Deaminative ring contraction for the synthesis of polycyclic heteroaromatics: a concise total synthesis of toddaquinoline.

A concise strategy to prepare polycyclic heteroaromatics involving a deaminative contraction cascade is detailed. The efficient deaminative ring contraction involves the methylation of a biaryl-linked dihydroazepine to form a cyclic ammonium cation that undergoes a base-induced [1,2]-Stevens rearrangement/dehydroamination sequence. The presence of pseudosymmetry guides the retrosynthetic analysis of pyridyl-containing polycyclic heteroaromatics, enabling their construction by the reductive cyclization and deaminative contraction of tertiary amine precursors.

Scalable Synthesis and Cancer Cell Cytotoxicity of Rooperol and Analogues.

Plant polyphenols, such as the African potato ()-derived bis-catechol rooperol, can display promising anticancer activity yet suffer from rapid metabolism. Embarking upon a program to systematically examine potentially more metabolically stable replacements for the catechol rings in rooperol, we report here a general, scalable synthesis of rooperol and analogues that builds on our previous synthetic approach incorporating a key Pd-catalyzed decarboxylative coupling strategy. Using this approach, we have prepared and evaluated the cancer cell cytotoxicity of rooperol and a series of analogues.