Lipase-mediated Resolution Research Articles

Lipase-mediated resolution of octahydro-3,3,8a-trimethyl-1-naphthalenol, a key intermediate in the total synthesis of lactaranes and marasmanes

The bicyclic alcohol (1α,8aα)-1,2,3,4,6,7,8,8a-octahydro-3,3,8a-trimethyl-1-naphthalenol (±)- 1 was resolved using Candida rugosa lipase-mediated esterification with vinyl acetate ( E=72). The absolute configuration of the remaining isomer was determined by X-ray analysis of its 4-chloro-3-nitrobenzoate. The observed stereochemical preference of the enzyme is in line with the rule formulated by Kazlauskas et al. [Kazlauskas, R. J.; Weissfloch, A. N. E.; Rappaport, A. T.; Cuccia, L. A. J. Org. Chem. 1991, 56, 2656–2665]. The resolved alcohol is a useful chiral synthon for natural lactarane and marasmane sesquiterpenes.

Synthesis of the four enantiomerically-pure isomers of 15-F2t-isoprostane

Syntheses of the four enantiomerically-pure isomers of 15-F2t-isoprostane are described. The key step is the lipase-mediated resolution of a pseudo-meso diol, to give the regioisomeric acetates in high enantiomeric purity. Improved procedures for the preparation of the pseudo-meso diol are also reported.

Lipase-mediated resolution of 2-hydroxymethyl-1-iodoferrocene: synthesis of ferrocenes and biferrocenes with planar chirality

Racemic 2-hydroxymethyl-1-iodoferrocene (±)- 1 was subjected to esterification in the presence of lipase from Candida antarctica (Novozym ® 435) to afford (1 S,2 S)-2-acetoxymethyl-1-iodoferrocene (−)- 2 having 89% ee and unreacted (1 R,2 R)-2-hydroxymethyl-1-iodoferrocene (+)- 1 in enantiopure form. A single enantiomer of 2-hydroxymethyl-1-iodoferrocene gave easy access to new ferrocenes and biferrocenes possessing only planar chirality.

Chemo-enzymatic synthesis of ( S)-α-cyano-3-phenoxybenzyl alcohol

A chemo-enzymatic process for the preparation of ( S)-α-cyano-3-phenoxybenzyl alcohol ( S-CPBA), an important intermediate in the synthesis of many pyrethroids, was developed. The process consists of four stages, including lipase-mediated resolution. The first stage, the synthesis of racemic α-cyano-3-phenoxybenzyl acetate (CPBAc) from m-phenoxybenzaldehyde ( m-PBA) and sodium cyanide in the presence of a phase transfer catalyst, resulted in a 75% yield with 95% purity. The second key step is the resolution of the racemic ester by a highly enantioselective lipase from Pseudomonas sp. The immobilized enzyme carried out the transesterification reaction to nearly full conversion (46% out of 50%) with an enantiomeric excess of >96%. The enzymatic reaction was accomplished in a batch system as well as in a fluidized bed column. The reaction was found to be inhibited by accumulation of the product and to a lesser extent, by the aldehyde. The separation of the enantiomerically pure alcohol from the undesired ester was performed by chromatographic techniques, as well as by extraction with hexane. The final racemization step of the ( R)-ester was easily attained with the use of triethylamine in diisopropyl ether or toluene. The process was shown to be feasible on a gram scale and shows potential for scale up.

Chemoenzymatic synthesis of ( R)-(+)- α-(4-fluorophenyl)-4-(2-pyrimidinyl)-1-piperazinebutanol and ( R)-(+)- α-(4-fluorophenyl)-4-methyl-1-piperidinebutanol as potential antipsychotic agents

A chemoenzymatic straightforward synthesis of (R)-(+)-α-(4-fluorophenyl)-4-methyl-1-piperidinebutanol ( 2) and ( R)-(+)- α-(4-fluorophenyl)-4-(2-pyrimidinyl)-1-piperazinebutanol ( 3), two potential antipsychotic agents, has been developed by two different approaches involving lipasemediated resolution of the racemic compounds or through asymmetrization of the precursor alcohol 4. A second enzymatic resolution followed by condensation of (R)- 4 with 4-methylpiperidine ( 6) or 1-(2-pyrimidinyl)piperazine ( 7) leads to (R)- 2 and (R)- 3 in good chemical and excellent optical yields (>99% ee).

Lipase-Mediated Resolution of Indene Bromohydrin

Lipase-Mediated Resolution of Indene Bromohydrin

Lipase-Mediated Resolutions of 1-Aryl-3-Buten-1-ols

Racemic mixtures of 1-aryl-3-buten-1-ols were separated with high enantioselectivity by a lipase-mediated acetylation with vinyl acetate. The effects of the nature, position, and spatial requirements of the phenyl-ring substituents on the separation efficacy were investigated.

Lipase-mediated resolution and higher-order cycloaddition of substituted tricarbonyl ( η6-cycloheptatriene)chromium(0) complexes

A series of substituted cycloheptatriene-Cr(CO) 3 complexes were resolved enzymatically, and the resultant chiral, non-racemic complexes underwent higher-order photocycloaddition to afford enantiomerically-enriched cycloadducts in high chemical yield.

Lipase-mediated resolution of racemic 2-hydroxymethyl-1-methylthioferrocene

Both enantiomers of 2-hydroxymethyl-1-methylthioferrocene have been obtained with high optical purity by lipase-catalysed resolution of the racemate.

An Expedient Route to Optically Pure 1-Butyne-3,4-diol from 2,5-Dihydrofuran

Optically pure 1-butyne-3,4-diol has been obtained expediently in a satisfactory overall yield from 2,5-dihydrofuran on sequential epoxidation, nucleophilic cleavage, lipase-mediated resolution, and base-induced double elimination.

Lipase-Mediated Resolution of Inden-1-ol.

Optically pure inden-1-ol has been obtained efficiently in both enantiomeric forms via kinetic deacylation of racemic 1-acetoxyindene using lipase PS.

Enantiocontrolled route to natural products using chiral equivalents of cyclopentenone and cyclohexenone

Abstract

A short synthesis of 3(r)-hydroxy-2(R)-isopropyltetrahydrothiophene: A precursor to a high-affinity P 2-ligand of HIV-1 protease inhibitors

The title compound was synthesized in a 6 step sequence involving an efficient lipase-mediated resolution of racemic 3-hydroxy-2-isopropyltetrahydrothiophene.

Enzymatic resolution of N,N-dialkyl-3-hydroxy-4-pentenamides, unsuccessful in resolution by the Katsuki-Sharpless asymmetric epoxidation

An immobilized lipase-mediated resolution of secondary allylic alcohols 1 and 2 with which the Katsuki-Sharpless asymmetric epoxidation is unsuccessful is described.

Synthesis of Optically Active 4-Benzyloxymethyl- and 4-(4-Methoxyphenoxy)methylbuten-2-olides via Lipase-Mediated Resolution

A new preparation of optically active 4-benzyloxymethyl- and 4-(4-methoxyphenoxy)methylbuten-2-olides has been developed by employing lipase-mediated resolution and palladium-mediated carbomethoxylation as key steps

ChemInform Abstract: Lipase‐Mediated Resolution of 2‐Cyclohexen‐1‐ols as Chiral Building Blocks en route to Eburnane Alkaloids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Improved lipase-mediated resolution of mandelic acid esters by multivariate investigation of experimental factors

Lipase catalyzed stereoselective acylation of butyl mandelate was studied. The determining role of solvent and acylating agent was pointed out and a considerable inhibitory effect due to mandelic acid was observed by screening different lipases. Finally, the performance of the reaction was appreciably improved thank to a multivariate approach.

Lipase-mediated resolution of 2-cyclohexen-1-ols as chiral buildingblocks en route to eburnane alkaloids

Lipase catalyzed esterification of several 2-cyclohexen-1-ols proceeds with excellent enantioselectivity leading to ( S)-enantiomers as promising chiral building blocks en route to eburnane alkaloids

Efficient Chiral Route to a Key Building Block of 1,25-Dihydroxyvitamin D3via Lipase-Mediated Resolution

Racemic ethyl 5-hydroxy-1-cyclopentenecarboxylate [(±)-4] was resolved with complete enantiospecificity via kinetic acetylation in tert-butyl methyl ether in the presence of lipase PS which furnished optically pure (R)-acetate [(R)-5] and (S)-alcohol [(S)-4] both in nearly quantitative yields after silica gel column chromatography. (R)-Alcohol [(R)-4] obtained from (R)-5 was transformed into 1-ethynylbicyclo[3.1.0]hexan-2-one (3), a key building block of 1,25-dihydroxyvitamin D3 (1), in eight steps in 30% overall yield.

Lipase-mediated homotopic and heterotopic double resolutions of a planar chiral organometallic alcohol

(±)-Tricarbonyl η6-3-methylbenzyl alcohol)chromium was resolved to of ∼100%e.e. and of 92%e.e. by lipase-catalyzed transesterifications arranged in homotopic and heterotopic double resolutions.