Dallinger Doris, Kappe C Oliver
Christian Doppler Laboratory for Microwave Chemistry and Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
Nat Protoc. 2007;2(2):317-21. doi: 10.1038/nprot.2006.436.
We present here a protocol for the synthesis of the dihydropyrimidine (DHPM) derivative monastrol, which is known to be a specific mitotic kinesin Eg5 inhibitor. By applying controlled microwave heating under sealed-vessel conditions, the synthesis via the one-pot three-component Biginelli condensation can be performed in a shorter reaction time (30 min) compared with conventional heating methods that normally require several hours of reflux heating. For the purification of the crude target compound, two different methods are presented. The first protocol includes a simple precipitation/filtration step to provide monastrol in 76% isolated yield and high purity so that no recrystallization step is necessary. This can be ascribed to the microwave heating technology in which less side-product formation is typically one of the advantages. In an alternative purification step, column chromatography is performed, which provides the product in a slightly higher yield (86%). Monastrol synthesis can be conducted in approximately 2 h by employing the precipitation/filtration purification method.
我们在此展示一种合成二氢嘧啶（DHPM）衍生物莫那可林的方法，已知莫那可林是一种特异性的有丝分裂驱动蛋白Eg5抑制剂。通过在密封容器条件下进行可控微波加热，与通常需要数小时回流加热的传统加热方法相比，一锅三组分Biginelli缩合反应可在更短的反应时间（30分钟）内完成。对于粗目标化合物的纯化，介绍了两种不同的方法。第一种方法包括一个简单的沉淀/过滤步骤，可得到分离产率为76%且纯度高的莫那可林，因此无需重结晶步骤。这可归因于微波加热技术，其优点之一通常是副产物生成较少。在另一种纯化步骤中，进行柱色谱法，产物产率略高（86%）。采用沉淀/过滤纯化方法，约2小时即可完成莫那可林的合成。
