profármacos/síntesis química , Aciclovir/química , Acilación , Antivirales/síntesis química , Hongos/enzimología , Compuestos Orgánicos/química , Profármacos/química , Solventes/químicaRESUMEN
Hydrolase-catalyzed Michael addition of imidazole derivatives to acrylic monomers in organic medium was described. A serial of N-substituted imidazole derivatives were successfully synthesized in moderate yields by the catalysis of hydrolases in organic medium. Nine commercially available hydrolases from different sources were screened and all of them were found to be able to catalyze this type of addition reaction. The reaction yields depended on the solvent properties and the solvents with higher log P value supported this enzyme-catalyzed reaction to give higher conversion. Influence of the structure of the Michael acceptor and donor on the enzymatic Michael addition was also investigated. The acceptor with shorter alcohol chain afforded a higher yield. A more rapid conversion was observed when the donor had an electron-withdrawing group. This hydrolase-catalyzed Michael addition reaction has widened the applicability of biocatalysts in organic and bioorganic synthesis.
Asunto(s)
Acrilatos/química , Hidrolasas/química , Imidazoles/química , Compuestos Orgánicos/química , Aspergillus oryzae/enzimología , Bacillus subtilis/enzimología , Proteínas Bacterianas/metabolismo , Catálisis , Cromatografía Líquida de Alta Presión , Endopeptidasas/metabolismo , Hidrolasas/síntesis química , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Solventes , Temperatura , Factores de TiempoRESUMEN
A series of vinyl drug esters was synthesized using acyclovir and chloramphenicol with different carbon chain length acyl donors by alkaline protease from Bacillus subtilis and Lipozyme respectively, in non-aqueous medium. The corresponding vinyl drug derivatives were confirmed by nuclear magnetic resonance and infrared spectrometry. The influences of different organic solvents, reaction time, temperature, and content of water on synthesis of vinyl chloramphenicol esters were studied.