Chemoenzymatic Preparation of Enantiomerically Enriched (R)-(-)-Mandelic Acid Derivatives: Application in the Synthesis of the Active Agent Pemoline

doi:10.1002/EJOC.201700161

Paper

Chemoenzymatic Preparation of Enantiomerically Enriched (R)-(-)-Mandelic Acid Derivatives: Application in the Synthesis of the Active Agent Pemoline

Published Apr 26, 2017 · Marcin Poterała, M. Dranka, Paweł Borowiecki

European Journal of Organic Chemistry

Q2 SJR score

24

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0

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Abstract

The enantioselective resolution of several racemic derivatives of mandelic acid methyl ester catalyzed by lipases from Pseudomonas fluorescens (Amano AK) or Burkholderia cepacia (Amano PS-C II and Amano PS-IM) has been achieved. A gram-scale lipase-mediated kinetic resolution approach has been developed that allows the facile synthesis of the corresponding methyl (R)-(–)-mandelates with excellent enantiomeric excesses (up to >99 % ee) and reaction enantioselectivity (E values up to >200). The dopaminergic agent pemoline, used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy, was synthesized with 98 % ee in a straightforward route by condensing the prepared methyl (R)-(–)-mandelate with guanidine hydrochloride under basic conditions. The desired (R)-(+)-pemoline in optically pure form (>99 % ee) was obtained after two recrystallizations from ethanol. However, it was confirmed by chiral HPLC that optically active pemoline undergoes racemization in methanol solution.

Study Snapshot

This study developed a gram-scale lipase-mediated kinetic resolution approach for the facile synthesis of enantiomerically rich (R)-(-)-mandelic acid derivatives, which can be used to synthesize the dopaminergic agent pemoline for treating ADHD and n

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Chemoenzymatic Preparation of Enantiomerically Enriched (R)-(-)-Mandelic Acid Derivatives: Application in the Synthesis of the Active Agent Pemoline

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References

Citations

Fungal Biocatalysis in Stereoselective Oxidation of 2-Phenylethanol

Fungal biocatalysis using Beauveria bassiana, Rhizopus arrhizus DSM 1185, and Rhizopus brongniartii DSM 6651 can produce chiral building blocks, including 1-phenylethane-1,2-diol and t

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Cobalt catalysts enable chemo- and regioselective hydroxylation of arylacetic acid equivalents, leading to mandelic acid derivatives under mild conditions and wide synthetic practicality.

A Dual Ni/Photoredox Cross-Coupling Approach toward Mandelic Acids.

This study presents a novel reductive Ni/photoredox cross-coupling method for preparing unprotected mandelic acid ester derivatives using readily accessible N-alkoxyphthalimides and aryl halides.

Enantiospecific Analysis of Carboxylic Acids Using Cinchona Alkaloid Dimers as Chiral Solvating Agents.

Cinchona alkaloid dimer (DHQ)2PHAL effectively serves as a chiral solvating agent for enantiospecific analysis of carboxylic acids through 1H NMR spectroscopy.

Synthesis and enzymatic resolution of novel analogs of alicyclic and heterocyclic mandelic acid derivatives

This study demonstrates the synthesis and enzymatic resolution of novel alicyclic and heterocyclic mandelic acid derivatives using commercially available aldehydes and the Amano PS enzyme.