Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, 20133 Milano, Italy.
J Org Chem. 2013 Mar 15;78(6):2600-10. doi: 10.1021/jo302737j. Epub 2013 Feb 21.
The synthesis of novel spirocyclic lactams, embodying D-tryptophan (Trp) amino acid as the central core and acting as peptidomimetics, is presented. It relies on the strategic combination of Seebach's self-reproduction of chirality chemistry and Pictet-Spengler condensation as key steps. Investigation of the conformational behavior by molecular modeling, X-ray crystallography, and NMR and IR spectroscopies suggests very stable and highly predictable type II' β-turn conformations for all compounds. Relying on this feature, we also pursued their application to two potential mimetics of the hormone somatostatin, a pharmaceutically relevant natural peptide, which contains a Trp-based type II' β-turn pharmacophore.
呈现了一种新型的螺环内酰胺的合成方法，其中包含 D-色氨酸（Trp）作为核心氨基酸，起到肽模拟物的作用。该方法依赖于 Seebach 的手性自复制化学和 Pictet-Spengler 缩合作为关键步骤的战略结合。通过分子建模、X 射线晶体学、NMR 和 IR 光谱学对构象行为的研究表明，所有化合物都具有非常稳定和高度可预测的 II'β-转角构象。基于这一特性，我们还探索了它们在两种潜在的生长抑素模拟物中的应用，生长抑素是一种具有药学相关性的天然肽，其中包含基于 Trp 的 II'β-转角药效团。
