Search

Several solid- and solution-phase strategies were evaluated for the preparation of libraries of polysubstituted piperidines of type 7using the tandem aza42cycloaddition/allylboration multicomponent reaction between 1-aza-4-boronobutadienes, maleimides, and aldehydes. A novel four-component variant of this chemistry was developed in solution phase, and it circumvents the need for pre-forming the azabutadiene component. A parallel synthesis coupled with compound purification by HPLC with mass-based fraction collection allowed the preparation of a library of 944 polysubstituted piperidines in a high degree of purity suitable for biological screening. A representative subset of 244 compounds was screened against a panel of phosphatase enzymes, and despite the modest levels of activity obtained, this study demonstrated that piperidines of type 7display the right physical properties (e.g., solubility) to be assayed effectively in high-throughput enzymatic tests. [ABSTRACT FROM AUTHOR]