Hydrolase-catalyzed kinetic resolutions of chiral alcohols: Mechanistic study on the origin of the enantioselectivity

Tadashi Ema, Takashi Sakai

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2 Citations (Scopus)

Abstract

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 lipase-catalyzed transesterifications of chiral alcohols in organic solvents can proceed even at -40°C. Interestingly, the E value increased with decreasing temperature, and a linear relationship was observed between 1n 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.

Original languageEnglish
Pages (from-to)691-698
Number of pages8
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume58
Issue number7
Publication statusPublished - Jul 2000

Fingerprint

Enantioselectivity
Hydrolases
Alcohols
Lipase
Kinetics
Subtilisins
Orbital calculations
Transesterification
Molecular orbitals
Organic solvents
Crystal structure
Thermodynamics
X rays
Substrates

Keywords

  • Biocatalysis
  • Chiral discrimination
  • Chiral recognition
  • Enantioselectivity
  • Enzyme
  • Lipase
  • Low-temperature method
  • Optically active alcohol
  • Subtilisin
  • Transition state

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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abstract = "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 lipase-catalyzed transesterifications of chiral alcohols in organic solvents can proceed even at -40°C. Interestingly, the E value increased with decreasing temperature, and a linear relationship was observed between 1n 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.",
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AU - Ema, Tadashi

AU - Sakai, Takashi

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N2 - 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 lipase-catalyzed transesterifications of chiral alcohols in organic solvents can proceed even at -40°C. Interestingly, the E value increased with decreasing temperature, and a linear relationship was observed between 1n 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.

AB - 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 lipase-catalyzed transesterifications of chiral alcohols in organic solvents can proceed even at -40°C. Interestingly, the E value increased with decreasing temperature, and a linear relationship was observed between 1n 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.

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