Govor Evgen V, Naumchyk Vasyl, Nestorak Ihor, Radchenko Dmytro S, Dudenko Dmytro, Moroz Yurii S, Kachkovsky Olexiy D, Grygorenko Oleksandr O
Enamine Ltd., Winston Churchill Street 78, Kyїv 02094, Ukraine.
Taras Shevchenko National University of Kyiv, Volodymyrska Street 60, Kyїv 01601, Ukraine.
Beilstein J Org Chem. 2024 Jul 16;20:1604-1613. doi: 10.3762/bjoc.20.143. eCollection 2024.
Parallel Groebke-Blackburn-Bienaymé reaction was evaluated as a source of multimillion chemically accessible chemical space. Two most popular classical protocols involving the use of Sc(OTf) and TsOH as the catalysts were tested on a broad substrate scope, and prevalence of the first method was clearly demonstrated. Furthermore, the scope and limitations of the procedure were established. A model 790-member library was obtained with 85% synthesis success rate. These results were used to generate a 271-Mln. readily accessible (REAL) heterocyclic chemical space mostly containing unique chemotypes, which was confirmed by comparative analysis with commercially available compound collections. Meanwhile, this chemical space contained 432 compounds that already showed biological activity according to the ChEMBL database.
平行的格罗布克-布莱克本-比内梅反应被评估为一个拥有数百万种化学可及化学空间的来源。在广泛的底物范围内测试了两种最流行的使用Sc(OTf)和对甲苯磺酸作为催化剂的经典方案，并且清楚地证明了第一种方法的普遍性。此外，还确定了该方法的范围和局限性。获得了一个由790个成员组成的模型库，合成成功率为85%。这些结果被用于生成一个包含2.71亿个易于获取的（真实的）杂环化学空间，其中大部分包含独特的化学类型，这通过与市售化合物集合的比较分析得到了证实。同时，根据ChEMBL数据库，这个化学空间包含432种已经显示出生物活性的化合物。
