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

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).