Blanco-Ania Daniel, Hermkens Pedro H H, Sliedregt Leo A J M, Scheeren Hans W, Rutjes Floris P J T
Institute for Molecules and Materials, Radboud University Nijmegen, Toernooiveld 1, Nijmegen, The Netherlands.
J Comb Chem. 2009 Jul-Aug;11(4):539-46. doi: 10.1021/cc800191w.
A structurally diverse library of potentially pharmacologically important compounds employing classical synthesis methods is described. These compounds are synthesized from beta-aryl pyrrolidines, providing products with the 2-arylethyl amine moiety, a structural feature often encountered in compounds active in the central nervous system. Tri- and tetracyclic scaffolds were obtained using the Pictet-Spengler reaction, resulting in hexahydropyrrolo[3,4-c]isoquinolines 1-3, an octahydropyrrolo[3',4':5,6]pyrido[3,4-b]indole 4, and a hexahydrofuro[2,3-d]pyrrolo[3,4-b]pyridine 5. These scaffolds were further derivatized in parallel fashion to make a 32-membered amide library with yields from 62 to 100% (90% average) and purities from 63 to 100% (93% average).
描述了一个采用经典合成方法构建的结构多样的潜在药理学重要化合物库。这些化合物由β-芳基吡咯烷合成，得到具有2-芳基乙胺部分的产物，这是在中枢神经系统活性化合物中经常遇到的结构特征。使用Pictet-Spengler反应获得了三环和四环骨架，得到了六氢吡咯并[3,4-c]异喹啉1-3、八氢吡咯并[3',4':5,6]吡啶并[3,4-b]吲哚4和六氢呋喃并[2,3-d]吡咯并[3,4-b]吡啶5。这些骨架以平行方式进一步衍生化，制成了一个32元酰胺库，产率为62%至100%（平均90%），纯度为63%至100%（平均93%）。
