化学
转氨作用
亚胺
烯胺
哌啶
对映选择合成
组合化学
立体化学
生物转化
手性(物理)
全合成
有机化学
催化作用
酶
Nambu–Jona Lasinio模型
手征对称破缺
物理
量子力学
夸克
作者
Philipp Petermeier,Christoph Kohlfuerst,Ana Torvisco,Roland Fischer,Alejandro Mata,Doris Dallinger,C. Oliver Kappe,Joerg Schrittwieser,Wolfgang Kroutil
标识
DOI:10.1002/adsc.202300050
摘要
Substituted piperidine rings are a common motif in natural products and pharmaceutical drugs. The asymmetric synthesis of piperidines bearing multiple stereocentres remains a challenge, and current approaches often rely on lengthy reaction sequences and ‘chiral pool’ strategies. Herein, we report multi-enzymatic and chemo-enzymatic methods that allow the preparation of piperidines with three chirality centres in only two steps from achiral diketoester precursors. Stereocontrol is achieved by a highly enantioselective transamination leading to optically pure (ee >99%) enamine or imine intermediates, followed by diastereoselective reduction of these unsaturated N-heterocycles using either platinum(0)-catalysed flow hydrogenation or enzymatic imine reduction. In the latter case, coupling of the two biocatalytic reactions in a concurrent one-pot process is possible, thus reducing the synthetic sequence to a single biotransformation. In total, nine trisubstituted piperidines were prepared in high stereoisomeric purities (dr ≥98:2) and isolated yields of up to 73%. Lead-likeness analysis of five representative products using an open-source webtool suggests that these compounds possess considerable application potential as building blocks in drug discovery.
科研通智能强力驱动
Strongly Powered by AbleSci AI