Exploring Reactivity of Acyclic Siloxydienes and Discovery, Synthesis and Study of HDAC Inhibitors

Developing novel reactions to activate distant molecular sites is crucial in organic synthesis and chemical exploration. Traditional methods often prioritize functionalizing nearby sites in a molecule. Yet, complex molecules often have unreactive remote sites that conventional techniques struggle to reach. An attractive strategy for remote activation and C–C bond formation involves the use of siloxydienes. New acyclic siloxydienes could serve to understand the reactivity of those systems at their gamma–position. Although important chemical transformations have been reported using cyclic and acyclic siloxydienes, limited data exists regarding the electronic factors influencing gamma–activation. In Medicinal chemistry, targeting HDACs has offered a powerful means to modulate gene expression and epigenetic changes, with potential applications in cancer treatment, neurological disorders, and more. Within the HDAC family, HDAC6 has emerged as a crucial participant in autophagy due to its association with several essential biological steps that collectively contribute to its impact on the autophagic process. The design, synthesis, and biological evaluation of new HDAC6 inhibitors are described. This newly developed library aims to make a meaningful contribution toward targeting melanoma and other diseases.