Synthesis Of Oleoylethanolamide And Taurine Analogues

N-Oleoylethanolamide(OEA),a high-affinity endogenous ligand of PPAR-a,is expected to become new anti-obesity drug for its safety,high efficiency and low side effects.Most of the OEA synthetic methods in the literature are uneconomical,require harsh condition,chromatographic separation,or time consuming process,generate excess amount of waste.Herein,a green,mild and efficient synthetic method of OEA was developed.The reaction conditions were optimized as follows:the mole ratio of ethyl oleate and ethanolamine is 1:7.5,the amount of sodium methoxide is 6%of the mass of ethyl oleate,the reaction temperature is room temperature,and the reaction time is 2 hours.The crude product was recrystallized from ethyl acetate to obtain OEA in 81.7%yield with 91.36%purity.The raw material ethyl oleate used in the synthesis of OEA is derived from natural oils and fats of both animals and vegetables.As a consequence,the raw material contains a series of other fatty acid ethyl esters with different carbon number and saturation state,making it difficult to prepare high-purity OEA.In this thesis,the commercially available ethyl oleate was purified twice by urea adduction before its application in OEA synthesis.The purification process conditions were optimized as follows:absolute ethanol is used as solvent.In the first urea adduction,the mass ratio of urea to crude ethyl oleate is 0.6,the mass ratio of absolute ethanol to crude ethyl oleate is 6,and the crystallization temperature is 20℃.In the second urea adduction,the mass ratio of urea to crude ethyl oleate is 2.6,the mass ratio of absolute ethanol to crude ethyl oleate is 12,and the crystallization temperature is 20℃.After twice urea adduction purification,the purity of ethyl oleate increased from 80.74%to 90.56%,and the recovery rate was 72.24%.Hypotaurine,thiotaurine,and S-(2-aminoethyl)thiosulfate belong to taurine analogues because of their structure similarity.They all have antioxidant effect and a variety of biological functions.They can be metabolized into non-toxic taurine in the human body,and have broad application prospects in food preservation,skin care and sperm preservation in vitro.However,the synthetic methods of hypotaurine reported in the literature used a long synthetic route offered poor product quality and low yield.In this thesis,the synthesis route of hypotaurine is shortened from 5 steps to 3 steps,which is more suitable for industrial production.Moreover,thiotaurine was synthesized from hypotaurine,and S-(2-aminoethyl)thiosulfuric acid was synthesized from 2-chloroethylamine hydrochloride.Both synthesis methods are mild with high yield and suitable for industrial production.