Chorell Erik, Das Pralay, Almqvist Fredrik
Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden.
J Org Chem. 2007 Jun 22;72(13):4917-24. doi: 10.1021/jo0704053. Epub 2007 Jun 1.
Thiazolo ring-fused 2-pyridones have proven to be highly interesting scaffolds for the development of biologically active compounds. Many methods are today available to introduce a variety of substituents in the 2-pyridone part of the heterocycle. Herein we disclose how a diverse set of substituents can be introduced in the thiazolo ring, with possibilities to vary also the spatial arrangement of the substituents. A key intermediate is the oxidized framework 9 for which an effective synthesis is described. The thiazolo part of this system can be substituted either via conjugate additions, resulting in trans selectivity, or via microwave-assisted Heck couplings that result in unsaturated aryl-substituted analogues. The scaffold can also be lithiated followed by the addition of various electrophiles, which increases the diversification potential substantially, as exemplified with the introduction of halogens, alkyl, acyl, and amide substituents.
噻唑并稠合的2-吡啶酮已被证明是开发生物活性化合物的极具吸引力的骨架。如今有许多方法可用于在杂环的2-吡啶酮部分引入各种取代基。在此我们揭示了如何在噻唑环中引入多样的取代基，同时也有可能改变取代基的空间排列。一个关键中间体是氧化骨架9，文中描述了其有效的合成方法。该体系的噻唑部分可以通过共轭加成进行取代，得到反式选择性，或者通过微波辅助的Heck偶联反应得到不饱和芳基取代的类似物。该骨架也可以进行锂化，随后添加各种亲电试剂，这大大增加了多样化的潜力，如引入卤素、烷基、酰基和酰胺取代基的示例所示。
