American Chemical Society
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Design, Synthesis, and Conformational Analysis of Trispyrimidonamides as α‑Helix Mimetics

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journal contribution
posted on 2014-02-21, 00:00 authored by Lukas Spanier, Emanuele Ciglia, Finn K. Hansen, Krystina Kuna, Walter Frank, Holger Gohlke, Thomas Kurz
The straightforward synthesis of trispyrimidonamides as a new class of α-helix mimetics is reported. Because of the versatility of our synthetic protocol, a variety of side chains including aliphatic, basic, aromatic, and heteroaromatic residues were included. A comprehensive conformational analysis revealed that in polar solvents a trimeric compound adopts conformations that can lead to i, i + 4, i + 8, or i, i + 8 patterns of side chain orientation. This suggests that trispyrimidon­amides could be promising α-helix mimetics to target hot spots that are distributed over a wider angular range of an α-helix interface than in the classical i, i + 4, i + 7 case.