DOS-like strategy for the spirocyclic MedChem relevant building blocks via Petasis / Grubbs reactions sequence

The efficient, preparative, and scalable DOS-like approach to 3D-shaped spirocyclic piperidines, including functionalized by carboxylic and additional amino functions, and azepanes based on Petasis/Grubbs reactions sequence in a multigram scale was elaborated. This strategy opens the door for novel 16 Bemis Murco scaffolds. The chemoinformatically generated amide-based compound libraries demonstrated significant expansion of the chemical space of tangible compounds (on the example of Enamine’s REAL database). This model study has shown broad perspectives on utilizing the DOS-like approach on the building block level in combination with well-developed methodologies for parallel synthesis for decoration and extension of ultra-large tangible chemical space to increase the speed and quality of drug discovery screening campaigns.