Redesigning the synthesis of vidarabine via a multienzymatic reaction catalyzed by immobilized nucleoside phosphorylases

Abstract

The comparison between the biocatalyzed synthesis of araA here described and the chemical synthesis of this nucleoside showed that the enzymatic route is superior (less steps, milder conditions and reagents, easier downstream, lower E-factor).

Development of an immobilized biocatalyst based on Bacillus psychrosaccharolyticus NDT for the preparative synthesis of trifluridine and decytabine

“…Consequently, the use of a high pH value [35] and/or the presence of a co-solvent [5,38] can be required to achieve suitable product concentrations for the development of preparative and industrial processes. However, enzyme stability may be affected by reaction conditions different from the physiological ones.…”

Use of Immobilized Amine Transaminase from Vibrio fluvialis under Flow Conditions for the Synthesis of (S)‐1‐(5‐Fluoropyrimidin‐2‐yl)‐ethanamine

“…In fact, glycerol is routinely used to preserve proteins under storage . For this reason, glycerol has been used as an additive in some immobilization procedures; typically, the amount of glycerol does not exceed 20 % v/v . Furthermore, a recent report on Vf‐ ATA thermostability showed that this enzyme retains 100 % activity at 4 °C for more than 50 h, and 80 % activity when it is incubated at 25–37 °C.…”

Synthesis of Adenine Nucleosides by Transglycosylation using Two Sequential Nucleoside Phosphorylase‐Based Bioreactors with On‐Line Reaction Monitoring by using HPLC

“…This approach is preferred to shift the reaction equilibrium to the formation of the desired nucleoside. Recent examples of NP‐catalyzed transglycosylations have revealed the great practical potential of this enzymatic method for the production of nucleoside analogues …”

“…On this basis, uridine phosphorylase from Clostridium perfringens ( Cp UP), a NP with a substrate specificity directed to pyrimidine nucleosides, was immobilized on a silica monolithic column, and the resulting Cp UP‐IMER was connected to the Ah PNP‐IMER developed previously to perform the synthesis of adenosine analogues 8 – 10 (Scheme ) by a “two‐enzyme” transglycosylation.…”

“…These considerations prompted us to develop two independent bioreactors both for a better control of the multienzymatic reaction and to better highlight the performance of the silica‐based monolithic column. Nevertheless, the coimmobilization of Cp UP and Ah PNP was also attempted with the aim to mimic the “one‐pot, two‐enzyme” transglycosylation performed in batch mode for the synthesis of arabinosyladenine (araA, 10 ; Scheme ).…”