Synthesis And Penetration Enhancing Activity Of Tryptophan Ester Hydrochloride

Tryptophan ester hydrochloride,as a derivative of natural product amino acid,has the advantages of safety and biodegradability.It is widely used in medicine,agriculture,chemical industry,food,materials and cosmetics industry.Tryptophan ester hydrochloride is commonly synthesized by sulfoxide chloride,hydrogen chloride,p-toluene sulfonic acid and so on.Although new research has been reported in the catalysts of esterification,large-scale production can not be achieved due to their limitations.P-toluene sulfonyl chloride as esterification catalyst has the advantages of high activity,short reaction time and high yield.Therefore,p-toluene sulfonyl chloride as a catalyst has broad prospects.The research of this topic is mainly divided into the following sections:Part ?: In this paper,the target product was synthesized by p-toluene sulfonyl chloride(PTSC)and methanol system.Tryptophan was added to p-toluene sulfonyl chloride and methanol system.Neutralization and esterification were used to synthesize tryptophan ester hydrochloride in one pot.Compared with the method of p-toluene sulfonyl sulfonic acid,p-toluene sulfonyl chloride was added at one time,and tryptophan ester hydrochloride was synthesized directly.Complex post-processing process is eliminated and process flow is reduced.;the amino acid of the reaction raw material does not need amino protection group,and the purity of the purified product is over 90%.The structure of the target product can be highly consistent with reactant,so the target products with different configurations can be selectively synthesized.Part ?: Tryptophan methyl ester hydrochloride was successfully synthesized by p-toluene sulfonyl chloride(PTSC).The process of tryptophan methyl ester hydrochloride was optimized.According to the single factor experiment,three factors,including reaction time,reaction temperature and molar ratio of reactants,were selected.On the basis of single factor experiment,three factors and three levels were investigated by response surface method.Quadratic polynomial regression equation between yield of tryptophan methyl ester hydrochloride and reaction temperature,reaction time and material ratio was established.The experimental results show that factors A(molar ratio of reactants),B(reaction temperature),C(reaction time)and interaction terms AB,BC,AC all have significant effects on the yield.The significant influence of various factors on the yield of the target product was as follows: reaction temperature >material ratio > reaction time.The optimum reaction conditions were determined by response surface methodology: reaction temperature 69.39 ?,reaction time 14 h,n(L-tryptophan): n(PTSC)0.48:1.0.Under these conditions,the yield of the target product was 84.55%,which is close to the predicted value(85.72%).It shows that the model has a good fitting degree and can significantly fit the effects of reaction time,reaction temperature and material ratio on the yield of the target product.Part ?: The effects of tryptophan methyl ester hydrochloride with different configuration on transdermal permeation were investigated by using isolated suckling pig skin as biofilm,acyclovir and caffeine as drug models and synthesized tryptophan methyl ester hydrochloride(a)as promoter.The results showed that L-tryptophan methyl ester hydrochloride had a better effect on the transdermal penetration of acyclovir,while D-tryptophan methyl ester hydrochloride had a better effect on the transdermal penetration of caffeine,which indicated that different configuration of tryptophan methyl ester hydrochloride had different effects on the penetration of different drugs.At the same time,acyclovir was used as a drug model to study the effect of L-tryptophan methyl ester hydrochloride alone and in combination with menthol(b).The solution of 0.3%a,0.6%a,1.0%a and 0.3%a + 1.0% b,0.6%a + 1.0% b,1.0%a + 1.0% b were used as the test solution,and the physiological saline was used as the acceptor to test the permeation enhancing activity.Tryptophan methyl ester hydrochloride could significantly promote the percutaneous absorption of acyclovir either alone or in combination with menthol.When the content of tryptophan methyl ester hydrochloride is 0.6%,the effect is the best whether it is used alone or combined with menthol.