Syntheses and conformational studies of peptidomimetics of B-turns

Abstract

Syntheses of cyclic peptidomimeties of β-turns have been described. Three different cyclization methods were employed. The Sonogashira reaction was used to make a 14-membered ring in solution phase in modest yield. However, this reaction does not work well on solid supports. The S[]Ar and S[]2 reactions were used to synthesize macrocycles on solid phases. By using S[]Ar cyclization, libraries were made by parallel method on Geysen's pins. The products formed via different S[]2 cyclization conditions were characterized by COSY spectra. The base for cyclization was found to be important. To investigate the conformations of cyclic compounds systematically, the macrocycles with different ring sizes were used. The conformations were analyzed by NMR (COSY, ROESY, VT-NMR, D-H exchange experiments) and circular dichroism spectroscopy. One major conformer was found for each of these cyclic compounds. The cyclic peptidomimetics, from 13- to l6-membered rings, all resemble type I β-turns. This was especially true for the l4-membered rinse products which were designed as turn-extended-turn mimics.