Synthesis and biological properties of spiroacetal-containing small molecules

Spiroacetals are attractive molecular frameworks for the development of high-quality compound collections for drug discovery projects. Firstly, these moieties play a key role in the biological outcome of the entire compound, whether directly interacting with the biological target or acting as a scaffold to address side chains into specific directions. Secondly, the distinct conformational flexibility of these frameworks assists the molecule in assuming the three-dimensional profile required for optimal binding to a biomacromolecule, resulting in a variety of different structural arrangements and subsequent biological outcomes. Modern advances in the efficient and selective synthesis of these skeletons are giving a great impulse in the use of acetal chemistry for the production of high-quality compound collections. In this chapter, we highlight the most versatile strategies to access spiroacetal molecular frameworks, and we report three examples of the synthesis of acetal-containing small molecule collections, together with the discussion of their biological outcomes.