NOBF₄-Mediated Assembly of the Sydnone Imine Scaffold in the Synthesis of Double Nitric Oxide Donors

Abstract

A direct approach toward the construction of furoxan-sydnone imine double NO-donors involving the NOBF₄-mediated nitrosation–cyclization sequence of α-amino nitriles as a key synthetic step was developed. The described protocol excludes the isolation of carcinogenic N-nitrosamines, operates broad substrate scope, and enables the preparation of fully substituted sydnone imines linked to the furoxan ring via different linkers or directly through C–C bond. Synthesized library of furoxan-sydnone imine hybrids demonstrated a promising ability to release NO in a wide range of concentrations which is useful for various biomedical insights.

Key words

nitric oxide - cyclization - nitrogen heterocycles - mesoionic heterocycles - molecular hybridization

Publication History

Received: 08 December 2022

Accepted after revision: 12 January 2023

Accepted Manuscript online:
12 January 2023

Article published online:
14 February 2023

• References

• 1a Vanhoutte PM, Zhao Y, Xu A, Leung SW. S. Circ. Res. 2016; 119: 375
• 1b Yang Y, Huang Z, Li L.-L. Nanoscale 2021; 13: 444
• 2 Paulo M, Costa DE. F. R, Bonaventura D, Lunardi CN, Bendhack LM. Curr. Pharm. Des. 2020; 26: 3748
• 3 Gkaliagkousi E, Ritter J, Ferro A. Circ. Res. 2007; 101: 654
• 4 Krol M, Kepinska M. Int. J. Mol. Sci. 2021; 22: 56
• 5a Serafim RA. M, Pernichelle FG, Ferreira EI. Expert Opin. Drug Discov. 2017; 12: 941
• 5b Bryan NS. Isr. J. Chem. 2019; 59: 414
• 5c Huang Z, Fu J, Zhang Y. J. Med. Chem. 2017; 60: 7617
• 6 Bath PM. W, Krishnan K, Appleton JP. Cochrane Database Syst. Rev. 2017; 4: CD000398
• 7a Wang PG, Xian M, Tang X, Wu X, Wen Z, Cai T, Janczuk AJ. Chem. Rev. 2002; 102: 1091
• 7b Gasco A, Schönafinger K. In Nitric Oxide Donors: For Pharmaceutical and Biological Applications . Wang PG, Cai TB, Taniguchi N. Wiley-VCH; Weinheim: 2005: 131
• 7c Schönafinger K. Pharmaco 1999; 54: 316

For recent reviews on furoxans and/or sydnone imines, see:
• 8a Fershtat LL, Zhilin ES. Molecules 2021; 26: 5705
• 8b Makhova NN, Fershtat LL. In Comprehensive Heterocyclic Chemistry IV, Vol. 5. Black D, Cossy J, Stevens CV. Elsevier; Amsterdam: 2022: 190
• 8c Fershtat LL, Teslenko FE. Synthesis 2021; 53: 3673
• 8d Makhova NN, Fershtat LL. Tetrahedron Lett. 2018; 59: 2317
• 8e Fershtat LL, Makhova NN. ChemMedChem 2017; 12: 622
• 8f Fershtat LL, Makhova NN. Russ. Chem. Rev. 2016; 85: 1097
• 8g Makhova NN, Belen’kii LI, Gazieva GA, Dalinger IL, Konstantinova LS, Kuznetsov VV, Kravchenko AN, Krayushkin MM, Rakitin OA, Starosotnikov AM, Fershtat LL, Shevelev SA, Shirinian VZ, Yarovenko VN. Russ. Chem. Rev. 2020; 89: 55
• 8h Cherepanov IA, Moiseev SK. Adv. Heterocycl. Chem. 2020; 131: 49
• 9 Bohn H, Brendel J, Martorana PA, Schönafinger K. Br. J. Pharmacol. 1995; 114: 1605
• 10 Ustyuzhanina NE, Fershtat LL, Gening ML, Nifantiev NE, Makhova NN. Mendeleev Commun. 2018; 28: 49
• 11 Balbo S, Lazzarato L, di Stilo A, Fruttero R, Lombaert N, Kirsch-Volders M. Toxicol. Lett. 2008; 178: 44
• 12a Khmel’nitskaya EY, Levina VI, Trukhacheva LA, Grigoriev NB, Kalinin VN, Cherepanov IA, Lebedev SN, Granik VG. Russ. Chem. Bull., Int. Ed. 2004; 53: 2840
• 12b Kikuchi K, Hirata M, Nagaoka A. Jpn. J. Pharmacol. 1970; 20: 102
• 12c Drummer C, Valta-Seufzer U, Karrenbrock B, Heim JM, Gerzer R. Eur. Heart J. 1991; 12: 541
• 13 For a recent review on biorthogonal reactions of mesoionic heterocycles, see: Porte K, Riomet M, Figliola C, Audisio D, Taran F. Chem. Rev. 2021; 121: 6718

For recent examples, see:
• 14a Bernard S, Audisio D, Riomet M, Bregant S, Sallustrau A, Plougastel L, Decuypere E, Gabillet S, Kumar RA, Elyian J, Trinh MN, Koniev O, Wagner A, Kolodych S, Taran F. Angew. Chem. Int. Ed. 2017; 56: 15612
• 14b Shao Z, Liu W, Tao H, Liu F, Zeng R, Champagne PA, Cao Y, Houk KN, Liang Y. Chem. Commun. 2018; 54: 14089
• 14c Riomet M, Decuypere E, Porte K, Bernard S, Plougastel L, Kolodych S, Audisio D, Taran F. Chem. Eur. J. 2018; 24: 8535
• 14d Riomet M, Porte K, Madegard L, Thuéry P, Audisio D, Taran F. Org. Lett. 2020; 22: 2403
• 14e Riomet M, Porte K, Wijkhuisen A, Audisio D, Taran F. Chem. Commun. 2020; 56: 7183
• 14f Porte K, Renoux B, Péraudeau E, Clarhaut J, Eddhif B, Poinot P, Gravel E, Doris E, Wijkhuisen A, Audisio D, Papot S, Taran F. Angew. Chem. Int. Ed. 2019; 58: 6366
• 15a Zhilin ES, Ustyuzhanina NE, Fershtat LL, Nifantiev NE, Makhova NN. Chem. Biol. Drug Des. 2022; 100: 1017
• 15b Zhilin ES, Bystrov DM, Ananyev IV, Fershtat LL, Makhova NN. Chem. Eur. J. 2019; 25: 14284
• 16a Kulikov AS, Epishina MA, Zhilin ES, Shuvaev AD, Fershtat LL, Makhova NN. Mendeleev Commun. 2021; 31: 42
• 16b Kots AYa, Grafov MA, Khropov YuV, Betin VL, Belushkina NN, Busygina OG, Yazykova MYu, Ovchinnikov IV, Kulikov AS, Makhova NN, Medvedeva NA, Bulargina TV, Severina IS. Br. J. Pharmacol. 2000; 129: 1163
• 17a Beal EN, Turnbull K. Synth. Commun. 1992; 22: 673
• 17b Daeniker HU, Druey J. Helv. Chim. Acta 1962; 45: 2426
• 18 Fast decomposition of oxalic acid and oxalates upon treatment with acetic anhydride was previously reported: Whitford EL. J. Am. Chem. Soc. 1925; 47: 2934
• 19a Masuda K, Imashiro Y, Kaneko T. Chem. Pharm. Bull. 1970; 18: 128
• 19b Soulere L, Bringaud F, Hoffmann P. J. Heterocycl. Chem. 2003; 40: 943
• 20 Sorba G, Ermondi G, Fruttero R, Galli U, Gasco A. J. Heterocycl. Chem. 1996; 33: 327
• 21 Boschi D, Di Stilo A, Cena C, Lolli M, Fruttero R, Gasco A. Pharm. Res. 1997; 14: 1750
• 22 CrysAlisPro. Version 1.171.41.106a . Rigaku Oxford Diffraction; Japan: 2021
• 23 Sheldrick GM. Acta Crystallogr., Sect. A 2015; 71: 3
• 24 Sheldrick GM. Acta Crystallogr., Sect. C 2015; 71: 3
• 25 Dolomanov OV, Bourhis LJ, Gildea RJ, Howard JA. K, Puschmann H. J. Appl. Cryst. 2009; 42: 229
• 26 Macrae CF, Edgington PR, McCabe P, Pidcock E, Shields GP, Taylor R, Towler M, van de Streek J. J. Appl. Cryst. 2006; 39: 453
• 27 CCDC 2220994 (5a) and 2220995 (11) contain the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures