Werner Stefan, Iyer Pravin S, Fodor Matthew D, Coleman Claire M, Twining Leslie A, Mitasev Branko, Brummond Kay M
University of Pittsburgh Center for Chemical Methodologies and Library Development, Pennsylvania 15260, USA.
J Comb Chem. 2006 May-Jun;8(3):368-80. doi: 10.1021/cc050160c.
The solution-phase synthesis of a discovery library of 178 tricyclic pyrrole-2-carboxamides was accomplished in nine steps and seven purifications starting with three benzoyl-protected amino acid methyl esters. Further diversity was introduced by two glyoxaldehydes and 41 primary amines. The combination of Pauson-Khand, Stetter, and microwave-assisted Paal-Knorr reactions was applied as a key sequence. The discovery library was designed with the help of QikProp 2.1, and physicochemical data are presented for all pyrroles. Library members were synthesized and purified in parallel and analyzed by LC/MS. Selected compounds were fully characterized.
以三种苯甲酰基保护的氨基酸甲酯为起始原料，通过九步反应和七次纯化完成了包含178个三环吡咯-2-甲酰胺的发现型文库的溶液相合成。通过两种乙二醛和41种伯胺引入了更多的多样性。将Pauson-Khand反应、Stetter反应和微波辅助的Paal-Knorr反应组合应用作为关键反应序列。借助QikProp 2.1设计了该发现型文库，并给出了所有吡咯的物理化学数据。文库成员并行合成、纯化并通过LC/MS进行分析。对选定的化合物进行了全面表征。
