Amino acids are a versatile source of chiral building blocks for synthesis. The biocatalysis toolbox at Symeres enables efficient access to a wide range of multifunctional, optically pure, unnatural amino acids and their derivatives. For example, the enzymatic resolution of amino acid amide precursors, using aminopeptidases or amidases, has been extensively applied to produce densely functionalized amino acids[1].
After resolution, the l-amino acid formed can be separated from the remaining d-amide by an extractive workup procedure. In a subsequent step, the d-amide is further hydrolyzed to give the d-acid, either by another biocatalytic step, in the case of sensitive substrates, or by chemical hydrolysis. We have experience of this approach with a broad range of substrates, providing many functional handles on the amino acid side chain. Furthermore, this approach gives access to both l- and d-amino acids and can be applied on a large scale.
The amino acids can be α-H or α,α-disubstituted and the biocatalysts are very stereospecific to yield the products in high optical purity. A compelling example of the discriminatory power of the biocatalysts is found in the stereospecific hydrolysis of α-methyl-α-trifluoromethylglycinamide. The amidase used is able to distinguish perfectly between two sterically very similar substituents, stopping at exactly 50% conversion and giving both the (R)-acid and the (S)-amide with very high enantiomeric excess.
As well as offering this approach for your specific project needs, some representative examples of amino acids produced using the biocatalysis toolbox at Symeres can be found in the Chiralix catalog. Please contact us to explore the possibilities!
Please contact us to explore the possibilities!
[1] Blaauw, R., IJzendoorn, D. et. al., Chemo-Enzymatic Synthesis of Chiral Fluorine-Containing Building Blocks, Chimia 58, 2004 104 - 107 Link
