Syntheses Of Xanthones Using 2,6-Dihydroxybenzoic Acid As Starting Material(Part ?) Re-optimization Of The Synthetic Process For Antineoplastic Drug Procarbazine(Part ?)

Objectives: In part I,to explore the synthetic route of xanthones in the purpose of finding a concise process with low pollution and high yields;In order to obtain more drug-like candidate for comprehensive treatment of diabetes.In part II,by choosing more affordable and readily available raw materials to synthesize procarbazine.Methods:(1)2,3,6-trihydroxy benzoic acid was prepared through nitration,reduction,diazotization,hydrolysis appling 2,6-dihydroxybenzoic acid as the raw materials.This compound reacted with phloroglucinol under the catalysis of Eaton's reagent leading to 1,3,5,8-tetrahydroxylxanthone and 1,3,7,8-tetrahydroxylxanthone.(2)Nitro-xanthone was obtained through the reaction of phloroglucinol with 5-nitro-2,6-dihydroxybenzoic acid,which was synthesized by nitration of 2,6-dihydroxybenzoic acid.Amino xanthones were synthesized by the reduction of nitro-xanthone compounds.(3)Haloxanthones were prepared through the reaction phloroglucinol with 5-halo-2,6-dihydroxybenzoic acid,which was synthesized by halogenation of 2,6-dihydroxybenzoic acid.(4)The ultimate product procarbazine and its intermediate products B-1,B-2 B-3 and B-4 were synthesized with p-toluic acid as starting material through four-steps reactions.Results:(1)Eleven intermediate compound with nine xanthone compound were obtained,where six new compounds ? All the prepared compounds were characterized by NMR and the ESI-MS.(2)Introduction of electron-withdrawl substituents to 2,6-dihydroxybenzoic acid enhances its reactivity with phloroglucinol resulted in greater yield.(3)The target compound procarbazine and three intermediates were synthesized use raw material p-Toluic acid,and all the compounds were identified by NMR and ESI-MS.Conclusion: In part I,introduction of electron withdrawing groups 2,6-dihydroxybenzoic acid enhances its reactivity with phloroglucinol resulted in greater yield.This is a preferred method for preparing xanthone derivatives.In part II,a series of intermediates and target ptoducts procarbazine were synthesized using p-toluic acid as the raw materails in accordance with the optimized processes.Effectively reduce environmental pollution and raw material consumption.