Scientists from the ZIOC have proposed an effective method for the synthesis of non-proteinogenic alpha-amino acids

Chiral alpha-amino acids play an important role in nature. Amino acids, which are part of proteins and enzymes (proteinogenic), are involved in homeostasis, gene expression, and hormone synthesis, and are also actively used as nutritional supplements and medicines for the treatment of muscle dysfunction and various forms of cancer. However, a significant number of both natural and synthetic bioactive compounds contain non-proteinogenic alpha-amino acids in their structure, such as phenylglycine, adamantylglycine, and their derivatives. The synthesis of such compounds often involves cyanation steps, which require highly toxic cyanation reagents. For this reason, the search for alternative safer ways to obtain non-proteinogenic alpha-amino acids is an important scientific task.

Scientists of the I.N. Nazarov Laboratory of Fine Organic Synthesis of the Zelinsky Institute actively conducts research aimed at developing new methods of stereoselective synthesis. In one of their latest works, they proposed a method for the asymmetric synthesis of functionally substituted allomaltol derivatives based on the enantioselective addition of N-protected aldimines to it in the presence of an organocatalyst, a bifunctional tertiary amine containing a squaric acid moiety. The enantiomeric excess in most cases exceeded 90%. Oxidative fragmentation of the resulting structures under the action of Ru (III) salts led to the production of enantiomerically enriched (> 90% ee) non-proteinogenic alpha-amino acids in high yields. It should be especially noted that the reactions are successfully scaled, which allows us to consider the developed approach as a preparative method for the asymmetric synthesis of a wide range of non-proteinogenic alpha-amino acids.
 

Source:

Ruslan A. Kovalevsky, Alexander S. Kucherenko, Sergei G. Zlotin Concise enantioselective synthesis of non-proteinogenic a-aminoacids via an organocatalytic Mannich-type reaction // Chem. Commun., 2022, 58, 12827–12830. DOI: 10.1039/d2cc04909k.