McLeod Michael C, Aubé Jeffrey
The University of Kansas Center of Excellence in Chemical Methodologies and Library Development (KU-CMLD), 2034 Becker Drive, Del Shankel Structural Biology Center, Lawrence, Kansas 66047, United States.
Tetrahedron. 2016 Jun 30;72(26):3766-3774. doi: 10.1016/j.tet.2016.03.016.
The preparation of sp-rich scaffolds to obtain more natural product-like libraries for incorporation into screening decks is challenging. Here, we describe the use of a Diels-Alder reaction between an enone and an azide-containing silyloxydiene to gain efficient access to complex tricyclic amine scaffolds. Derivatization of these scaffolds provided a library of 80 amines, amides, sulfonamides, quinolines and indolenines, all in >20 mg quantities and >90% purities. These library compounds displayed properties more similar to alkaloid natural products than to drugs and commercial drug-like libraries, as shown by a high proportion of sp carbon centers.
制备富含sp的支架以获得更多类似天然产物的文库用于纳入筛选平台具有挑战性。在此，我们描述了使用烯酮与含叠氮基的硅氧基二烯之间的狄尔斯-阿尔德反应，以有效地获得复杂的三环胺支架。这些支架的衍生化提供了一个包含80种胺、酰胺、磺酰胺、喹啉和吲哚啉的文库，所有化合物的量均大于20 mg，纯度大于90%。如高比例的sp碳中心所示，这些文库化合物显示出与生物碱天然产物更相似的性质，而不是与药物和商业类药物文库相似。
