Werner S, Turner D M, Chambers P G, Brummond K M
Center for Chemical Methodologies & Library Development (UPCMLD), University of Pittsburgh, Pittsburgh PA, 15260, USA.
Tetrahedron. 2008 Jul 14;64(29):6997-7007. doi: 10.1016/j.tet.2008.02.033.
Amino acid-derived cross-conjugated trienes were used as a starting point for the synthesis of a discovery library of over 200 polycyclic 5-iminooxazolidin-2-ones, hydantoins, and acylureas. The main feature of this library synthesis is a triple branching strategy which provides efficient access to five skeletally diverse scaffolds. In addition, four sets of building blocks were applied in both a front end and a back end diversification strategy. Multiple fused rings were obtained by cyclization of diamides with phosgene and stereoselective Diels-Alder reactions with maleimides. The 5-iminooxazolidin-2-one scaffold was rearranged into the isomeric hydantoin scaffold through a sequence of ring opening and ring closing reactions.
以氨基酸衍生的交叉共轭三烯为起点，合成了一个包含200多种多环5-亚氨基恶唑烷-2-酮、乙内酰脲和酰脲的发现库。该库合成的主要特点是一种三重分支策略，该策略可有效获得五种骨架不同的支架。此外，在前端和后端多样化策略中都应用了四组构建块。通过二酰胺与光气的环化反应以及与马来酰亚胺的立体选择性狄尔斯-阿尔德反应获得多个稠环。5-亚氨基恶唑烷-2-酮支架通过一系列开环和闭环反应重排为异构体乙内酰脲支架。
