Development of the method for the preparation of amides using enzyme and coupling reagent

Abstract

Mnoštvo prirodnih organskih spojeva, kao i sintetiziranih biološki aktivnih spojeva, u svojoj strukturi sadrži amidnu vezu. Unatoč velikom broju metoda koje se koriste u pripravi amidne veze, i dalje postoji potreba za razvojem novih metoda. U sklopu ovog diplomskog rada istraživana je jedna od metoda priprave amidne veze reakcijom estera i amina koja obuhvaća primjenu enzima i kondenzacijskog reagensa kao katalizatora. Reakcije amina i estera prvo su provedene u klasičnim bazno kataliziranim uvjetima, a zatim u prisutnosti enzima Candida antarctica lipaza B (CalB) kao katalizatora u bezvodnom organskom otapalu. Iste enzimski katalizirane reakcije provedene su i uz dodatak benzotriazol-1- iloksitris(dimetilamino)fosfonijevog heksafluorofosfata (BOP) kao kondenzacijskog reagensa. Uvjeti reakcija provedenih CalB-BOP metodom optimirani su u cilju dobivanja što boljih iskorištenja. Usporedbom dobivenih rezultata na ispitanim esterima i aminima utvrđene su prednosti i nedostatci CalB-BOP metode, te je utvrđen potencijal ove metode u odnosu na reakcije provedene u klasičnim bazno kataliziranim uvjetima i enzimski katalizirane reakcije.A lot of natural organic compounds and synthetic biologically active compounds contains amide bond. Despite a large number of methods used for the preparation of amides, there is still a need for development of new methods. The aim of this diploma thesis is the study of the method for preparation of amides which includes the application of enzyme and coupling reagent as catalysts in the reaction between ester and amine. The reactions of amines and esters were first carried out in terms of the classical base catalysed method, and then in terms of enzyme catalysed method (Candida antarctica lipase B (CalB) in organic solvent, anhydrous reaction conditions). The same reactions have been conducted with enzyme CalB and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) as coupling reagent. Reaction condition of CalB-BOP reactions were optimised in order to obtain the best possible efficiency. Advantages and disadvantages as well as the potential of the CalB-BOP method were determined by comparing obtained results of conducted base catalyse, enzyme catalysed and CalB-BOP catalysed reactions