UCLA chemists overturn 100-year chemistry rule, opening new doors for drug development
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In a groundbreaking discovery, researchers at UCLA have challenged Bredt’s rule, a core principle in organic chemistry, paving the way for potential advancements in drug development.
Led by Professor Neil Garg, the UCLA team successfully synthesized and stabilized anti-Bredt olefins (ABOs)—a type of molecular structure long believed to be too unstable to exist - thereby overturning the century-old guideline that has restricted molecular design for decades.
First proposed by chemist Julius Bredt in 1924, Bredt’s rule has asserted that double bonds cannot reside at the bridgehead position in certain molecules due to stability concerns. This rule has served as a structural limitation in organic chemistry, particularly impacting the design of synthetic compounds in pharmaceuticals by excluding certain 3D molecular configurations that could enhance drug function.
In a recent Science publication, Professor Garg’s team outlined a novel method to create ABOs.
By reacting silyl (pseudo)halides with fluoride, the researchers induced an elimination reaction that led to the formation of ABOs. To stabilize these reactive compounds, the team added a trapping agent, allowing them to isolate useful reaction products for further experimentation. This controlled approach marks a significant leap in organic chemistry, as it enables chemists to explore new molecular structures previously thought unachievable.
The pharmaceutical industry is increasingly interested in designing 3D molecular structures, like those now accessible with ABOs, to create more effective drugs.
Garg noted that this discovery could drive unprecedented innovation in drug design by expanding the types of compounds available to researchers. Professor Ken Houk, a computational chemistry expert and study co-author, also highlighted the practical applications of these compounds, underscoring the potential for ABOs to unlock new avenues in synthetic chemistry.
The UCLA team’s findings invite chemists to view molecular rules more as adaptable guidelines than absolute constraints, suggesting a future where innovation in chemistry and drug discovery is only limited by creativity and curiosity.
