- Tailoring Lipase Specificity by Solvent and Substrate Chemistries
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An acyl binding structural model has been developed to explain the observed catalytic efficiencies and enantioselectivities of Candida rugosa lipase-catalyzed (trans)esterification reactions involving 2-hydroxy acids and vinyl esters, respectively, and acylation reactions involving both cyclic and acyclic alcohols.A clear minimum was observed for (trans)esterification of six-carbon acyl moieties.Moreover, the stereoselectivity of 2-hydroxy acid esterification in a number of hydrophilic and hydrophobic solvents was dependent on the acyl chain length: S-isomers of 2-hydroxy acids were acylated for acyl chain lengths of six or fewer, whereas the R-isomers were preferentially esterified for acyl chain lengths of eight or more.These results suggest that CRL contains both large and small acyl binding regions or pockets with high catalysis observed for proper fitting substrates into either pocket.CRL is also highly selective and reactive on secondary cyclic alcohols.In particular, the R isomers of menthol and sec-phenethanol are acylated efficiently by straight-chain vinyl esters.The catalytic efficiency of acylation (i.e., Vmax/Km for the secondary alcohol) is strongly dependent on the acyl chain length.Once again, a clear minimum is observed with vinyl caproate (C6) as acyl donor.This phenomenon may reflect the greater degree of steric hinderance in the acyl enzyme intermediate caused by the caproate group.A mechanistic and thermodynamic rationale was proposed for the effects of solvent and substrate chemistries on CRL catalysis on organic solvents.
- Parida, Sanghamitra,Dordick, Jonathan S.
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- Method for Improving Optical Purity of 2-Hydroxycarboxylic Acid or Derivative Thereof
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To provide a method for improving optical purity of an optically active 2-hydroxycarboxylic acid or a derivative thereof, which is useful as a raw material in the manufacture of medicines, agrochemicais, and industrial products. The method of the invention for improving purity of a hydroxycarboxylic acid of the following formula (1a) or (1b) or a derivative thereof includes the steps of reacting the hydroxycarboxylic acid of the following formula (1a) or (1b) with at least one optically inactive base selected from the group consisting of an alkali metal, alkoxide and a secondary amine in the presence of a solvent and, subsequently, performing recrystallization, to thereby form a hydroxycarboxylic acid salt of the following formula (IIIa) or (IIIb): wherein R1 represents a C1-8 alkyl group, and R2 represents an alkali metal or a secondary amine.
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Paragraph 0090
(2016/04/20)
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- Novel synthesis of butyl (S)-2-hydroxybutanoate, the key intermediate of PPARα agonist (R)-K-13675 from butyl (2 S,3 R)-epoxybutanoate and butyl (S)-2,3-epoxypropanoate
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Novel synthetic methods for the production of butyl (S)-2-hydroxybutanoate starting from butyl (2S,3R)-epoxybutanoate or butyl (S)-2,3-epoxypropanoate were established. The former method utilized the regioselective thiolysis of the epoxybutanoate mediated by scandium triflate and subsequent reductive cleavage of the thioether to give butyl (S)-2-hydroxybutanoate with stereochemical retention in quantitative yield. The latter method utilized one-step conversion by a combination of methylmagnesium bromide and copper catalyst in high yield. Georg Thieme Verlag Stuttgart, New York.
- Araki, Takaaki,Koura, Minoru,Yamazaki, Yukiyoshi,Shibuya, Kimiyuki
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p. 1319 - 1324
(2013/06/27)
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- PROCESS FOR PRODUCING OPTICALLY ACTIVE 2-HYDROXYBUTYRIC ESTER
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To provide a process for producing an optically active 2-hydroxybutyric ester at high yield and high optical purity. The process for producing an optically active 2-hydroxybutyric ester (1), characterized in that the process includes reacting an optically
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Page/Page column 6; 7
(2008/06/13)
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- A practical synthesis of the PPARα agonist, (R)-K-13675, starting from (S)-2-hydroxybutyrolactone
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A practical synthesis of optically pure PPARα agonist, (R)-K-13675, is described. This process is based on the use of (S)-2-hydroxybutyrolactone, which can be transformed into the requisite n-butyl (S)-2-hydroxybutanoate in an efficient manner. A key reaction is the etherification between the phenol and n-butyl (S)-2-trifluoromethanesulfonyloxybutanoate to give the phenyl ether in excellent yield without loss of optical purity.
- Yamazaki, Yukiyoshi,Araki, Takaaki,Koura, Minoru,Shibuya, Kimiyuki
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p. 8155 - 8158
(2008/12/21)
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- PROCESS FOR PRODUCING OPTICALLY ACTIVE ESTER
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A process for producing an optically active 2-hydroxybutyric ester (1), characterized by reacting an optically active 2,3-epoxybutyric ester (2) with a thiol compound in the presence of scandium trifluoromethanesulfonate or ytterbium trifluoromethanesulfo
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Page/Page column 11
(2008/06/13)
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- Substrate Structure and Solvent Hydrophobicity Control Lipase Catalysis and Enantioselectivity in Organic Media
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The lipase from Candida cylindracea catalyzes the enantioselective esterification of 2-hydroxy acids in nearly anhydrous organic solvents with primary alcohols as nucleophiles. The nature of the 2-hydroxy acid and organic reaction medium affects the efficiency of catalysis and the enantioselectivity. Straight-chain 2-hydroxy acids are highly reactive and give nearly 100% enantioselectivities in esterification reactions with 1-butanol. Slight branching with a methyl group adjacent to the 2-hydroxy moiety in toluene causes a substantial loss (up to 200-fold) in the lipase's catalytic efficiency with a concomitant loss in enantioselectivity. Losses in catalytic efficiency and enantioselectivity are also observed when the lipase is employed in hydrophilic organic media such as dioxane or tetrahydrofuran as compared to hydrophobic solvents such as toluene. With straight-chain substrates, the lipase is over 100-fold more active in toluene than in tetrahydrofuran or dioxane, while optimal enantioselectivity is observed in toluene. The loss in enantioselectivity in hydrophilic solvents is mainly due to a drop in the catalytic efficiencies of the S isomers, as the R isomers' catalytic efficiencies remain largely unchanged. In highly apolar solvents, such as cyclohexane, enantioselective relaxation occurs due to an increase in the reactivity of the R isomers relative to that of their S counterparts. These findings enabled a rational selection of substrates and solvents for a two-step, chemoenzymatic synthesis of optically active 1,2-diols to be carried out, the first step being the aforementioned enantioselective esterification of 2-hydroxy acids followed by reduction with LiAl(OCH3)3H to give the optically active 1,2-diol. Diols such as (S)-(+)-1,2-propanediol, (S)-(-)-1,2-butanediol, (S)-(-)-1,2-hexanediol, and (S)-(-)-4-methyl-1,2-pentanediol were produced in high optical purities (at least 98% enantiomeric excess (ee)).
- Parida, Sanghamitra,Dordick, Jonathan S.
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p. 2253 - 2259
(2007/10/02)
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