Enzymatic resolution of sec-butylamine

Resolution of (±)-sec-butylamine by Candida antarctica lipase provided a very low enantiomeric excess of the residual amine when either ethyl or vinyl butyrate was used as the acylating agent. The enantiomeric excess was increased by using ethyl esters of long chain fatty acids. The rate of the reaction was increased by using methyl t-butyl ether as a solvent. (S)-sec-Butylamine of very high enantiomeric excess was obtained by C. antarctica lipase catalyzed acylation with ethyl decanoate in methyl t-butyl ether.     

Enzymatic kinetic resolution of ketorolac

Ketorolac 1 was resolved into each enantiomer by interesterification using lipase B from Candida antarctica. The acid reacted with various alcohols and the ester and acid were resolved up to >99% e.e. when reacted with octanol, which was the best result. To increase reactivity and enantioselectivity, the experimental conditions were adjusted by varying temperature, solvent, alcohols and reaction time.     

Enzymatic resolution of racemic lactones

PPL, HLE or PLE enzymatic resolution of racemic γ, δ and ε-lactones gives optically active lactones (ee: 60 to 90%).     

Enzymatic resolution of 2-trifluoromethylalanine

Hog kidney aminoacylase catalyzes hydrolysis of N-trifluoroacetyl-R(+)2-trifluoromethylalanine with 99.1% enantioselectivity.     

Enzymatic kinetic resolution of Morita-Baylis-Hillman acetates

Racemic Morita-Baylis-Hillman adducts derived from the reaction of acrylonitrile with benzaldehyde, cinnamaldehyde and hydrocinnamaldehyde have been successfully resolved by means of enzymatic kinetic resolution. The (+)-alcohol products were isolated with 94–97% ee after lipase-mediated enantioselective hydrolysis of the corresponding acetates. Mosher’s double derivatisation protocol was applied to these isolated products and the absolute configuration of the alcohols was found to be (S) for all three substrates.     

Enzymatic kinetic resolution of tropic acid

A new strategy has been developed for the CAL-B catalysed kinetic resolution of tropic acid by which both enantiomers of tropic acid can be obtained in good enantiomeric excess. (R)-Tropic acid was synthesised with 90% ee and (S)-tropic acid butyl ester in 99% ee by the hydrolysis of tropic acid butyl ester. The other enantiomers were available through the enzymatically catalysed reaction of tropic acid lactone with butanol to give (S)-tropic acid lactone and (R)-tropic acid ester in >98% ee.     

Enzymatic resolution of substituted mandelic acids

A series of substituted mandelic acids were prepared and subjected to enzymatic resolution utilizing Lipase PS ‘Amano’.     

Enzymatic resolution of chiral phosphinate esters

The bacterial phosphotriesterase has been shown to catalyze the stereoselective hydrolysis of phosphinate esters. The wild-type enzyme preferentially hydrolyzes the SP-enantiomers of methyl phenyl p-X-phenylphosphinate esters by 3 orders of magnitude. The mutant enzyme, I106T/F132A/H254G/H257W, exhibits the opposite stereoselectivity and hydrolyzes the RP-enantiomer up to 30 times faster than the corresponding SP-enantiomer. The enantiomerically pure phosphinate esters, prepared from the kinetic resolution of racemic mixtures, can serve as the entry point for the chemoenzymatic preparation of P-chiral phosphines and phosphine oxides.     

Enzymatic resolution of stereoisomers of 2-iodocyclohexanol

All four optically active stereoisomers of 2-iodocyclohexanol were synthesized. Their enantiomeric purity was determined upon derivatization with Mosher’s acid, absolute configuration have been established by chemical correlation.     

Enzymatic resolution of 2-dialkylaminomethylcyclopentanols and -cycloheptanols

Extensive lipase screening was performed in relation to the asymmetric acetylation of rac-2-dialkylaminomethylcyclanols 1–5. The lipase PS- and Novozym 435-catalysed resolutions of compounds 1–5 were based on asymmetric acylation of the secondary OH group at the R-stereogenic centre with various vinyl esters, in different organic media. High enantioselectivity (E>200) was observed when vinyl acetate was used as acylating agent, with diethyl ether or with diisopropyl ether as solvent. The reaction rates were markedly affected by the size of the alicyclic ring, and by the solvent.     

Enzymatic resolution of five membered heterocyclic bromohydrins

The lipase catalyzed resolution of trans-3,4-tetrahydrofuran and pyrrolidine bromohydrins by acylation or hydrolysis of their acylated derivatives has been studied. For both heterocycles, the best enantioselectivity was obtained using Candida antarctica lipase B as the catalyst in the hydrolytic processes. The enantiomerically pure bromohydrins are useful intermediates for the preparation of 3,4-fuctionalized cis-heterocycles.     

Enzymatic resolution of racemic secondary cyclic allylic alcohols

The resolutions of five racemic cyclic alcohols: 6,6-dimethylcyclohex-2-en-1-ol (±)-5, 4,4-dimethylcyclohex-2-en-1-ol (±)-7, 5,5-dimethylcyclohex-2-en-1-ol (±)-11 and isomeric trans-(±)-13 and cis-piperitols (±)-14 are presented. They were resolved by enzymatic esterification with vinyl esters or by enzymatic hydrolysis of their racemic esters in phosphate buffer. The following lipases were used as biocatalysts: Novozyme 435 (Candida antarctica), Amano PS (Burkholderia cepacia) and lipase from Candida cylindracea. All isomers of alcohols were obtained with at least 96% ee.     

Enzymatic resolution of α-tetralols by CALB-catalyzed acetylation

A series of homochiral α-tetralols, as well as their respective acetates, has been obtained by esterification of racemic tetralols, using Candida antarctica lipase (CALB—Novozym^® 435) as the biocatalyst. This enzyme is shown to be highly efficient for the kinetic resolution of the substrates studied, affording the (+)-tetralols and the (+)-acetates in excellent enantiomeric excess (up to >99%) and very good yields (>40%).     

Enzymatic enantiomeric resolution of phenylethylamines structurally related to amphetamine

Both enantiomers of several phenylethylamines, structurally related to amphetamine, have been prepared in good yields and excellent enantiomeric purity by enzymatic kinetic resolution using CAL-B and ethyl methoxyacetate as the acyl donor. In the case of the 4-hydroxyderivative of amphetamine (compound 4i), the S enantiomer racemized possibly in a dynamic kinetic resolution (DKR) under the enzymatic conditions used.     

Enzymatic resolution of a 1,2-cyclic sulphite glycerol derivative

cis-2-Oxo-5-hydroxymethyl-1,3,2-dioxathiolane 2a can be efficiently resolved by a lipase from Pseudomonas cepacia-catalysed acylation reaction with vinylbutyrate. Compound 2a was directly prepared from glycerol in one step. This first lipase-catalysed resolution of a cyclic sulphite derivative provides a potentially useful activated chiral synthon.     

Enzymatic kinetic resolution of racemic cyanohydrins via enantioselective acylation

Enzymatic kinetic resolution of a series of aromatic and aliphatic cyanohydrins in organic media has been investigated. The behavior of potential lipases, molecular sieves, acyl reagent, reaction temperature, and organic solvents on the kinetic resolution was studied. The influence of substrate structure, steric, and electronic nature and position of the aryl substituent on the enantioselectivity was discussed. Under the optimized reaction conditions, good enantioselectivity could be achieved for most of the investigated compounds. Specifically, substrates 1a, 1c, 1d, 1f, 1u could be resolved with the kinetic enantiomer ratio (E) higher than 200.     

Enzymatic resolution and evaluation of enantiomers of cis-5'-hydroxythalidomide

The straightforward synthesis of both enantiomers of cis-5'-hydroxythalidomide, a major metabolite of thalidomide, has been accomplished by enzymatic kinetic resolution of a racemic substrate catalyzed by Pseudomonas stutzeri lipase TL. cis-5'-Hydroxythalidomide shows resistance to racemization (and epimerization) at physiological pH. A tube formation assay to assess the ability to inhibit angiogenesis revealed that cis-5'-hydroxythalidomides are inactive.     

Enzymatic optical resolution via acylation-hydrolysis on a solid support

By taking advantage of the reversibility of the thermolysin-catalysed amide synthesis-hydrolysis reaction on a solid support, both L,L and L,D diastereoisomers of dipeptides and L-amino acids are accessible in good yields starting from enantiomeric mixtures of amino acids.     

Enzymatic resolution of alicyclic 1,3-amino alcohols in organic media

Racemic cis- and trans-2-aminocyclohexane-1-methanol and cis- and trans-2-amino-4-cyclohexene-1-methanol were resolved via lipase-catalysed O-acylation of their Z derivatives, using vinyl butyrate in different ether solvents. In accordance with the empirical rule, most of the screened lipases preferred the 1S enantiomer.