A theoretical and experimental investigation of vicinal tricarbonyl systems and their hydrates

The conformational preferences of the vinyl vicinal tricarbonyl reagent (ETC) and related triketones have been examined in the context of ab initio molecular orbital theory in order to better understand the properties of these reactive polyelectrophiles. The preferred conformation of the ETC methyl ester has been calculated to have the glyoxal unit twisted almost perpendicular to the plane of the ester unit. These results support the recent conclusions of Schreiber and co-workers on the activity of FK-506 and related compounds for inhibition of the rotamase enzyme. The origin of the enhanced reactivity has been examined via an analysis of the charge density distributions of the triketones and the corresponding hydrates. Electrostatic stabilization appears to be the main driving force for the stability of the hydrates