Stellane at the Forefront: Derivatization and Reactivity Studies of a Promising Saturated Bioisostere of ortho‐Substituted Benzenes

Abstract

This work highlights stellane's cage stability and derivatization opportunities. Using modern synthesis protocols, a di-verse range of building blocks were synthesized. Stellane's reactivity and chemical tolerance were rigorously evaluated across different reaction systems, demonstrating its promise as a bio-isosteric scaffold. It can be utilized in scaffold-based molecular design and offers topological precision superiority over existing ortho-isosteres, as well as mono-substituted benzene mimetics, holding the potential to become a robust platform for future medicinal chemistry studies.

Nature-Inspired Tetrahydropentalene Building Blocks: Scalable Synthesis for Medicinal Chemistry Needs

“…However, it is safe to consider readily available tetrahydropentalene-2,5-dione (2,5-THP-dione) as the foundational material for the synthesis of tetrahydropentalene-based building blocks. Besides the fact that 2,5-THP-dione is a commercial bulk chemical, in our previous studies on the synthesis of bis-nor adamantane (stellane) and nor-adamantane derivatives [6,7] we managed to adjust the literature protocol [8] for 2,5-THP-dione multikilo preparation. By leveraging the readily available and chemically versatile nature of 2,5-THPdione, we devised a scalable synthesis approach facilitating the production of these compounds at multigram scales with yields ranging from good to excellent.…”