Divergent Cascade Construction of Skeletally Diverse Privileged Pyrazole-Derived Molecular Architectures

A powerful divergent cascade strategy has been explored for the easy construction of diverse enantioenriched pyrazole-derived scaffolds from readily available chiral fused pyrazole-tetrahydropyran acetals. These versatile intermediates can react in various ways to give Michael-aldol, reduction-lactonization, -hydroxylation-acetalization-oxidation, and Wittig-aldol and Wittig-oxa-Michael cascade reactions. Using only six simple building blocks, these processes gave five distinct molecular architectures. Furthermore, screening 10 compounds representing the 5 distinct scaffolds revealed potent anticancer lead compounds that deserve further development.