Squaramides, Discovering a New Crucial Scaffold

Introduction

Interest in squaramides has grown drastically over the last few years. One of the reasons is that squaramides can be used in many different ways in important fields such as organic chemistry, medicine, and chemical biology.

First of all, the rigidity of their cyclobutadienedione rings, the restricted rotation around the C–N bonds,[1] and the possibility of having both acidic hydrogens[2] and basic functionalities in a single molecule make them effective bifunctional organocatalysts for asymmetric reactions.[3]

Furthermore, they act as ion detectors, forming hydrogen bonds with the corresponding anion or cation.[2b] [4] The interaction with anions through hydrogen bonding also brought them to the attention of studies regarding transmembrane anion transport.[5]

In addition, squaramides have shown antimalarial,[6] antibacterial,[7] and anticancer[8] activity.

• References

• 1 Rotger MC, Piña MN, Frontera A, Martorell G, Ballester P, Deyà PM, Costa A. J. Org. Chem. 2004; 69: 2302
• 2a Rostami A, Colin A, Li XY, Chudzinski MG, Lough AJ, Taylor MS. J. Org. Chem. 2010; 75: 3983
• 2b Amendola V, Bergamaschi G, Boiocchi M, Fabbrizzi L, Milani M. Chem.–Eur. J. 2010; 16: 4368

For interesting reviews, see:
• 3a Alemán J, Parra A, Jiang H, Jørgensen KA. Chem.–Eur. J. 2011; 17: 6890
• 3b Storer RI, Aciro C, Jones LH. Chem. Soc. Rev. 2011; 40: 2330
• 4a Tomàs S, Rotger MC, González JF, Deyà PM, Ballester P, Costa A. Tetrahedron Lett. 1995; 36: 2523
• 4b Jin C, Zhang M, Deng C, Guan Y, Gong J, Zhu D, Pan Y, Jiang J, Wang L. Tetrahedron Lett. 2013; 54: 796
• 4c Ramalingam V, Domaradzki ME, Jang S, Muthyala RS. Org. Lett. 2008; 10: 3315
• 5 Busschaert N, Kirby IL, Young S, Coles SJ, Horton PN, Light ME, Gale PA. Angew. Chem. Int. Ed. 2012; 51: 4426
• 6 Glória PM.C, Gut J, Gonçalves LM, Rosenthal PJ, Moreira R, Santos MM. M. Bioorg. Med. Chem. 2011; 19: 7635
• 7 Buurman ET, Foulk MA, Gao N, Laganas VA, McKinney DC, Moustakas DT, Rose JA, Shapiro AB, Fleming PR. J. Bacteriol. 2012; 194: 5504
• 8 Zhang Q, Xia Z, Mitten MJ, Lasko LM, Klinghofer V, Bouska J, Johnson EF, Penning TD, Luo Y, Giranda VL, Shoemaker AR, Steward KD, Djuric SW, Vasudevan A. Bioorg. Med. Chem. Lett. 2012; 22: 7615
• 9a Cheon CH, Yamamoto H. Tetrahedron 2010; 66: 4257
• 9b Ramalingam V, Bhagirath N, Muthyala RS. J. Org. Chem. 2007; 72: 3976
• 10 Malerich JP, Hagihara K, Rawal VH. J. Am. Chem. Soc. 2008; 130: 14416
• 11 Kardos G, Soós T. Eur. J. Org. Chem. 2013; 4490
• 12 Sanna E, Martínez L, Rotger C, Blasco S, González J, García-España E, Costa A. Org. Lett. 2010; 12: 3840
• 13 World Malaria Report 2012 of the World Health Organization: http://www.who.int/malaria/publications/world_malaria_report_2012/en/ (accessed on 26^th November 2013).
• 14 Sejwal P, Han Y, Shah A, Luk Y.-Y. Org. Lett. 2007; 9: 4897