Tropanes in natural products, syntheses, and drugs: some insights from the new millennium.

The term "tropane" refers to the 8-azabicyclo[3.2.1]octane core, first discovered in the tropane alkaloids produced by certain families of plants. These alkaloids, which are likely plant defense compounds, have well-precedented bioactivities such as muscarinic receptor antagonism and dopamine transporter (DAT) inhibition. The long-standing usefulness of alkaloids such as atropine, scopolamine, and cocaine has encouraged the incorporation of the tropane moiety into multiple other approved drugs, likely cementing its place as a privileged scaffold. Because of their diverse utility and efficacy, tropane-containing compounds are still an area of very active investigation. A quarter of the way through the new century, novel tropane alkaloids are still being discovered, imaginative and applicable ways to make these compounds are being revealed, and tropane-containing molecules have proven to be promising avenues for treatment of central nervous system (CNS) disorders, cancer, diabetes, viral infections, and many other conditions, as well as effective diagnostic agents and tool compounds. This review summarizes recent (2015-2025) developments concerning tropane-containing molecules. New natural products, synthetic strategies to construct and functionalize the tropane core, drug hits, leads, and clinical candidates, and other relevant molecules containing tropane moieties are described. An overview of where the "tropane field" is headed, with focus on finding, analyzing, and obtaining high-value alkaloids and analogs (and re-imagining drug synthesis and discovery in an increasingly technological and environmentally conscious age) is also provided.