Synthesis of enantiostructured triacylglycerol possessing caprylic acid, DHA and naproxen

Abstract

The project was composed of a six step synthesis of enantiostructured triacylglycerols possessing a medium chain saturated fatty acid (8 carbon caprylic acid), an n-3 polyunsaturated fatty acid (docosahexaenoic acid, DHA) and an active drug. The main original part of the project was the coupling of an active drug on triglyceride and three drugs tested were: Aspirin, (±)-Ibuprofen and (S)-Naproxen. The coupling with Aspirin didn't work because there were two active sites on the compound that the catalyst could choose from, but the other two drugs gave good results. Some difficulties were experienced with the second last step, when the benzyl protecting group was removed. Acyl migration was observed, but a procedure was developed to avoid such migration. The identity of all compounds was established and they were fully characterized by 1H and 13C NMR and IR spectroscopy and accurate mass spectrometry analysis. All chiral compounds were measured for optical activity.

Verkefnið fól í sér sex skrefa efnasmíð til að mynda handhverft stöðubundið þríglýseríð skipuðu miðlungslangri mettaðari fitusýru (8 kolefna kaprýl sýra), ómega-3 fjölómettaðri fitusýru (dókósahexaen sýra, DHA) og virku lyfi. Helsta nýjung verkefnisins var að kúpla inn virku lyfi á þríglýseríð og voru þrjú lyf prófuð: Aspirín, (±)-Ibúprófen og (S)-Naproxen. Ekki gekk að kúpla inn Aspiríni vegna þess að hvatinn gat valið um tvo staði til árásar en hin lyfin tvö gáfu góðar niðurstöður. Smá erfiðleikar komu upp við næst seinasta skrefið, þegar reynt var að fjarlægja benzyl verndarhópinn. Þá varð asýl umröðun en þróuð var leið til þess að komast hjá slíkri umröðun. Bygging allra efna var að fullu sannkennd með 1H og 13C NMR og IR litrófsgreiningu og nákvæmum massamælingum. Ljósvirkni allra hendinna efna var mæld.