Amino acids are a versatile source of chiral building blocks for organic synthesis and leveraging the intrinsic chirality of amino acids has been pivotal in the production of optically pure compounds and medicines. Our biocatalysis toolbox at Symeres has streamlined efficient access to a wide range of multifunctional and optically pure amino acids and their derivatives. Biocatalysis also enables the selective synthesis of unnatural amino acids that may not be readily available through traditional chemical synthesis methods.
For example, the enzymatic resolution of amino acid amide precursors, using aminopeptidases or amidases, has been extensively applied within Symeres 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 standard chemical hydrolysis. We have hands-on 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 is readily amenable to application 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.
In addition to our expertise in biocatalysis, we have also accumulated a wealth of knowledge in the synthesis of both natural and unnatural amino acids, utilizing Strecker and Petasis reactions for the efficient synthesis of amino acid components of complex novel substrates. Furthermore, we are experts in multistep sequences to yield intricately decorated amino acids, for example utilizing the Bucherer-Bergs reaction for the synthesis of hydantoins and their subsequent hydrolysis to yield amino acid derivatives.
In combination with our custom synthesis offerings for your specific project needs, we also have a range of complex and novel amino acid derivatives, produced using the biocatalysis toolbox at Symeres, which, can be found in the Chiralix catalog.
Below are some representative examples of amino acids available from Chiralix,
Please feel free to contact our experts directly to explore the possibilities and see how Symeres can help streamline your amino acid synthesis!
[1] R.H. Blaauw et al., Chimia 2004, 58 , 104-107 DOI: https://doi.org/10.2533/000942904777678127
