Enzymatic synthesis of nucleoside analogues from uridines and vinyl esters in a continuous-flow microreactor

Abstract

We achieved the effective controllable regioselective acylation of the primary hydroxyl group of uridine derivatives catalyzed by Lipase TL IM from Thermomyces lanuginosus with excellent conversion and regioselectivity.

The Impact of Recent Developments in Technologies which Enable the Increased Use of Biocatalysts

“…Recently, the enzymatic synthesis of nucleoside analogues using immobilized Lipozyme® catalyzed transesterification has been reported . The regioselective reaction was carried out using a microflow reactor (Scheme ).…”

Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus

“…In our previous studies, some works about continuous-ow enzymatic methods were reported. [35][36][37][38] The objective of this research was to nd an efficient and green continuous-ow enzymatic method of purine nucleoside esters (Scheme 1).…”

In vitro antimicrobial, physicochemical, pharmacokinetics and molecular docking studies of benzoyl uridine esters against SARS-CoV-2 main protease

“…doxifluridine) have shown higher activities in the treatment of viral and cancer treatment, their efficiency is sometimes reduced by the appearance of resistance mechanisms (De Clercq, 2011 ). Hence, search for newer analogues of uridine (nucleoside) got more attention especially esterification of its sugar moiety (Du et al, 2018 ). However, investigations indicated that selective esterification (acylation) uridine ( 1 ) creates difficulties due to the presence of one 1° OH group, two 2° OH groups and a NH group.…”

“…However, investigations indicated that selective esterification (acylation) uridine ( 1 ) creates difficulties due to the presence of one 1° OH group, two 2° OH groups and a NH group. Hence, various methods like direct acylation (Matin, Bhattacharjee, et al, 2019 ; Matin, Bhuiyan, et al, 2019 ; Matin, Chakraborty, et al, 2020 ; Matin, Hasan, et al, 2020 ; Matin, Roshid, et al, 2020 ), dibutyltin oxide (DBTO) method (Kabir, Matin, & Kawsar, 1998 ; Kabir, Matin, Kawsar, & Anwar, 1998 ; Kabir, Matin, Mridha, et al, 1998 ; Kabir et al, 1997 , 1998a , 1998 b), coupling technique (Steglich esterification) (Clayden et al, 2012 ), protection–deprotection (Matin et al, 2017 ) and enzymatic method (Du et al, 2018 ) were reported. Among these methods, direct method generally furnished 5′- O -substituted esters (Kabir, Matin, & Kawsar, 1998 ; Kabir, Matin, Kawsar, & Anwar, 1998 ; Kabir, Matin, Mridha, et al, 1998 ; Kabir et al, 1997 , 1998a , 1998 b) whereas DBTOmethod gave 3′- O -substituted products (Kabir, Matin, & Kawsar, 1998 ; Kabir, Matin, Kawsar, & Anwar, 1998 ; Kabir, Matin, Mridha, et al, 1998 ; Kabir et al, 1997 , 1998a , 1998 b, 2002 ).…”