Zhang Lei, Lushington Gerald H, Neuenswander Benjamin, Hershberger John C, Malinakova Helena C
Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045, USA.
J Comb Chem. 2008 Mar-Apr;10(2):285-302. doi: 10.1021/cc700151m. Epub 2008 Feb 1.
Parallel solution-phase synthesis of combinatorial libraries of hexahydro-1 H-isoindolones exploiting a novel "tactical combination" of Cu-catalyzed three-component coupling and Diels-Alder reactions was accomplished. Three distinct libraries consisting of 24 members (library I), 60 members (library II), and 32 members (library III) were constructed. Variation of three substituents on the isoindolone scaffold in library I was exclusively achieved by the choice of the building blocks. In the syntheses of libraries II and III, sublibraries of isoindolone scaffolds were prepared initially in a one-pot/two-step process and were further diversified via Pd-catalyzed Suzuki cross-coupling reaction with boronic acids at two different diversification points. The Lipinski profiles and calculated ADME properties of the compounds are also reported.
利用铜催化的三组分偶联反应和狄尔斯-阿尔德反应的新型“策略组合”，实现了六氢-1H-异吲哚酮组合库的平行溶液相合成。构建了三个不同的库，分别由24个成员（库I）、60个成员（库II）和32个成员（库III）组成。库I中异吲哚酮支架上三个取代基的变化完全通过构建模块的选择来实现。在库II和库III的合成中，异吲哚酮支架的子库最初通过一锅两步法制备，并在两个不同的多样化点通过与硼酸的钯催化铃木交叉偶联反应进一步多样化。还报道了这些化合物的Lipinski特性和计算得到的ADME性质。
