Ionic Liquids: Efficient Media for the Lipase-Catalyzed Michael Addition

Abstract

Recently, ionic liquids (ILs) have been regarded as ideal media for non-aqueous bio-catalysis. In this work, the synthesis of warfarin by the lipase-catalyzed Michael addition in IL media and the parameters that affected the warfarin yield were investigated. Experimental results demonstrated that the chemical structures of the ILs were a major factor for influencing the warfarin yield. The ILs containing the NTf2– anion were suitable reaction media due to the high chemical stability of this anion. The incorporation of the hydroxyl group on the IL cation significantly improved the lipase activity due to the H2O-mimicking property of this group. The lipase activity decreased by increasing the alkyl chain length on the IL cation due to the non-polar domain formation of the IL cation at the active site entrance of lipase. The ILs and lipase could be reused no less than five times without reduction in the warfarin yield.

Aqueous ionic liquids redistribute local enzyme stability via long-range perturbation pathways

“…While this is beneficial in some cases, e.g., for the reduction of viscosity to increase molecular diffusion [10] , [11] , other effects such as a drastically decreased solvation potential can be limiting for aqueous IL (aIL) use [12] , [13] , [14] . Consequently, studying aIL has gained much attention and yielded numerous applications [4] , e.g., as environmental-friendly alternatives for commonly used organic solvents in organic synthesis [1] , [15] , [16] or as (co–)solvents in biocatalysis [17] , [18] , [19] , [20] and green industrial processes [14] , [21] , [22] , [23] , [24] .…”

Stereoselective Promiscuous Reactions Catalyzed by Lipases

“…Some interest has been focused on the synthesis of warfarin 12 through a biocatalyzed Michael addition of 4-hydroxycoumarin to benzylideneacetone in wet [43] or anhydrous DMSO [44] in the presence of different lipases, but despite the obtained yield of the target drug (85-87%) being satisfactory, the enantioselectivity was quite low (Scheme 14). More recently, the use of ionic liquids as reaction medium was shown feasible for this reaction, but detrimental for the enzyme enantioselectivity, leading to racemic warfarin in >95% yield [45].…”

“…More recently, the use of ionic liquids as reaction medium was shown feasible for this reaction, but detrimental for the enzyme enantioselectivity, leading to racemic warfarin in >95% yield [ 45 ].…”