Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as ortho-disubstituted benzene bioisosteres with improved biological activity.

Summary: Imagine building blocks for medicines. For a long time, chemists have relied on flat, six-sided rings (benzene) as a core component of many drugs. However, these flat shapes can sometimes limit how a drug interacts with the body or cause unwanted side effects.

Researchers have now developed a method using light and a specific acid catalyst to create a new 3D shape called a "bicyclo[2.1.1]hexane." Think of it as a 3D bridge structure that mimics the old flat ring but offers better properties. Crucially, this new method allows scientists to create "left-handed" and "right-handed" versions (enantiomers) of these molecules. When tested against tumor cells, these new 3D shapes not only worked as well as the original drugs but, in specific mirror-image forms, showed significantly improved ability to kill cancer cells. This discovery offers a powerful new tool for designing smarter, more effective medicines.