REGULAR ARTICLE Lipase‐catalyzed enantioselective transesterification of prochiral 1‐((1,3‐dihydroxypropan‐2‐yloxy)methyl)‐5,6,7,8‐ tetrahydroquinazoline‐2,4(1H,3H)‐dione in ionic liquids Renata Kołodziejska 1 | Renata Studzińska 2 | Hanna Pawluk 1 1 Department of Biochemistry, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland 2 Department of Organic Chemistry, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland Correspondence Renata Kołodziejska, Department of Biochemistry, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Karłowicza 24, 85‐092 Bydgoszcz, Poland. Email: renatakol@poczta.fm Abstract The application of ionic liquids as solvents for transesterification of prochiral pirymidine acyclonucleoside using lipase (EC 3.1.1.3) Amano PS from Burkholderia cepacia (BCL) is reported. The effect of using medium reaction, acyl group donor, and temperature on the activity and enantioselectivity of BCL was studied. From the investigated ionic solvents, the hydrophobic ionic liquid [BMIM]PF 6 ] was the preferred medium for enzymatic reactions. How- ever, the best result was obtained in the mixture [BMIM][PF 6 ]:TBME (1:1 v/v) at 50°C. Enzyme activity and selectivity in [BMIM][PF 6 ]:TBME (1:1 v/v) was slightly higher in than in conventional organic solvents (for example, TBME), and in this condition, good activity and enantioselectivity were associated with unique properties of ionic liquid such as hydrophobicity and high polarity. Inde- pendently of solvents, monester of (R)‐configuration was obtained in excess. Under optimal conditions, desymmetrization of the prochiral compound using different acyl donors was performed. If vinyl butyrate was used as the acylating agent, BCL completely selectively acylated enantiotopic hydroxyl groups. KEYWORDS acyclonucleoside, biocatalysis, desymmetrization of prochiral groups, hydrolases, ionic liquids 1 | INTRODUCTION An effective enzymatic catalysis should be performed under conditions optimal for a biocatalyst perfor- mance. 1-3 Hence, it is essential to select an appropriate reaction medium. Typical organic solvents for the enzy- matic syntheses include mainly alkanes (hexane, cyclo- hexane with logP > 3), aromatics (toluene, benzene with logP 2.5 and 2, respectively), haloalkanes (chloroform, dichloromethane with logP 2 and 0.85, respectively), and ethers (diisopropyl ether, tert‐butylmethyl ether, diethyl ether with logP 1.9, 1.3, 0.85, respectively). 1,2 In most cases, an enzymatic catalysis becomes less effective with an increase in a solvent polarity. Solvents, such as dimethylformamide or dimethyl sulfoxide are able to dissolve and denature the protein. Dimethyl sulfoxide dis- solves the protein by forming the hydrogen bonding with amide hydrogen. This, together with the disintegration of water monolayer, causes the protein denaturation. In a nonaqueous environment (considering the minimum nec- essary amount of water), the charged sides of the surface residues are found to fold back into the surface of the pro- tein, thus reducing the surface area. 4,5 The consequence of this phenomenon is the increase in an enzyme stability in an organic solvent. 4 Some ionic liquids constitute a bridge between con- ventional organic solvents and physiological enzyme envi- ronment. They provide exceptional activity of catalytic proteins, which allows efficient and selective reaction catalysis. Ionic liquids are organic salts composed of large Received: 5 July 2017 Revised: 5 October 2017 Accepted: 6 October 2017 DOI: 10.1002/chir.22787 Chirality. 2017;1–9. © 2017 Wiley Periodicals, Inc. wileyonlinelibrary.com/journal/chir 1