This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Researchers from the Department of Chemistry at The University of Hong Kong (HKU), led by Professor Jian He and collaborators, have developed a new light-driven method for constructing three-dimensional molecular building blocks that could give medicinal chemists greater flexibility in designing new drug candidates. The approach broadens the range of starting materials that can be used while suppressing unwanted polymerization, overcoming key limitations of existing synthetic methods.
The findings have been published in Nature Chemistry. Benzene rings are among the most common structural building blocks in medicine. They are chemically stable and provide a useful framework for positioning other functional groups within a drug molecule.
However, their flat and relatively lipophilic nature can sometimes contribute to undesirable properties, such as poor water solubility or less favorable interactions with biological targets. Medicinal chemists are therefore increasingly exploring three-dimensional alternatives that can replace benzene rings while performing a similar structural role in drug molecules. One promising class is bicyclo[2.1.1]hexanes, or BCHs.
Their compact, three-dimensional shape offers researchers another way to fine-tune the shape and properties of drug molecules, potentially improving characteristics such as solubility, selectivity and metabolic stability. One important route to BCHs involves combining bicyclo[1.1.0]butanes, or BCBs, with alkenes. BCBs are highly strained small-ring molecules that serve as useful starting materials for building more complex three-dimensional structures.
However, synthesizing structurally diverse BCHs has remained difficult. Existing methods may work only with a limited range of starting materials and can also trigger unwanted polymerization or suffer from catalyst instability. Professor He's team and collaborators have now developed a new class of copper(I) photosensitizers that use visible light to drive this reaction.
After absorbing light, the copper complex transfers energy to one of the starting materials, enabling BCH structures to form in a more controlled manner. The new strategy expands the range of starting materials that can be used and allows chemists to control where different chemical groups are positioned on the BCH scaffold. The team also demonstrated gram-scale synthesis and further modification of the resulting BCHs with a variety of functional groups, highlighting the method's potential usefulness in medicinal chemistry and drug development.
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