Enzymatic resolution of hindered cyanohydrins, key precursors of muscarinic receptor antagonists

Recuero, Verónica; Ferrero, Miguel; Gotor‐Fernández, Vicente; Brieva, Rosario; Gotor, Vicente

doi:10.1016/j.tetasy.2007.04.002

Cited by 18 publications

(8 citation statements)

References 28 publications

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“…Oxybutynin (4-(diethylamino)but-2-ynyl(RS)-2-cyclohexyl-2-hydroxy-2-phenylacetate, OBN) has been widely prescribed for the treatment of urinary tract disorders [12]. Separation of OBN enantiomers by high performance liquid chromalography (HPLC) with HP-β-CD as chiral mobile phase additive was investigated [13].…”

Section: Introductionmentioning

confidence: 99%

Inclusion behavior of oxybutynin with hydroxypropyl-β-cyclodextrin

Zhang

Pan

Tang

et al. 2011

J. Cent. South Univ. Technol.

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Inclusion behavior of oxybutynin (OBN) with hydroxypropyl-β-cyclodextrin (HP-β-CD) was investigated by ultraviolet absorption spectrum and fluorescence spectrum. A reliable determination of the complex stoichiometry was provided by the continuous variation technique. Alcohol was added to further investigate the mechanism of the inclusion behavior. Thermodynamic constants ΔG, ΔH and ΔS for inclusion interaction of OBN and HP-β-CD were determined. The results show that host-guest complex with molar ratio of ‫1׃1‬ is formed, and inclusion stability constant between OBN and HP-β-CD is 54.9 L/mol determined by ultraviolet spectrum and 11.1 L/mol determined by fluorescence spectrum. OBN has weak binding ability with HP-β-CD in aqueous solution (stability constant <10 2 L/mol) and addition of alcohol leads to a decrease of stability constant, which indicates that the hydrophobic force contributes to the inclusion process. ΔG, ΔH and ΔS are all less than zero, which indicates that the inclusion process is a spontaneous and exothermic process.

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Section: Introductionmentioning

confidence: 99%

Inclusion behavior of oxybutynin with hydroxypropyl-β-cyclodextrin

Zhang

Pan

Tang

et al. 2011

J. Cent. South Univ. Technol.

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“…The synthesis of 11 via bisulfite adduct formation and treatment with NaCN at best gave only a 1:4 mixture of β-keto ester 9 and cyanohydrin 11 . Derivatisation of this crude mixture with SOCl 2 /NEt 3 or MsCl/NEt 3 led to the corresponding product 12a or 12b , respectively, via cyanide elimination (identified by GC–MS) (Scheme ), and it was apparent that NEt 3 gave cyanide elimination prior to derivatisation.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Several Routes to Advanced Pregabalin Intermediates: Synthesis and Enantioselective Enzymatic Reduction Using Ene-Reductases

Debarge

McDaid

O'Neill

et al. 2014

Org. Process Res. Dev.

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“…A large number of drugs are chiral compounds whose biological activity relies largely on the configuration of their stereocenter, where the microscopic chemical environment is a key factor The chiral environment is one that contains chiral elements, such as chiral reagents, chiral catalysts and chiral solvents, whereas the achiral environment means no chiral factors. Generally, the two enantiomers of a chiral molecule have the same properties in an achiral environment, for example, boiling point, melting point, solubility and reaction rate.…”

Section: Introductionmentioning

confidence: 99%

Simulation and optimization of Novozym 40086 kinetic resolution of α‐cyclopentylphenylacetic acid enantiomers

Zhang

Cheng

et al. 2019

J of Chemical Tech & Biotech

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BACKGROUND: Enzymatic resolution of enantiomers by hydrolysis is a popular method, yet most enantiomers have low solubility in the aqueous phase, resulting in low conversion. Notwithstanding this, the simulation and optimization of the reaction process by modelling has been reported only rarely. Thus, PEG was added to the aqueous phase and a mathematical model was established to obtain optimal conditions. RESULTS: The effects of various parameters were investigated to build an optimized reaction system. The results indicated that temperature and pH had little effect on enantiomeric excess, but they had significant effect on conversion. Conversion was enhanced by 85% with the addition of PEG 400. Kinetic studies showed that pentanol competitively inhibited enzyme activity. A mathematical model was developed, and forward and reverse reactions were taken into consideration. Through simulation and optimization of model, the optimum conditions were obtained as follows: 10 mg mL −1 Novozym 40086, 10 mmol L −1 substrate, 30% PEG 400, temperature 45 ∘ C, pH 6.5 and reaction time 36 h. CONCLUSION: Chiral resolution of -cyclopentylphenylacetic acid enantiomer (CPPA) was achieved by Novozym 40086 enantioselective hydrolysis of the CPPA ester. Under optimum conditions, ee p and c s were 95.83% and 88.52%, respectively. The relative errors between predicted values and experimental values were <5%, confirming that the model could accurately predict the enzymatic resolution reaction.

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Enzymatic resolution of hindered cyanohydrins, key precursors of muscarinic receptor antagonists

Cited by 18 publications

References 28 publications

Inclusion behavior of oxybutynin with hydroxypropyl-β-cyclodextrin

Inclusion behavior of oxybutynin with hydroxypropyl-β-cyclodextrin

Evaluation of Several Routes to Advanced Pregabalin Intermediates: Synthesis and Enantioselective Enzymatic Reduction Using Ene-Reductases

Simulation and optimization of Novozym 40086 kinetic resolution of α‐cyclopentylphenylacetic acid enantiomers

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