Kinetic Resolution Of Racemic Alcohols Research Articles

SCOPE AND LIMITATIONS OF THE USE OF NICOTINOPROTEIN ALCOHOL DEHYDROGENASE FOR THE COENZYME-FREE PRODUCTION OF ENANTIOPURE FINE-CHEMICALS

Nicotinoprotein alcohol dehydrogenases are enzymes that contain non-dissociable NAD(P)(H) in the active site. The suitability of a nicotinoprotein alcohol dehydrogenase as coenzyme-independent alternative to classic alcohol dehydrogenases for enantioselective synthetic applications was studied. To this end the NADH-containing nicotinoprotein, np-ADH, from Rhodococcus erythropolis DSM 1069 was used as a model enzyme in different types of conversion: asymmetric synthesis, kinetic resolution and racemization. The enzyme was found to catalyze the asymmetric reduction of ketones using cheap reductants, such as ethanol, with high stereoselectivity, but the reaction was too slow to obtain good yields. Kinetic resolutions of racemic alcohols failed due to dismutation of the aldehyde that was used as cosubstrate. Racemization of a secondary alcohol via the corresponding ketone could not be achieved, which was due to an unidentified side reaction. This evaluation shows that, for developing biotransformations of industrial interest using nicotinoprotein alcohol dehydrogenases, the attention should be focused on enzymes with a higher reactivity towards prochiral ketones and secondary alcohols.

ChemInform Abstract: Hydrolase-Catalyzed Kinetic Resolutions of Chiral Alcohols: Mechanistic Study on the Origin of the Enantioselectivity

Mechanistic studies on the enantioselectivity in the hydrolase-catalyzed kinetic resolutions of racemic alcohols are described. Based on kinetic measurements, molecular orbital calculations and computer modeling with X-ray crystal structures of several lipases, we proposed the transition-state model that is consistent with the experimental observations such as (i) high enantioselectivity, (ii) broad substrate specificity and (iii) an empirical rule (R-preference for secondary alcohols). A large secondary alcohol having a tetraphenylporphyrin as the substituent was successfully resolved by several lipases, demonstrating the validity of our transition-state model. The S-preference of subtilisins for secondary alcohols was rationalized by applying the protocol used in the transition-state model for lipases to subtilisins. We also found that the lipasecatalyzed transesterifications of chiral alcohols in organic solvents can proceed even at -40°C. Interestingly, theE value increased with decreasing temperature, and a linear relationship was observed between In E and 1/T, from which the ΔΔH‡and ΔΔS‡ values were calculated. These thermodynamic parameters were useful for investigating the mechanism of the enantioselectivity of the hydrolases toward chiral alcohols.

加水分解酵素を用いた不斉アルコールの速度論的光学分割 エナンチオ選択性の発現機構

Mechanistic studies on the enantioselectivity in the hydrolase-catalyzed kinetic resolutions of racemic alcohols are described. Based on kinetic measurements, molecular orbital calculations and computer modeling with X-ray crystal structures of several lipases, we proposed the transition-state model that is consistent with the experimental observations such as (i) high enantioselectivity, (ii) broad substrate specificity and (iii) an empirical rule (R-preference for secondary alcohols). A large secondary alcohol having a tetraphenylporphyrin as the substituent was successfully resolved by several lipases, demonstrating the validity of our transition-state model. The S-preference of subtilisins for secondary alcohols was rationalized by applying the protocol used in the transition-state model for lipases to subtilisins. We also found that the lipasecatalyzed transesterifications of chiral alcohols in organic solvents can proceed even at -40°C. Interestingly, theE value increased with decreasing temperature, and a linear relationship was observed between In E and 1/T, from which the ΔΔH‡and ΔΔS‡ values were calculated. These thermodynamic parameters were useful for investigating the mechanism of the enantioselectivity of the hydrolases toward chiral alcohols.

Resolution and synthesis of optically active alcohols with immobilized water-soluble proteins from green pea, soybean and buckwheat as new bio-catalysts.

Kinetic resolution of racemic alcohols, (+/-)-1-(4-substituted phenyl)ethanol and (+/-)-1-(2-naphthyl)ethanol, was done with immobilized green pea, soybean, or buckwheat proteins. The resolution was done stereoselectively by oxidizing only one enantiomer of a racemic alcohol to leave an optically active alcohol with a high purity. In addition, each protein could be reused consecutively at least three times without any decrease of yield or optical purity.

ChemInform Abstract: Nonenzymatic Kinetic Resolution of Racemic Alcohols Through an “ Induced Fit” Process.

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.

Nonenzymatic Kinetic Resolution of Racemic Alcohols through an “Induced Fit” Process

Nonenzymatic Kinetic Resolution of Racemic Alcohols through an “Induced Fit” Process

Estramicins: a novel cyclic diyl precursor derived from estradiol

The estradiol derived ynone 2 is obtained via a 13 step sequence starting from estrone. One of the key-steps involves the addition to estrone derivative 3 of the lithio derivative 8. Obtention of the latter in enantiomerically pure form involves the lipase mediated kinetic resolution of racemic alcohol (±) 5. The triethylamine induced elimination of dimesylate 15 leads to the Bergman precursor 16, the cyclization of which at 25°C is estimated at t 1 2 = 20 min.

ChemInform Abstract: Amplification of Enantioselectivity in Biocatalyzed Kinetic Resolution of Racemic Alcohols.

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.

Amplification of enantioselectivity in biocatalyzed kinetic resolution of racemic alcohols

Amplification of enantioselectivity in biocatalyzed kinetic resolution of racemic alcohols

有機溶媒中での酵素触媒不斉反応の設計と光学活性医薬品合成への応用

New strategy of lipase-catalyzed asymmetric reactions is described. Chiral 2-O-substituted glycerols, 2-substituted 1, 3-propanediols and 1, 4-diols were obtained in high optical yields by the asymmetric transesterification using activated esters as acyl donors. Facile process for the kinetic resolution of racemic alcohols was developed by the lipase-catalyzed esterification with acid anhydride. And chiral 1, 4-dihydropyridines and barbiturates were obtained in high optical yields by the lipase-catalyzed hydrolysis of their acyloxymethyl groups. Chiral medicines were synthesized from optically active compounds obtained by these lipase-catalayzed asymmetric reactions.

Kinetic resolution of racemic alcohols with chiral car☐ylic acids and dicyclohexylcarbodiimide

The DCC-esterification method has been used to kinetically resolve racemic mixtures of alcohols. With simple chiral car☐ylic acids, such as O-aryl lactic acids, in the presence of various basic catalysts, mixtures of the enantiomerically enriched alcohols (e.e.<50%) and the corresponding esters (d.e.<70%) have been obtained.