ChiPros Chiral Acids

By: Daniel Weibel, Chemfiles Volume 11 Article 1

Enantiopure α- and ß-hydroxy acids and esters are versatile building blocks for the preparation of a wide range of active pharmaceutical ingredients by incorporating them as esters, amides or ethers, or after further derivatization, as diols, amino alcohols, thioethers.

Hydroxy acids are accessible via a range of biotransformations, among them are the stereoselective hydrolysis of the racemic ester precursor or reduction of the corresponding keto esters. Hydroxynitrile lyase (HNL) processes catalyze the stereoselective addition of HCN to aldehydes and ketones yielding single-enantiomeric nitriles.1 Application of nitrilases or a combination of nitrile-hydratase plus amidase allows the transformation of the starting material into the desired enantiomer of the corresponding acid in a dynamic kinetic resolution fi nally yielding mandelic acid derivatives.

BASF developed proprietary processes based on dehydrogenases to off er access to a wide range of α- and ß-hydroxy esters, starting from readily available keto esters. Due to the large range of enzymes available, both enantiomers can normally be made. Another established technology is enzymatic resolution using lipases which only acylate one enantiomer.

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Materials

     

References

  1. Breuer, M.; Ditrich, K. et al. Angew. Chem. Int. Ed. 2004, 43, 788-824.

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