Isostere replacement is an established strategy in drug development. Recently, a surge in interest has been directed towards identifying isosteres for substituted aromatic rings. In particular, cubane and [1.1.1]-bicyclopentanes have shown promise as replacements for para-substituted aromatic rings. This is largely due to the similar positioning of substituents. As such, significant effort has been directed toward the synthesis and derivatization of cubane and [1.1.1]-bicyclopentanes. In contrast, isostere replacement for meta-substituted aromatic rings is significantly less well developed. In this seminar, a novel isostere for replacement of a meta-substituted aromatic ring is presented. We have identified that a cis-1,3-disubstituted [2]-ladderane (i.e., [2.2.0]-bicyclohexane) has a similar positioning of the substituents relative to a meta-substituted aromatic ring. A straightforward synthesis of a cis-1,3-disubstituted [2]-ladderane, representative derivatizations, and preliminary ADME properties will be discussed. Additional studies on the development of these structures will also be presented.

No strain, no gain: Advances in the synthesis and design of new classes of strained building blocks

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.