A new method for the synthesis of fatty acid amides

Abstract

The amide bond is an essential part of many natural products and is also found in a lot of today’s pharmaceuticals. The fatty acid amides are a group of natural products that has shown biological activity towards several receptors in both the peripheral and the central nervous system. The traditional methods for the formation of amide bonds tend to give low to moderate yields when utilized on long chain fatty acids, and so, an effective and reliable method for the synthesis of these interesting compounds seems to be in demand. In this thesis, a method using N,N’-carbonyldiimidazole (CDI) as coupling reagent in the preparation of fatty acid amides is tested. A total of 20 fatty acid amides have been prepared, within the groups N-acyldopamines, N-acylamino phenols, N-acylamino acids, and primary fatty acid amides. Among these, the N-acylamino acids gave the best results, with yields over 80 %. The primary fatty acid amides were made in low yields with saturated fatty acids, but quantitative yields with the polyunsaturated fatty acids. Both the N-acyldopamines and the N-acylamino phenols were prepared in moderate yields. A synthesis path towards an analogue of ω-3 DPA using DHA as starting material, was also followed. The first 8 steps were conducted; in a total yield of 7 %. The final two steps remain to be done. Several of the reactions were not optimized, and improvements of the yields should be possible.

Amidbindingen er en essensiell del av mange naturstoffer, og er også å finne i mange av de legemidler som benyttes i dag. Fettsyreamider er en gruppe naturstoffer som har vist biologisk aktivitet mot flere reseptorer i både det perifere og det sentrale nervesystemet. Tradisjonelle metoder for dannelse av amidbindinger gir ofte lavt til moderat utbytte når de benyttes med lange fettsyrekjeder. Dermed virker det å være et behov for effektive og pålitelige metoder for syntese av disse interessante forbindelsene. I denne oppgaven blir en metode der N,N’-karbonyldiimidazol (CDI) anvendes som koblingsreagens i tillagingen av fettsyreamider utprøvd.