Biomimetric Synthesis Of Mannich Alkali, Tetrahydroisoquinoline And Tetrahydro-β-carboline

Enzomye acts important role in body, it can make the chemical reaction finished in mild physiological condition with high activity, high selectivity and high singularity and has the incomparable function with the usual chemical reaction. People have gradually cognized the function and mechanism of enzomye. So, in recent years, it is the hotspot about the research of coenzomye in biochemistry, esspecially in organic chemistry field.The tetrahydrofolate coenzyme is involved in the biochemical transfer of a one-carbon fragment at different oxidation levels. When the one-carbon unit is at the formaldehyde oxidation level, the imidazolidine with a five-membered ring structure is the active site. If benzimidazoline is used as tetrahydrofolate coenzyme model to react with nucleophilic reagent, the one-carbon unit at the formaldehyde and oxidation level will be transferred to the nucleophilic reagent, and the biomimetic synthesis to initiate the one-carbon unit transfer reaction of tetrahydrofolate coenzyme will be accomplished.Mannich alkali are an important organic compounds and have wide utility in the live especially in medical industry, dyeing industry. In this work, a convenient synthetic method for the preparation of Mannich alkali from carboxylic acids is provided with benzimidazoline used as tetrahydrofolate coenzyme model at formadehyde oxidation level. Thus the biomimetic synthesis of Mannich alkali was successfully accomplished by using benzimidazoline with alkaline amine as nucleophile reagents under the condition of acid. The novel synthetical method of 8 kind of Mannich alkali was finished including preserved configuration of Mannich alkali, this new sythetic method can be regarded as a covert Mannich reaction, it provides a important route to prepare Mannich alkali from carboxlic acid.1,2,3,4-Tetrahydroisoquinoline derivatives have prominent effects on cure the diseases of cardiopathy. So, the modification for the structures of 1,2,3, 4-tetrahydroisoquinone derivatives to find new drugs has been the emphasis of recent drug research. In this paper, we provided biomimetic synthetic methods for tetrahydroisoquinoline by using the benzimidazoline as a new tetrahydrofolate coenzyme model with 2-(3, 4-dimethoxyphenyl)ethylamine as nucleophile reagents under the condition of acid. Simultaneously we prepared benzimidazolines with two methods by the of reduction benzimidazolium salts with NaBH₄ and Grignard addition with benzimidazolium salts. Thus we provided a new biomimic synthetic method for 13 kind of tetrahydroisoquinoline starting from carboxylic aicd and halid, gave a new idea of the synthesis for new drugs.It can make many kind ofβ-carboline alkaloids which have bioactivity to antibacterium, antivirus and antitumor to start from 1,2,3,4-tetrahydro -β-carboline. So, it gets many attention of chemists to develop the methods for this kind of compounds. We provided biomimetic synthetic methods for tetrahydro-β-carboline by using the benzimidazoline as a new tetrahydrofolate coenzyme model with tryptamine as nucleophile reagents under the condition of acid. Simultaneously we prepared benzimidazolines with two methods by the reducton of benzimidazolium salts with NaBH₄ and Grignard addition with benzimidazolium salts. Thus we provided a new biomimic synthetic method for 9 kind of tetrahydro-β-carboline starting from carboxylic aicd and halid. A convenient synthetic method for preparing tetrahydro-β-carboline was provided.Benzimidazoline as a new tetrahydrofolate coenzyme model to perpare alkali can bring a byproduct N, N'-dimethylaniline, this byproduct can be recycled to produce benzimidazoline as raw materials. So, the model of benzimidazoline has predominance compared with other model in cost and environmental protection, meets the requirement of green organic chemistry.