Mu Boshuai, Mu Linjing, Schibli Roger, Ametamey Simon M, Milicevic Sephton Selena
Center of Radiopharmaceutical Sciences of ETH, PSI and USZ, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.
Department of Nuclear Medicine, University Hospital Zurich, Ramistrasse 101, 8003 Zurich, Switzerland.
Pharmaceuticals (Basel). 2018 Feb 20;11(1):24. doi: 10.3390/ph11010024.
The Sonogashira cross-coupling, a key step in the syntheses of the mGlu₅ antagonists MMPEP and MTEP, provided an improved three-step method for the preparation of MMPEP in 62% overall yield. Using Spartan molecular modeling kit an explanation for the failure to employ analogues method in the synthesis of MTEP was sought. The DFT calculations indicated that meaningful isolated yields were obtained when the HOMO energy of the aryl halide was lower than the HOMO energy of the respective alkyne.
Sonogashira交叉偶联反应是代谢型谷氨酸受体5（mGlu₅）拮抗剂MMPEP和MTEP合成中的关键步骤，它为制备MMPEP提供了一种改进的三步法，总收率为62%。使用Spartan分子建模工具包，试图为在MTEP合成中未能采用类似方法寻找原因。密度泛函理论（DFT）计算表明，当芳基卤化物的最高占据分子轨道（HOMO）能量低于相应炔烃的HOMO能量时，可获得有意义的分离产率。
