Green One-Pot Asymmetric Synthesis of Peptidomimetics via Sequential Organocatalyzed Aziridination and Passerini Multicomponent Reaction

Abstract

Peptidomimetics containing an aziridine moiety have been reported as potent cysteine protease inhibitors. In this sense, the development of stereoselective and sustainable synthetic strategies to obtain three-membered N-heterocyclic compounds has gained importance in the last decades. In this work, an efficient method was designed to achieve highly functionalized aziridine peptidomimetics via a sequential reaction, which involves the organocatalytic aziridination of α,β-unsaturated aldehydes followed by the Passerini multicomponent reaction in an environmentally friendly solvent mixture (ethanol: water).

Key words

peptidomimetics - green chemistry - organocatalysis - aziridine - multicomponent reaction

• References

• 1 Aziridines and Epoxides in Organic Synthesis. Yudin AK. Weinheim; Wiley-VCH: 2006
• 2 Paz MM, Zhang X, Lu J, Holmgren AA. Chem. Res. Toxicol. 2012; 25: 1502
• 3 Corre C, Lowden PA. S. Chem. Commun. 2004; 8: 990
• 4 Nakao Y, Fujita M, Warabi K, Matsunaga S, Fusetani N. J. Am. Chem. Soc. 2000; 122: 10462
• 5 Schulz F, Gelhaus C, Degel B, Vicik R, Heppner S, Breuning A, Leippe M, Gut J, Rosenthal PJ, Schirmeister T. ChemMedChem 2007; 2: 1214
• 6a Singh GS, Sudheesh S, Keroletswe N. ARKIVOC 2018; (i): 50
• 6b Wang C. Synthesis 2017; 49: 5307
• 6c Mao H, Jeong H, Yang J, Ha HJ, Yang JW. Chem. Eur. J. 2018; 24: 2370
• 6d Glowacka IE, Trocha A, Wroblewski AE, Piotrowska DG. Beilstein J. Org. Chem. 2019; 15: 1722
• 7a Lapinsky DJ. Three-Membered Ring Systems . In Progress in Heterocyclic Chemistry, Vol. 27. Gribble GW, Joule JA. Elsevier; Amsterdam: 2015: 61
• 7b Rotstein BH, Zaretsky S, Rai V, Yudin AK. Chem. Rev. 2014; 114: 8323
• 7c Meninno S, Lattanzi A. Catal. Today 2017; 285: 39
• 7d Helene P. Lett. Org. Chem. 2018; 15: 171
• 7e Roma E, Tosi E, Miceli M, Gasperi T. Asian J. Org. Chem. 2018; 7: 2357
• 8 da Silva AR, dos Santos DA, Paixão MW, Corrêa AG. Molecules 2019; 24: 630
• 9 Cioc RC, Ruijter E, Orru RV. A. Green Chem. 2014; 16: 2958
• 10a Rivera DG, Paixão MW. Interplay between Organocatalysis and Multicomponent Reactions in Stereoselective Synthesis. In Stereochemistry and Global Connectivity: The Legacy of Ernest L. Eliel Volume 2, ACS Symposium Series 1258. American Chemical Society; Washington DC: 2017: 4-49
• 10b Lima CG. S, Moreira NM, Paixão MW, Corrêa AG. Curr. Opin. Green Sustain. Chem. 2019; 15: 7
• 11 Jiang J, Liu H, Lu C.-D, Xu Y.-J. Org. Lett. 2016; 18: 880
• 12 Minakata S, Ando T, Nishimura M, Ryu I, Komatsu M. Angew. Chem. Int. Ed. 1999; 37: 3392
• 13 Akiyama T, Suzuki T, Mori K. Org. Lett. 2009; 11: 2445
• 14a Gupta AK, Mukherjee M, Wulff WD. Org. Lett. 2011; 13: 5866
• 14b Gupta AK, Mukherjee M, Hu G, Wulff WD. J. Org. Chem. 2012; 77: 7932
• 15 Bew SP, Liddle J, Hughes DL, Pesce P, Thurston SM. Angew. Chem. Int. Ed. 2017; 56: 5322
• 16 Mukherjee M, Zhou Y, Dai Y, Gupta AL. K, Pulgam VR, Staples RJ, Wulff WD. Chem. Eur. J. 2017; 23: 2552
• 17 Zhou Y, Gupta AK, Mukherjee M, Zheng L, Wulff WD. J. Org. Chem. 2017; 82: 13121
• 18 Monteiro JL, Moreira NM, dos Santos DA, Paixão MW, Corrêa AG. Pure Appl. Chem. 2018; 90: 121
• 19a Deobald AM, Corrêa AG, Rivera DG, Paixão MW. Org. Biomol. Chem. 2012; 10: 7681
• 19b Deborah A, Maria A, Cornelio VE, Ávila RM. D, Cornea RC, Bernasconi GC. R, Paixão MW, Vieira PC, Corrêa AG. Bioorg. Med. Chem. 2017; 25: 4620
• 20a Vesely J, Ibrahem I, Zhao G.-L, Rios R, Córdova A. Angew. Chem. Int. Ed. 2007; 46: 778
• 20b Deiana L, Zhao G.-L, Lin S, Dziedzic P, Zhang Q, Leijonmarck H, Córdova A. Adv. Synth. Catal. 2010; 352: 3201
• 20c Deina L, Dziedzic P, Zhao G.-L, Vesely J, Ibrahem I, Rios R, Sun J, Córdova A. Chem. Eur. J. 2011; 17: 7904
• 21 Feu KA, Deobald AM, Narayanaperumal S, Corrêa AG, Paixão MW. Eur. J. Org. Chem. 2013; 5917
• 22 Arai H, Sugaya N, Sasaki N, Makino K, Lectard S, Hamada Y. Tetrahedron Lett. 2009; 50: 3329
• 23 Andraos J. Green Process Synth. 2019; 8: 324
• 24 Corrêa AG, Paixão MW, Deobald AM, Rivera DG. Reaction: Organocatalytic Asymmetric Tandem Epoxidation-Passerini Reaction . In Green Syntheses, Vol. 1, Green Syntheses Series. CRC Press; Boca Raton: 2014: 139-148
• 25 McElroy CR, Constantinou A, Jones LC, Summerton L, Clark JH. Green Chem. 2015; 17: 3111