BIreactive: Expanding the Scope of Reactivity Predictions to Propynamides

We present the first comprehensive study on the prediction of reactivity for propynamides. Covalent inhibitors like propynamides often show improved potency, selectivity, and unique pharmacologic properties compared to their non-covalent counterparts. In order to achieve this, it is essential to tune the reactivity of the warhead. This study shows how three different in silico methods can predict the in vitro properties of propynamides, a covalent warhead class integrated into approved drugs on the market. Whereas the electrophilicity index is only applicable to individual subclasses of substitutions, adduct formation and transition state energies have a good predictability for the in vitro reactivity with glutathione (GSH). In summary, the reported methods are well suited to estimate the reactivity of propynamides. With this knowledge, the fine tuning of the reactivity is possible which leads to a speed up of the design process of covalent drugs

A Highly Diastereoselective Recognition Process as the Basis for the Resolution of Palladatricyclo[4.1.0.0^2,4]heptanes

The synthesis of palladatricyclo­[4.1.0.0^2,4]­heptane diastereomers by positional selective transesterification with (1<i>R</i>,2<i>S</i>,5<i>R</i>)-(−)-menthol is used for the resolution of these chiral organometallic compounds. The separation process of the two diastereomers is simplified by an unprecedented aggregation phenomenon. In a molecular recognition process the highly diastereoselective formation of dimers of strongly differing stability allows an efficient separation by normal column chromatography. The stereoselective dimerization was proven by IR and mass spectroscopic studies as well as ¹H NMR techniques and X-ray crystal structure analysis

A Highly Diastereoselective Recognition Process as the Basis for the Resolution of Palladatricyclo[4.1.0.0^2,4]heptanes

The synthesis of palladatricyclo­[4.1.0.0^2,4]­heptane diastereomers by positional selective transesterification with (1<i>R</i>,2<i>S</i>,5<i>R</i>)-(−)-menthol is used for the resolution of these chiral organometallic compounds. The separation process of the two diastereomers is simplified by an unprecedented aggregation phenomenon. In a molecular recognition process the highly diastereoselective formation of dimers of strongly differing stability allows an efficient separation by normal column chromatography. The stereoselective dimerization was proven by IR and mass spectroscopic studies as well as ¹H NMR techniques and X-ray crystal structure analysis