Monastrol Synthesis Using Subcritical EtOH: Response Surface Method for Optimization

Monastrol is an Eg5 inhibitor that induces mitotic arrest and apoptosis. The efficiency of the Biginelli reaction for Monastrol synthesis can be enhanced by utilizing a subcritical EtOH. The response surface method was employed to optimize the synthesis yield of subcritical EtOH by varying the parameters of temperature, pressure, and reaction time. The synthesis yield of Monastrol using the optimum subcritical EtOH method was compared with the flux method, both utilizing three different catalysts: sodium hydrogen sulfate, hydrochloric acid, and ytterbium trifluoromethanesulfonate. The synthesis yield of Monastrol using the optimum subcritical EtOH method was found to be significantly higher compared to the flux method. Furthermore, the catalysts sodium hydrogen sulfate and ytterbium trifluoromethanesulfonate exhibited improved synthesis yield in comparison to the acid-catalyzed reactions. Additionally, the findings obtained from thin-layer chromatography confirmed the results obtained from LC-MS analysis. This innovative approach can be extended to other heteroaromatic aldehydes