Synthesis And Study On Three Kinds Of New Tetrahydrofolate Coenzymes Model Compounds

In the reactions of living body, enzymes play important role. Compared to the common organic reactions, the reactions in living body are usually perfect related to the reaction rate and selectivity. The function of thtrahydrofolate (THF) coenzymes in living body is transferring one carbon unit for biosynthesis and metabolism, and almost all methylated reactions in living body are finished by thtrahydrofolate coenzymes. To date, the structure and function of THF coenzyme has been perfectly defined and the active center is thought to be the unsymmetric imidazoline ring. Stimulated by the important role of THF coenzyme in living body, in this paper we designed and synthesized a series of THF coenzyme models and reported some important reactions of the models, such as hydrolysis, reduction, addition and one carbon units transfer et. al. at the oxidation levels of formaldehyde and formic acid. Especially, we also reported two types of important reactions of THF coenzyme models—exchange reaction with aromatic aldehydes and hydride transfer reaction. The main contents in this paper have been summarized as followings:Part 1In order to probe the reactivity of THF coenzyme models, some 3aryl-substituted imidazolium iodides as THF coenzyme models, such as 1,2-Dimethyl-3-(4-methoxyphenyl)-4,5-dihydro-3H-imidazolium iodide, 1,2-Dimethy l-3-(4-nitrophenyl)-4,5-dihydro-3H-imidazolium iodide, 1,2-Dimethyl-3-(2-nitrophen yl)-4,5-dihydro-3H-imidazolium iodide and l,2-Dimethyl-3-(2,4-dinitrophenyl)-4,5-dihydro-3H-imidazolium iodide, were synthesized and applied to the hydrolysis reaction. We found that the model compounds can be easily hydrolyzed in the dilute sodium hydroxide solution and to form a series of N-methyl-N-acetyl-N'-aryl ethylene diamine derivatives, pharmaceutically important intermediates. This process efficiently imitated hydrolysis mechanism of tetrahydrofolate coenzymes. Moreover, we found that these models can be easily reduced to imidazolidines. Based on the above works, we obtained some important understanding on the structural andelectronic factors of these models.We were interested in the synthesis of the derivatives of dihydroimidazolium iodides or imidazolidines during our investigation on tetrahydrofolate coenzyme models. In order to test the efficiency of this type of model, we need synthesize a series of C-2 aryl-substituted imidazolidines. Obviously, this work is difficult, mainly because, to each of this type of compound, we have to repeat the process according to the method described previously. For such reason, we hope to exploit a new and convenient method to prepare C-2 aryl-substituted imidazolidines. In this paper, we reported a convenient method to prepare a series of C-2 aryl-substituted imidazolidines through the simple diamine transfer reactions between C-2 alkyl-substituted imidazolidines and aromatic aldehydes under the catalysis of n-butylamine.On the study of the reaction of l-3-(4-nitrophenyl)-4,5-dihydro-3H-imidazolidine with 3,4-dimethoxyphenethylamine, unexpectedly, we obtained two new compounds, 1:2 addition product and a N-methyl-N-ethyl-N-arylethylenediamine. The result suggests that substituted imidazolidine can be used as novel hydride transfer reagent. Hydride transfer reaction is very important in living body, and NADH and NADPH have long been known to act as coenzymes in biological redox reactions. It was established that in the reduced form of the coenzyme the active part is 1,4-dihydropyridine. In this paper, to the best of our knowledge, we firstly reported this result. Subsequently, by using the reagent, we successively reduce some aromatic aldehydes to corresponding alcohol.Part 2In the previous works, we systemly studied the effect of structure and electron on our models. On this basis, we designed and synthesized a more active model, l-Tosyl-3,4-dimethyl imidazolium iodide. The model compound can react with some carbon nucleophiles, such as: malononitrile, nitromethane, acetylacetic ester, acetylacetone, benzyl acetone and ethyl malonate, and form some partly transfer compound, ring-opened compounds and ring-locked compounds. The model...