Microwave Assisted ‘Click’ and ‘Cyclization’ of Peptoids on Solid Support – Synthesis and Characterization

Kaniraj Jeya Prathap, Chemistry, TECHNION, Haifa, Israel
Galia Maayan, Chemistry, TECHNION, Haifa, Israel

The design and synthesis of protein-like polymers has been a fundamental challenge for many decades. Peptoids, synthetic oligomers of modified glycines¹, are more diverse and differ from peptides in many aspects (i.e structure and function)². Cyclic peptoids are new class of peptidomimetic oligomers which have numerous unique properties and even greater advantages than linear peptoids.³ We present a highly efficient and more practical (azide-alkyne cycloaddition) click chemistry reaction and a cyclization protocol on solid support under microwave irradiation. We prepared four new peptoids bearing pyridine and picoline moieties and most importantly we succeeded in reducing our reaction time from 4 days to 40 minutes by using microwave irradiation on solid phase. Similarly, we have generated several cyclic peptoids with different sequences and microcycle sizes using a side to tail cyclization protocol, which is requires only a mild base as a reagent, and produces cyclic peptoids in high purity and yields. Both click and cyclic products were characterized by HPLC, LC-MS, CD and NMR spectroscopy.

References:

1. R.N. Zuckermann et.al  Proc. Nad. Acad. Sci. USA, 1992, 89, 9367-9371.

2. (a) Y-Uk. Kwon and T. Kodadek, J. Am. Chem.Soc., 2007, 129, 1508-1509; (b) S. M. Miller, R. J. Simon, S. Ng, R. N. Zuckermann, J. M. Kerr and W. H. Moos, Drug development research,1995, 35, 20-32.

3. S. B. Y. Shin, B. Yoo, L. J. Todaro and K. Kirshenbaum, J. Am. Chem.Soc., 2007, 129, 3218-3225