Synthesis Of Antineoplastic Agent Of Nocodazole

ObjectiveResearch the best way to synthesis of antineoplastic agent ofnocodazole.The way with five steps and has advantages of high yield andeasy purification was chosen.A good method was adopted to develop thetarget compound.And their molecular structures(C1-C5) were confirmedby H-NMR and LCMS,and their purity were demonstrated by HPLC.MethodsFour synthesis routes were designed by antithetical disconnectionand synthesis.And the best way was chosen by compared with theothers.4-methoxybenzoic acid and thiophene were used as startingmaterial to give the (4-methoxyphenyl)(thiophen-2-yl)methanone byFriedel-Crafts reaction.The next compound (4-methoxy-3-nitrophenyl)(th-iophen-2-yl)methanone was given by nitrification and the electrophilicsubstitution component with acetic anhydride and nitric acid.Thecompound (3,4-diaminophenyl)(thiophen-2-yl)methanone was given byammoniation and reduction, the reducer was component with ferrouspowder and ammonium chloride.The target compound was got byring-closure reaction with (3,4-diaminophenyl)(thiophen-2-yl)methanoneand1,3-bis(methoxy-carbonyl)-S-methylisothiourea.The best reactionconditions which with high yield and easy to operate were build after research the effect of different molar ration or the time on the yield aswell as the effect of temperature.And their molecular structures wereconfirmed by H-NMR and LCMS,and their purity were demonstrated byHPLC.ResultsThe first build the best method to synthesis of nocodazole and eachof the intermediates. After optimize each of the intermediate’s yield hasbeen improved. And the total yield was53%.Second the syntheticeprocess was applicable in industrial preparation with highyield,simplified operate and on the safe.The last their molecularstructures were confirmed by H-NMR and LCMS,and their purity weredemonstrated by HPLC.ConclusionsThe target compound was given by five steps with Friedel-Craftsreaction, nitrification, ammoniation,reduction and ring-closure reaction.The synthetice process is applicable in industrial preparation with cheapmaterial, high yield,simplified operate and on the safe.