Nickel Sabrina, Nickel Philipp, Hellmert Marco, Ernst Silvia, Jewell Robert, Pearce Christopher A, Jones Geraint, Hamza Daniel, Kaiser Markus
Chemical Biology, Zentrum für Medizinische Biotechnologie (ZMB), Fakultät für Biologie, Universtität Duisburg-Essen, Universitätsstr. 2, 45117 Essen, Germany.
Sygnature Discovery, BioCity, Pennyfoot Street, Nottingham NG1 1GF, United Kingdom.
Bioorg Med Chem. 2015 Jun 1;23(11):2636-45. doi: 10.1016/j.bmc.2015.04.003. Epub 2015 Apr 10.
Scaffolds of natural products represent promising starting points for the development of focused compound libraries. Here, we describe the development of a synthetic route to a compound library based on the hexahydropyrrolo indole (HPI) scaffold, the denoting structural motif of the HPI natural product family. To this end, a two-step approach consisting of a batch synthesis of an advanced functionalizable HPI intermediate followed by the establishment of reaction conditions that allow derivatization of this scaffold at three different positions is described. Subsequently, the optimized methods were applied to the synthesis of a 276-member library.
天然产物支架是开发聚焦化合物库的有前景的起点。在此，我们描述了一条基于六氢吡咯并吲哚（HPI）支架的化合物库合成路线的开发，HPI支架是HPI天然产物家族的标志性结构基序。为此，描述了一种两步法，包括先进的可官能化HPI中间体的分批合成，随后建立允许在该支架的三个不同位置进行衍生化的反应条件。随后，将优化后的方法应用于一个276成员库的合成。
