DOS‐Like Strategy for the Spirocyclic MedChem Relevant Building Blocks via Petasis / Grubbs Reactions Sequence

Abstract Through this model study, we showed broad perspectives on utilizing the diversity‐oriented synthesis (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. This strategy led us to 16 novel Bemis‐Murco scaffolds based on spirocyclic functionalized piperidines. The efficient, preparative, and scalable DOS‐like approach to the above‐mentioned motif was achieved by Petasis/Grubbs reactions sequence on a multigram scale. 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).