Miconazole intermediate biosynthesis method

Abstract

The invention relates to a miconazole intermediate biosynthesis method. The biosynthesis method is characterized in that a miconazole intermediate [(R)-2-chlorine-1-(2,4-dichlorophenyl)-ethanol] witha high chiral ee value (ee is greater than 99) is prepared by catalyzing a substrate 2-chlorine-1-(2,4-dichlorophenyl)ethanone by carbonyl reductase in an enzyme database of carbonyl reductase in a laboratory; the carbonyl reductase is Candida macedoniensis AKU 4588; an addition of the carbonyl reductase is 20-100 U / L; the catalyzed synthesis condition is characterized in that in a buffer solutionwith a pH value being 7.6-8.8, and the miconazole intermediate [(R)-2-chlorine-1-(2,4-dichlorophenyl)-ethanol] is synthesized by catalyzing a reaction of the substrate 2-chlorine-1-(2,4-dichlorophenyl) ethanone at the temperature of 30-40 DEG C and under condition of existence of Zn2+. The method mainly substitutes a traditional chemical synthetic method, reduces production cost and environment pollution, and the miconazole intermediate with the high chiral ee value (ee is greater than 99) is prepared by using a biological enzyme catalysis method.

Description

technical field [0001] The invention relates to a biosynthesis method of a miconazole intermediate, which belongs to the technical field of biocatalysis. Background technique [0002] Miconazole is a highly effective, safe and broad-spectrum antifungal drug, which is effective against almost all pathogenic fungi. Its mechanism is to inhibit the synthesis of sterols in the fungal cell membrane, affect the permeability of the cell membrane, inhibit the growth of fungi, and lead to death. Concentrations below 4 µg / mL can inhibit most of the clinically isolated fungi, among which Cryptococcus neoformans, Candida and Pleurosporum are sensitive to this product, Blastomyces dermatitidis and Histoplasma are highly sensitive to this product, but Aspergillus Mold is poor. In addition, miconazole also has antibacterial effects on Staphylococcus aureus, Streptococcus, Gram-positive cocci and anthrax. [0003] (R)-2-Chloro-1-(2,4-dichlorophenyl)ethanol is an important intermediate in ...

AI Technical Summary

Problems solved by technology

However, chemical synthesis is mainly used at present, but this method needs to use expensive chiral ligand (S, S)-TsDPEN and metal reagent [Ru (p-cymene)Cl2] 2, the product yield is low, chiral ee The value is not high, the chemical production cost is large and the environment is not optimized, and it is not suitable for large-scale production

(R)-2-Chloro-1-(2,4-dichlorophenyl)ethanol has not been reported yet