Synthesis of Macrocycles Containing 1,2,3-Triazole Motifs

Abstract

A new procedure for the preparation of macrocycles containing 1,2,3-triazole motifs is developed. The macrocyclic precursor is constructed by repetition of a series of steps which include cycloaddition of an azide with an alkyne, alkylation of a carboxylic acid with propargyl bromide and formation of an azide from an amino group. The order of the steps and the size of the connected fragments are determined by the desired ring size. Chromatographic purification techniques for the poorly soluble final products are also described.

Key words

macrocycles - 1,2,3-triazole - cycloaddition - azidobenzoate - propargyl ester

• References

• 1 Wessjohann LA, Ruijter E, Garcia-Rivera D, Brandt W. Mol. Diversity 2005; 9: 171
• 2 Tyndall JD. A, Fairlie DP. Curr. Med. Chem. 2001; 8: 893
• 3 Nishino N, Wagner RN, Lindsey JN. J. Org. Chem. 1996; 61: 7534
• 4 Hellier PC, Bradshaw JS, Young JJ, Zhang XX, Izatt RM. J. Org. Chem. 1996; 61: 7270
• 5 Rajakumar P, Murali V. Tetrahedron 2000; 56: 7995
• 6 Kim SH, Choi SH, Kim J, Lee SJ, Quang DT, Kim JS. Org. Lett. 2010; 12: 560
• 7 Pirali T, Tron GC, Zhu J. Org. Lett. 2006; 8: 4145
• 8 Chandrasekhar S, Rao CL, Nagesh C, Reddy CR, Sridhar B. Tetrahedron Lett. 2007; 48: 5869
• 9 Yanai H, Taguchi T. Tetrahedron Lett. 2005; 46: 8639
• 10 Ray A, Manoj K, Bhadbhade MM, Mukhopadhyay R, Bhattacharjya A. Tetrahedron Lett. 2006; 47: 2775
• 11 Shao C, Wang X, Xu J, Zhao J, Zhang Q, Hu Y. J. Org. Chem. 2010; 75: 7002
• 12 Chen H, Zuo S, Tang X, Zhao M, Lu Y, Chen L, Liu J, Liu Y, Liu D, Zhang S, Li T, Wang X. Eur. J. Med. Chem. 2011; 46: 4709
• 13 Majumdar KC, Ray K. Synthesis 2011; 3767
• 14 Hradilová L, Grepl M, Hlaváč J, Lyčka A, Hradil P. J. Heterocycl. Chem. 2012; in press
• 15 Garanti L, Molteni G, Zecchi G. Heterocycles 1994; 38: 291
• 16 More SS, Shanmughapriya D, Lingam Y, Patel NB. Synth. Commun. 2009; 39: 2058