A new approach has been developed for synthesizing important compounds with potential biological activity − enantiomerically pure 3-heteryl-2-methylpropanoic and 3-heterylbutanoic acids. The kinetic dynamic enzymatic resolution methodology was applied at key synthesis stages. A dual biocatalytic purification method was employed to achieve a high degree of optical purity of the obtained products. The resulting amines are promising building blocks for the development and production of new pharmaceuticals and biologically active compounds.
[1] Shchekotikhin, A. (2020). Heterocyclic Compounds in Medicinal Chemistry. Chemistry of Heterocyclic Compounds, 56, 625. DOI: 10.1007/s10593-020-02711-7
[2] Gomtsyan, A. (2012). Heterocycles in drugs and drug discovery. Chemistry of Heterocyclic Compounds, 48, 7–10. DOI: 10.1007/s10593-012-0960-z
[3] Luo, L., Yao, J.-P., Yang, L., Feng, Ch.-L., Tang, W., Wang, G.-F., Zuo, J.-P., & Lu, W. (2010). Design and synthesis of novel benzimidazole derivatives as inhibitors of hepatitis B virus. Bioorganic & Medicinal Chemistry, 18(14), 5048–5055. DOI: 10.1016/j.bmc.2010.05.076
[4] Hallinan, E. A., Hagen, T. J., Tsymbalov, S., & Husa, R. K., Lee, A. C. (1996). Aminoacetyl Moiety as a Potential Surrogate for Diacylhydrazine Group of SC-51089, a Potent PGE2 Antagonist, and Its Analogs. Journal of Medicinal Chemistry, 39(2), 609–613. DOI: 10.1021/jm950454k
[5] Leschke, Ch., Elz, S., Garbarg, l. M., & Schunack, W. (1995). Synthesis and Histamine H1 Receptor Agonist Activity of a Series of 2-Phenylhistamines, 2-Heteroarylhistamines, and Analogues. Journal of Medicinal Chemistry, 38(8), 1287–1294. DOI: 10.1021/jm00008a007
[6] Miyatake, K., Yoshio, T., Ayako, Y., Hidenori, O., Shinya, O., Kohji, K., Kazuo, H. T., Takeda, S., Akamatsu, H., Itoh, H., Misumi, K., Inoue, S., & Takag, T. (2008). Bioorganic and Medicinal Chemistry, 16(5), 2261–2275. DOI: 10.1016/j.bmc.2007.11.074
[7] Hack, S., Wörlein, B., Höfner, G., Pabel, J., & Wanner, K. T. (2011). Development of imidazole alkanoic acids as mGAT3 selective GABA uptake inhibitors. European Journal of Medicinal Chemistry, 46(5), 1483–1498. DOI: 10.1016/j.ejmech.2011.01.042
[8] Ghorai, P., Kraus, A., Keller, M., Götte, C., Igel, P., Schneider, E., Schnell, D., Bernhardt, G., Dove, S., Elz, S., Seifert, R., & Buschauer, A. (2008). Acylguanidines as Bioisosteres of Guanidines: NG-Acylated Imidazolylpropylguanidines, a New Class of Histamine H2 Receptor Agonists. Journal of Medicinal Chemistry, 51(22), 7193–7204. DOI: 10.1021/jm800841w
[9] U.S. Food and Drug Administration. (1992). Development of New Stereoisomeric Drugs. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-new-stereoisomeric-drugs
[10] European Medicines Agency. (1993). Investigation of Chiral Active Substances. https://www.ema.europa.eu/en/documents/scientific-guideline/investigation-chiral-active-substances_en.pdf
[11] Calcaterra, A. D., & Acquarica, I. (2018). The market of chiral drugs: Chiral switches versus de novo enantiomerically pure compounds. Journal of Pharmaceutical and Biomedical Analysis, 147, 323–340. DOI: 10.1016/j.jpba.2017.07.008
[12] Caner, H., Groner, E., & Levy, L. (2004). Trends in the development of chiral drugs. Drug Discovery Today, 9, 105–110. DOI: 10.1016/S1359-6446(03)02904-0
[13] Zhong, H., Shevlin, M., & Chirik, P. J. (2020). Cobalt-Catalyzed Asymmetric Hydrogenation of α,β-Unsaturated Carboxylic Acids by Homolytic H₂ Cleavage. Journal of the American Chemical Society, 142(11), 5272–5281. DOI: 10.1021/jacs.9b13876
[14] Aycock, R. A., Wang, H., & Jui, N. T. (2017). A mild catalytic system for radical conjugate addition of nitrogen heterocycles. Chemical Science, 8(4), 3121–3125. DOI: 10.1039/C7SC00243B
[15] Kolodiazhnyi, O. I., Kolodiazhna, A. O., Faiziiev, O., & Gurova, Y. (2024). Enzymatic Deracemization of Fluorinated Arylcarboxylic Acids: Chiral Enzymatic Analysis and Absolute Stereochemistry Using Chiral HPLC. Symmetry, 16(9), 1150. DOI: 10.3390/sym16091150
[16] Kolodiazhna, А. О., Faiziiev, О. О., & Kolodiazhnyi, О. І. (2023). Fermentative Kinetic Deracemization of Fluorinated 3-Arylalkanoic Acids. Доповіді НАН України, 5, 37–46. DOI: 10.15407/dopovidi2023.05.037
[17] Kolodiazhna, А. О., & Faiziiev, О. О. (2023). Fluorine-Containing 3-Arylalkanoic Acids. In A. I. Vovk (Ed.), Bioaktyvni spoluky, novi rechovyny i materialy (pp. 66–72). Interservis.