Study On The Synthesis Of D-tryptophan And The Intermediate Of Resveratrol:3,5-Dihydroxyacetophenone

This dissertation briefly introduced two natural products:D-tryptophan and resveratrol, including their applications and potential uses. We did some research on the synthesis of D-tryptophan and3,5-Dihydroxyacetophenone which was the key intermediate of resveratrol.D-tryptophan and its derivatives are important pharmaceutical intermediates with anti-drug-resistance and lower rate of causing hypersensitivity. They can be used as non-nutritive sweeteners and food preservative, so D-tryptophan is considered as an important kind of non-protein amino acid. DL-tryptophan was obtained using gramine as the primary material via condensation and hydrolysis. Resolution was carried out by using D-tartaric acid as resolving agent, and benzaldehyde as catalyst to cause the asymmetric transformation from L-tryptophan to D-tryptophan, then the obtained D-tryptophan D-tartaric acid salt was neutralized with triethylamine to give D-tryptophan with the yield of52.6%which was higher than the theoretical yield of conventional methods. The effects of various reaction parameters on condensation and resolution were studied in detail and optimal conditions were as follows. The condensation was carried out using toluene as solvent at reflux, the molar ratio of sodium methoxide and gramine was0.2:1.0and that of gramine and diethyl acetamidomalonate was1.0:1.2. The resolution was carried out using acetic acid as solvent at70℃, the molar ratio of benzaldehyde and DL-tryptophan was0.1:1.0and that of DL-tryptophan and D-tartaric acid was1.0:2.0.Resveratrol is a new natural anti-cancer drug and can be used to cure cardiovascular diseases, and the synthesis of3,5-Dihydroxyacetophenone which was the key intermediate was studied. A totally new synthetic method was designed by using3,5-Dihydroxybenzoic acid as starting material via a series of reactions including esterification, benzyl protection, hydrolysis, acid chlorization. nucleophilic substitution, hydrolytic decarboxylation and deprotection.The total yield was76.7%. The effects of various reaction parameters on benzyl protection and nucleophilic substitution reaction were studied in detail and optimal conditions were obtained. The benzyl protection reaction was carried out using acetone as solvent, Nal as catalyst and K2CO3as deacid reagent under reflux, the molar ratio of benzyl chloride and ethyl3,5-dihydroxybenzoate was2.3:1.0and that of K2CO3and ethyl3,5-dihydroxybenzoate was2.5:1.0. The nucleophilic substitution reaction was carried out using acetonitrile as solvent, a stoichiometric amount of MgCl2·6H2O as chelation reagent, triethylamine as deacid reagent at room temperature for12hours, the molar ratio of diethyl malonate and3,5-dibenzyloxy chloride was1.0:1.0and that of triethylamine and3,5-dibenzyloxy chloride was2.0:1.0.The structures of some important intermediates and products were comfirmed by HNMR, IR and MS.