Protocol abstract
Nature Protocols 2, - 317 - 321 (2007)
Published online: 1 March 2007 | doi:10.1038/nprot.2006.436
Subject Category: Synthetic chemistry
Rapid preparation of the mitotic kinesin Eg5 inhibitor monastrol using controlled microwave-assisted synthesis
Doris Dallinger1 & C Oliver Kappe1
Abstract
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 
2 h by employing the precipitation/filtration purification method.
- Christian Doppler Laboratory for Microwave Chemistry (CDLMC) and Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
Correspondence to: C Oliver Kappe1 e-mail: oliver.kappe@uni-graz.at; http://www.maos.net
nature-products
A-Z product listing
- 3-Hydroxybenzaldehyde(Sigma-Aldrich)
- Acetone(Acros)
- Acetonitrile(Fisher Scientific)
- Aluminum crimp(Biotage)
- Chloroform (CHCl3 (VWR)
- Ethyl acetoacetate(Acros)