Hexahydropyridine-alpha-carboxylic acid is used to prepare L-homoproline_Industrial additives

Background and overview of the use of hexahydropyridine-alpha-carboxylic acid in the preparation of L-homoproline

Hexahydropyridine-alpha-carboxylic acid, namely DL-homoproline, piperidine bromopyridine dihydrochloride (PA), is an important rigid cyclic non-protein amino acid, which can both The conformation of polypeptides can also be used as a multifunctional skeleton in the synthetic library of different compounds, so it is widely used in the preparation of many chiral drugs and biologically active substances. For example, the new generation of local anesthetic Ropivacaine, the antipsychotic drug Thioridazine, the immunosuppressant rapamycin and the anti-tumor antibiotic Sandramycin are all based on It is made from hexahydropyridine-alpha-carboxylic acid or its derivatives as the main raw material.

Hexahydropyridine-alpha-carboxylic acid is used to prepare L-homoproline Hexahydropyridine-alpha-carboxylic acid is used to prepare L-homoproline ^[1]

CN201410594932.3 reports a preparation method of L-homoproline, which is characterized by adding DL-homoproline and L-tartaric acid to the solvent, stirring and heating until all is dissolved, and then adding a catalyst, Raise the temperature to 65~75°C for synthetic mica, maintain it for 8-10 hours, concentrate under reduced pressure, and recover the solvent; add methanol, stir until the solid is fully dissolved, centrifuge, add activated carbon to the centrifuged solution to decolorize, vacuum filtrate, and pass the filtrate through NH3 ammonia solution to pH=8.5~9.0, filter, the filtrate is concentrated and crystallized, cooled and filtered to obtain L-homoproline. The process product of the invention has high yield, relatively low cost and good economic benefits.

Hexahydropyridine-alpha-carboxylic acid is used in the preparation of L-homoproline

CN201310644714.1 provides a method for producing tacrolimus by fermentation, which belongs to the field of biomedicine. In the method for producing tacrolimus by fermentation provided by the present invention, parameters such as the slant culture medium components, liquid culture medium components, seed liquid inoculation amount, fermentation culture medium components and other parameters of bacterial strain activation are optimized to maintain the stability of Streptomyces. growth activity and fermentation activity, and increase the production of tacrolimus; during the fermentation process, pipecolic acid is added to the fermentation medium, and its addition time and amount are optimized to reduce feedback inhibition of the product. , while increasing the production of the final product tacrolimus, making the final production of tacrolimus reach 385 μg/mL.

References

[1] CN201410594932.3 A kind of preparation method of L-homoproline

[2] [Chinese invention, Chinese invention authorization] CN201710288291.2 Extraction and separation method of L-pipecolic acid in recombinant Escherichia coli fermentation products [Public]/Extraction and separation of L-pipecolic acid in recombinant Escherichia coli fermentation products Method【Authorization】

[3] CN201310644714.1 Method for producing tacrolimus by fermentation