Synthesis And Characteristic Of A Dipeptide Sweetener With 40,000 Times Sweeter Than Sucrose

N-[N-[3-(3-Hydroxy-4-methoxyphenyl)propyl]-L-?-aspartyl]-S-tert-butyl-L-cysteine-1-meth yl ester,a dipeptide compound with approximately 40,000 times sweeter than sucrose,was synthesized by aspartic acid,cysteine,3-hydroxy-4-methoxyphenylpropanal.First of all,Isovanillin,Guaiacol,5-Bromo-2-methoxyphenol,3-Hydroxy-4-phenylacetic acid,Eugenol were assumed to select the best scheme to prepare 3-hydroxy-4-methoxyph enylpropanal,with a series of classical organic reactions,Aldol reaction,Friedel-Crafts al kylation,Lemieux-Von Rudloff oxidation,Mitsunobu reaction,Wittig reaction,etc.After c ontinous explorations,3-hydroxy-4-methoxyphenylpropanal was perfectly obtained through Wittig reaction,Hydrogenation reduction,DIBAL-H reduction(diisobutylaluminium hydrid e)with starting material isovanillin.Afterwards,S-tert-butyl-L-cysteine-1-methyl ester was firstly prepared by dissolving Stert-butyl-L-cysteine in methanol and dichlorosulfoxide.Then,it was coupled with N-(tertbutoxycarbonyl)-L-?-aspartic acid-4-tert-butyl ester via 1-(3-dimethylaminopropyl)-3-ethylca rbodiimide hydrochloride(EDCI)and 1-hydroxybenzotriazole(HOBt)to produce N-(N-tertbutoxycarbonyl-4-tert-butyl ester-L-?-aspartyl)-S-tert-butyl-L-cysteine-1-methyl ester.Last,th e dipeptide,namely N-(L-?-aspartyl)-S-tert-butyl-L-cysteine-1-methyl ester,was obtained by dissolving it in the hydrochloric acid-dioxane.At last,3-(3-Hydroxy-4-methoxyphenyl)propanal reacted with N-(L-?-aspartyl)-S-tert-bu tyl-L-cysteine-1-methyl ester to obtain an intermediate Schiffe Base in 60% methanol-wate r mixture,further catalyzed by 10% Pd/C in hydrogenation atmosphere under room temp erature and ambient pressure to synthesis N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-?-aspartyl]-S-tert-butyl-L-cysteine-1-methyl ester.The structure of the final product was iden tified by Infrared Spectroscopy,Mass Spectrometry and Nuclear Magnetic Resonance.