In recent time, fragment-based drug discovery (FBDD) has quickly emerged as a widely recognized principle to discover lead compounds and chemical probes. In the Young Lab, we strive to achieve early-stage drug discovery through fragment library syntheses that emphasize the establishment of scaffold families, or groups of molecules that systematically and incrementally vary. More importantly, scaffold families invite the efficient exploration of chemical space through utilization of a central molecular template and generation of many substitution and stereochemistry patterns. The piperazine-based platform has been extensively used in many FDA approved drugs and many biologically important compounds, but its chemical diversity has been limited to nitrogen diversifications. We look to introduce substitutions on the <i>sp</i><sup>3</sup>-hybridized carbons and explore their powerful stereochemistry potential. Starting from various commercially available amino acids, a diverse array of monosubstituted piperazine scaffolds was constructed efficiently in a three-step process: the key step was an annulation reaction between a modified amino acid and bromoethylsulfonium salt to produce the desired piperazine compound.

Synthesis of enantiomerically pure orthogonally protected monosubstituted piperazines as intermediates for library production

2019 Fall National Meeting

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