Method for online synthesizing 5'-O-palmitoyl uridine in lipozyme catalysis mode

Abstract

The invention discloses a method for online synthesizing 5'-O-palmitoyl uridine in a lipozyme catalysis mode .The method includes the steps that dimethyl sulfoxide and tert-amyl alcohol with the volume ratio of 1:(8-16) serve as a reaction solvent, uridine and palmitic acid vinyl ester with the molar ratio of 1:(5-13) serve as raw materials, 0.5 g to 1.0 g of lipozyme TLIM serves as a catalyst, the raw materials and the reaction solvent are placed into an injector, a reaction channel of a microfluidics channel reactor is evenly filled with the lipozyme TLIM, and the raw materials and the reaction solvents are continuously led into a reaction channel device under pushing of an injection pump for an acylation reaction, wherein the inner diameter of the reaction channel of the microfluidics channel reactor is 0.8 mm to 2.4 mm, the length of the reaction channel is 0.5 m to 1.0 m, the temperature of the acylation reaction is controlled to be 15 DEG C to 50 DEG C, the concentration of the uridine in the reaction system is 0.03 mmol / mL to 0.07 mmol / mL, and the time of the acylation reaction is 20 min to 35 min; reacted liquid is online collected through a product collector and subjected to conventional aftertreatment, and the 5'-O-palmitoyl uridine is obtained .The method has the advantages of being short in reaction time and high in selectivity and yield.

Description

(1) Technical field [0001] The invention relates to a lipase-catalyzed online controllable selective synthesis of 5'-O-palmitoyluridine (2) Background technology [0002] Nucleoside drugs play an important role in the treatment of viral diseases. Among the antiviral drugs currently used clinically, nucleoside drugs account for more than 60%. Most nucleoside compounds are polyhydroxy compounds, which have defects such as high polarity, low intestinal permeability, poor fat solubility, high toxicity and side effects, and low oral bioavailability. After the nucleoside compound is modified by esterification, its fat solubility can be enhanced, its pharmacological activity can be improved, and its oral bioavailability can be improved. In the usual chemical esterification process, multiple hydroxyl groups may participate in the esterification, and the product is a mixture of monoester and polyester, so it needs to be protected by "group protection——esterification——deprotection g...

AI Technical Summary

Problems solved by technology

[0006] At present, many domestic and foreign scholars have studied the enzyme-catalyzed synthesis of nucleoside acylation in organic media, but this method mostly uses acylase for catalysis, which often requires a long reaction time (12-24h), and The conversion rate and selectivity of the reaction are not high, so we studied the lipase-catalyzed online synthesis of 5'-O-palmitoyluridine in a microchannel reactor, aiming to find an efficient and environmentally friendly 5'-O-palmitoyluridine On-line controllable and selective synthesis of acyluridines

Images