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Detail publikace

Autor: Králová, P.; Maloň, M.; Volná, T.; Ručilová, V.; Soural, M.
Název práce v češtině: Stereoselektivní syntéza derivátů morfolin a thiomorfolin-3-karboxylových kyselin pomocí syntézy na pevné fázi
Název práce v angličtině: Stereoselective Polymer-Supported Synthesis of Morpholine and Thiomorpholine-3-carboxylic Acid Derivatives
Klíčová slova v češtině: morfoline, thiomorfoline, stereoselektivní syntéza, syntéza na pevné fázi
Klíčová slova v angličtině:morpholine, thiomorpholine, stereoselective synthesis, solid-phase synthesis
Abstrakt česky: Derivatives of morpholine and thiomorpholine bearing the carbonyl group in the C3 position have been studied in medicinal chemistry as potential inhibitors of tumor necrosis factor-alpha converting enzyme (TACE), [1,2] as agonists of the very late antigen (VLA-4) (for derivatives with Y = SO2) [3] and as drugs for the potential treatment of neurodegenerative diseases. [4] In this context, we developed a general method applicable for the preparation of desired N-sulfonyl derivatives (Y = SO2) and N-acyl derivatives (Y = CO). Using solid-phase synthesis, diverse derivatives can be easily obtained by simply changing the building blocks and reagents. The stereoselective reduction of the C5-6 double bound was performed using triethylsilane. [5]

[1] J. I. Levin, J. M. Chen, L. M. Laakso, M. Du, X. Du, A. M. Venkatesan, V. Sandanayaka, A. Zask, J. Xu, W. Xu, Y. Zhang and J. S. Skotnicki, Med. Chem. Lett., 2005, 15 (19), 4345.
[2] L. S.Chupak, M. A.Letavic, and K. F. McClure, WO 2000009492 A1, Feb 24, 2000.
[3] M. J. Bury, M.Cheung, H. S. Eidam and R. M. Fox, WO 2009146182 A1, Dec 3, 2009.
[4] A. Nie, J. Xiao, L. Wang, G. Liao and H. Liu, Sci. China Ser. B, Chem., 2007, 50 (3), 405.
[5] P. Králová, V. Fülöpová, M. Maloň, T. Volná, I. Popa and M. Soural, ACS Comb. Sci., 2017, 19 (3), 173.
Abstrakt anglicky: Derivatives of morpholine and thiomorpholine bearing the carbonyl group in the C3 position have been studied in medicinal chemistry as potential inhibitors of tumor necrosis factor-alpha converting enzyme (TACE), [1,2] as agonists of the very late antigen (VLA-4) (for derivatives with Y = SO2) [3] and as drugs for the potential treatment of neurodegenerative diseases. [4] In this context, we developed a general method applicable for the preparation of desired N-sulfonyl derivatives (Y = SO2) and N-acyl derivatives (Y = CO). Using solid-phase synthesis, diverse derivatives can be easily obtained by simply changing the building blocks and reagents. The stereoselective reduction of the C5-6 double bound was performed using triethylsilane. [5]

[1] J. I. Levin, J. M. Chen, L. M. Laakso, M. Du, X. Du, A. M. Venkatesan, V. Sandanayaka, A. Zask, J. Xu, W. Xu, Y. Zhang and J. S. Skotnicki, Med. Chem. Lett., 2005, 15 (19), 4345.
[2] L. S.Chupak, M. A.Letavic, and K. F. McClure, WO 2000009492 A1, Feb 24, 2000.
[3] M. J. Bury, M.Cheung, H. S. Eidam and R. M. Fox, WO 2009146182 A1, Dec 3, 2009.
[4] A. Nie, J. Xiao, L. Wang, G. Liao and H. Liu, Sci. China Ser. B, Chem., 2007, 50 (3), 405.
[5] P. Králová, V. Fülöpová, M. Maloň, T. Volná, I. Popa and M. Soural, ACS Comb. Sci., 2017, 19 (3), 173.
Jazyk v originále: angličtina
Publikace abstraktu: sborník 88/150
Forma prezentace: poster
Název konference: Blue Danube Symposium of Heterocyclic Chemistry
Místo konání: Linz (Rakousko)
Datum konání: august 30 – september 2
Rok konání: 2017
Způsob financování: TE02000058, LO1304, IGA_PrF_2017_009 and IGA_LF_2017_028