Design and synthesis of Fsp3-rich, bis-spirocyclic-based compound libraries for biological screening.

The exploration of innovative chemical space is a critical step in the early phases of drug discovery. Bis-spirocyclic frameworks occur in natural products and other biologically-relevant metabolites and show attractive features such as molecular compactness, structural complexity and three-dimensional character. A concise approach to the synthesis of bis-spirocyclic-based compound libraries starting from readily available commercial reagents and robust chemical transformations has been developed. A number of novel bis-spirocyclic scaffold examples, as implemented in the European Lead Factory project, is presented.