All-L-Leu-Pro-Leu-Pro: A challenging cyclization

In this paper, we report the difficult synthesis of cyclo(Leu-Pro-Leu-Pro). While the cyclization of Leu-Pro-Leu-D-Pro did not cause problems, the all -L-peptide afforded cyclodimer rather than cyclotetrapeptide (cyclomonomer) . A first attempt using our reversible backbone substitution methodology fa iled. However, we were successful in obtaining the desired cyclo(Leu-Pro-Le u-Pro) by decreasing the concentration. The ratio of cyclomonomer to cyclod imer was raised to 1:1.1 using BOP and 1:0.6 using HATU under our high dilu tion condition. The structures of the cyclopeptides were confidently assign ed by electrospray ionization mass spectrometry and NMR. Copyright (C) 2000 European Peptide Society and John Wiley & Sons. Ltd.