Synthesis Of Biaryl Bromides Catalyzed By Vanadium-dependent Chloroperoxidas

The total synthetic chemical method for synthesizing halogenated compounds involves too many toxic halides,and its application was limited.Vanadium-dependent chloropheroxidases(VCPO)was a kind of biological enzyme catalyst with high catalytic activity and wide sources,which has an important application prospect in the field of biological enzyme catalysis In the aticle,the bromine substitution reaction of biphenyl compounds and the synthesis of biphenyl seven-membered lactone compounds catalyzed by Ci VCPO were studied.In the first part of this aticle,the bromine substitution of biaryl phenol catalyzed by enzyme was studied,and a series of macrocyclic biphenyl bromides were obtained by one-pot and two-step coupling reaction cascade with Suzuki.Through the general investigation of biological enzyme method,the conditions of reaction buffer p H,hydrogen peroxide and potassium bromide concentration,enzyme concentration and so on were optimized,and the best reaction conditions were obtained.The results show that the reaction can be successfully carried out,but the yield of tribromo-substituted products is low because of the position selectivity of benzene ring bromine substitution.Then the substrate spectrum was studied,and 15 racemic chiral compounds were obtained by semi-preparation scale reaction.The chemical enzymatic cascade coupled with Suzuki was also explored,which proved the possibility of this method.Finally,the structures of all products were confirmed by ~1H NMR and 13 C NMR spectra,and the absolute configuration of products was determined by single crystal diffraction.As a result,a new method of synthesizing bromine-axis chiral compounds with high catalytic efficiency catalyzed by biological enzymes under mild conditions was developed.In the second part of the aticle,the enzymatic synthesis of benzoheptalactone from biphenylene acid compounds was studied.Similarly,the optimal reaction conditions were obtained by screening the enzyme concentration and the p H of buffer solution through the control experiment,which proved that the biological enzyme could be used to synthesize lactone compounds.Finally,the substrate spectrum was studied,and the reaction was expanded to a semi-preparation scale,and six kinds of benzoheptalactone compounds were isolated.All the product structures were confirmed by 1H NMR and13 C NMR spectra.On the whole,the research on the enzyme catalysis of Ci VCPO shows that the synthesis catalyzed by greener,milder and more efficient biological enzyme has certain advantages and significance compared with the traditional chemical synthesis,and it is of reference significance to verify and broaden the enzyme-catalyzed synthesis of pharmaceutical intermediates.