Liisa T. Kanerva

Approach to highly enantiopure β-amino acid esters by using lipase catalysis in organic media

Abstract Ethyl esters of ten alicyclic β-aminocarboxylic acids were resolved by lipase catalysis in organic solvents. The resolution was based on acylation of the amino group at the R-stereogenic centre with various 2,2,2-trifluoroethyl esters. An increase in the hydrophobic nature of the acyl donor enhanced the enantioselectivity and reactivity in the case of lipase SP 526 from Candida antarctica, while the opposite effect was observed with lipase PS from Pseudomonas cepacia. An unexceptional enantioselectivity enhancement was observed when 2,2,2-trifluoroethyl chloroacetate was used in the case of lipase PS catalysis.

Preparation of highly enantiopure β-amino esters by Candida antarctica lipase A

Abstract The enantioselectivities for the reactions of aliphatic β-substituted β-amino esters [RCH(NH 2 )CH 2 CO 2 Et with R=Me, Et, n -Pr, i -Pr, CHEt 2 , cyclohexyl and Ph] with butyl butanoate in neat butyl butanoate and with 2,2,2-trifluoroethyl butanoate in diisopropyl ether were studied in the presence of Candida antarctica lipase A. Enantioselectivities ranging from good ( E =70–100) to excellent ( E >100) were commonly observed, allowing gram-scale resolution of the substrates.

Combination of the lipase-catalysed resolution with the Mitsunobu esterification in one pot

Abstract A chemo-enzymatic method for the preparation of homochiral esters of 14 secondary alcohols with 100% theoretical yields is described in one pot through two steps: the lipase-catalysed kinetic resolution followed by the Mitsunobu esterification of the free alcohol enantiomer in situ in the resolution mixture. Mathematical equations which link the enzymatic and chemical steps were derived, resulting in an enantioconvergent synthetic tool for the preparation of chiral intermediates.

NOVEL (R)-OXYNITRILASE SOURCES FOR THE SYNTHESIS OF (R)-CYANOHYDRINS IN DIISOPROPYL ETHER

Abstract Apple, apricot, cherry and plum meal were prepared from the seeds or kernels of mature garden fruits. The preparations as well as almond meal were used as the source of (R)-oxynitrilase for the synthesis of aliphatic and aromatic cyanohydrins in diisopropyl ether in the presence of 0.1 M tartrate buffer [2% (v/v), pH 5.4]. Apple meal as the most favourable of the enzyme preparations accepts also sterically hindered aldehydes (e.g., pivalaldehyde) as substrates, leading to (R)-cyanohydrins with high enantiopurity (usually ee>90%).

Enzyme-catalysed synthesis of optically active aliphatic cyanohydrins

Abstract The enantioselective preparation of aliphatic (R)-cyanohydrins was studied using powdered almond meal, a rich source of mandelonitrile lyase, as a catalyst in organic solvent. The feasibility of powdered almond meal as a catalyst was compared to that of a purified enzyme preparation.

Biocatalysis for the preparation of optically active β-lactam precursors of amino acids

Abstract Enantioselective acylation of N -hydroxymethylated β-lactams in the presence of Pseudomonas sp. lipase afforded optically active precursors for the preparation of (1 R ,2)- and (2 S ,2 R )-2-aminocyclopentane- and (1 R ,2 S ,3 R ,4 S )- and (1 S ,2 R ,3 S ,4 R )-3-aminobicyclo[2.2.1]heptanecarboxylic acids. Due to the high enantioselectivity ( E = 90 and 62) and in order to minimize the enzymatic hydrolysis of the acylated products back to the starting alcohol, the reactions were performed in acetone.

Enantioselective lipase-catalyzed reactions of methyl pipecolinate: transesterification and N-acylation

Abstract The present research introduces the highly ( S )-selective ( E >>100) acylation at the secondary ring nitrogen of methyl pipecolinate as a novel resolution method with Candida antarctica lipase A. Catalysis by lipase B leads to reactions at the methyl ester function of the substrate in an almost non-enantioselective manner.

Approach to(R)- and (S)-ketone cyanohydrins using almond and apple meal as the source of (R)-oxynitrilase

Abstract The synthesis of aliphatic and aromatic (R)-ketone cyanohydrins through the addition of hydrogen cyanide to the corresponding ketones and the synthesis of the (S)-enantiomers through the kinetic resolution of racemic ketone cyanohydrins has been studied in the presence of almond or apple meal. Substrate tolerance of the (R)-oxynitrilases towards ketones (R1R2C=O) is highly restricted compared to that of structurally similar aldehydes, reactivity following the order of H > Me⪢Et for R2. In the case of aromatic methyl ketones reactivity difference (C6H5⪢p-MeC6H4 for R1) is notable.

(R)- and (S)-cyanohydrins using oxynitrilases in whole cells

Abstract Almond meal and Sorghum bicolor shoots were used as the sources of oxynitrilases for the preparation of a number ( R )- and ( S )-arylcyanohydrins, respectively, from the corresponding aldehydes in diisopropyl ether. Two different in situ methods were used to introduce hydrogen cyanide into the reaction mixture. In method 1, acetone cyanohydrin decomposes enzymatically and/or chemically to hydrogen cyanide. In method 2, hydrogen cyanide freely evaporates from a solution in diisopropyl ether from one compartment of the reaction vessel and ends up to the other where it dissolves into the reaction mixture.

Immobilised Burkholderia cepacia lipase in dry organic solvents and ionic liquids: A comparison

Lipase PS from Burkholderia cepacia in its free, commercial form (BCL-PS), immobilised in a sol–gel (BCLxero) and as a CLEA (BCL-CLEA) was tested in dry organic solvents, ionic liquids and their mixtures. Utilising the acylations of secondary alcohols 1–3 the influence of the enzyme preparation on its activity and enantioselectivity was studied. BCL-CLEA displays higher activity (initial rates) than BCLxero for all substrates in the ILs but loses its activity rapidly. Thus, BCLxero is suitable for kinetic resolution in ILs and in their mixtures with organic solvents. It is not possible to label one IL better than the other without taking the nature of the substrate into account. In neat solvents, the nature of the solvent affects enantioselectivity (E) only when furyl-substituted alcohol 2 serves as a substrate while variation in E is more evident for reactions in solvent mixtures.