Chiral synthesis method of pyrrolysine

Abstract

The invention discloses a brand-new chiral synthesis method of the 22nd natural amino acid, namely, pyrrolysine. The chiral synthesis method is characterized in that crotonaldehyde and ethyl nitroacetate are taken as starting reactants and are subjected to Michael addition, hydrogenation, construction of pyrrole ring precursor, ring closing and hydrolysis reactions to obtain a pyrrolysine lithium salt which is the stable existence form of pyrrolysine. The synthesis routine provided by the invention has the biggest advantage of adopting the key step of asymmetrical Michael additional reaction catalyzed by using an environment-friendly organic micromolecular catalyst, namely (2S)-2-[bi[3,5-bi(trifluoromethyl) phenyl][(trimethyl estersil) oxy]methyl]-pyrrolidine, and the key step of imine linkage construction under the catalysis of compound acid. Compared with the prior art, the chiral synthesis method disclosed by the invention has the advantages of short process, high efficiency, mild reaction condition, environment friendliness, high product enantioselectivity, high overall yield and the like. The synthesized chiral pyrrolysine is beneficial to researches on the effect of a chiral structure in biology.

Description

technical field [0001] The invention relates to a synthesis method of the twenty-second natural amino acid-pyrrolysine, which belongs to the field of organic synthesis. Background technique [0002] In 2002, two research groups of Joseph A. Krzycki and Michael Chan of Ohio State University discovered a new twenty-second natural amino acid—pyrrolysine in the methylaminomethyltransferase of methanogens. It is the twenty-second natural amino acid discovered so far. by right Methanosarcina barkeri The study on the crystal structure of monomethylamine determined that it is composed of (4R,5R)-4-methyl-pyrrole ring-5-carboxylic acid and L-lysine, and its specific chemical structure is as follows: [0003] [0004] The discovery of pyrrolysine, the twenty-second natural amino acid, can advance our basic biochemical research on the mechanism of how some archaeal bacteria produce methane; this novel amino acid is encoded by the stop codon UAG. In addition, the study of the mec...

AI Technical Summary

Problems solved by technology

However, subsequent research workers questioned its coupling step, thinking that the coupling reaction of (4R,5R)-4-methyl-pyrrole ring-5-carboxylic acid and L-lysine fragment in this route not repeatable

[0006] Domestic scholars' biological research on the 22nd natural amino acid-pyrrolysine is basically in a blank stage, and so far only a few scientists have translated research reports on pyrrolysine

In 2010, Luo Xiaoyan and other scholars from East China University of Science and Technology reported a method for synthesizing achiral pyrrolysine in Chinese patent CN101709047A, but the route is long and has 8 steps in total.

But the route is long, which is not conducive to operation and industrial production

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