Preparation method for chiral pentabasic bicyclic guanidine based on aziridine

Abstract

The invention discloses a preparation method for chiral pentabasic bicyclic guanidine based on aziridine. The method comprises the following steps: (1) using amino acid to synthesize alkamine; (2) using the alkamine to synthesize the aziridine; (3) using the aziridine to synthesize-NHTs triamine; (4) removing protection to obtain triamine; and (5) cyclizing to obtain the pentabasic bicyclic guanidine. The method overcomes the defects of high cost of the purifying technique, complexity in operation, -78 DEG C of low temperature reaction, high danger coefficient, expensive prices of raw materials, high cost and difficulty in industrial production in the original technique; and the method has the advantages of simplicity, feasibility, excellent reaction temperature, cheap raw materials, simple operation, reduced cost and improved feasibility of industrial production.

Description

technical field [0001] The invention relates to the field of organic compound synthesis, in particular to a preparation method of chiral five-membered bicyclic guanidine. Background technique: [0002] Arginine exists in the active site of many enzymes and its guanidine side chain, usually in the form of protonated guanidinium ion, which can form double hydrogen bonds with biomolecules containing phosphate, nucleotide, and carboxylate effect. (References: C.L. Hannon, E.V. Anslyn, Bioorganic Chemistry Frontiers, Springer-Verlag: Berlin, Heidelberg, 1993, vol 3, 193.). Guanidine is one of the most basic neutral nitrogen compounds, and its derivatives are widely used in organic synthetic chemistry as a strong organic base. (References: Y. Yamamoto, S. Kojima, In The Chemistry of Amidines and Imidates; S. Patai, Z. Rappoport, Eds, John Wiley & Sons Inc.: New York, 1991, vol 2, pp 485.). [0003] [0004] It is expected that chiral guanidine derivatives can take advantage ...

AI Technical Summary

Problems solved by technology

[0017] This process starts from amino alcohols, and after a series of synthesis, guanidine 8 is finally obtained, but this process has many defects: 1. The first step of purification is column chromatography separation, which is costly and difficult to industrialize; 2. The second step of purification The method is column chromatographic separation, which is costly, cumbersome to operate, and difficult to scale up; 3. The fifth step of purification is column chromatographic separation, which is costly and cumbersome to operate; 4. The fourth step requires a low temperature reaction of -78 degrees and requires anhydrous Oxygen-free, cumbersome and complicated operation, high risk factor, high energy consumption, and difficult industrialization; 5. The dimethyl trithiocarbonate used in the fifth step is expensive and the cost is high

Images