Chemists discover 'impossible' molecules that break centuries -old binding rules
Chemists discover 'impossible' molecules that break centuries -old binding rules
For the first time chemist created, which was previously considered too unstable to exist and used to generate exotic connections 1 . Scientists say that these notorious molecules, known as anti-Bredt olefines (subscriptions), open a new way to the synthesis of challenging medicinal candidates.
The work is called "groundbreaking contribution", says Craig Williams, a chemist at the University of Queensland in Brisbane, Australia. The results were published in the magazine Science.
Organic molecules, the Carbon contain, typically take on specific forms that depend on the way the atoms are connected. For example, olefine, also known as alkenes-have hydrocarbons-often in reactions for Medicines Development -one or more double bonds between two carbon atoms, which leads to an arrangement of the atoms in one level.
The Bredt rule that has been known for 100 years, which in 1924 from Organic chemist Julius Bredt has been suggested that in small molecules that consist of two atoms, which are the case with some alkenes, double bonds between two carbon atoms at the rings connection point cannot occur. This is because the bonds would force the molecule into a complicated, tense 3D form that makes it highly reactive and unstable, says study coach Neil Garg, a chemist at the University of California, Los Angeles. "Nevertheless, 100 years later, people would still say that such structures are prohibited or too unstable to create them," he says.
Although the rule is anchored in chemical books, she has not prevented researchers from trying to break them. Earlier research indicated that it is possible to create subscriptions that have a double binding between carbon atoms at the connection point 2 . However, attempts to synthesize them in their complete form were unsuccessful because the reaction conditions were too hard, says Garg.
In the latest attempt, Garg and his colleagues dealt with a preliminary connection with a fluoride source in order to initiate a milder "elimination reaction" that removes atomic groups from molecules. This led to a molecule that had the characteristic subscription double binding. When the researchers added various fishing agents - chemicals that collect unstable molecules during the reaction - they were able to produce several complex connections that could be isolated. This indicates that the reactions of subscriptions can be used with different fishing agents to synthesize 3D molecules that are useful for the design of new medicines, says Garg.
In contrast to typical alkene,are subscriptions chiral compounds - molecules that do not perfectly coincide with their reflection. Garg and his colleagues synthesized and caught an enantio -rich subscription, which means that they produced more from a mirror -image couple than from the other. This result indicates that subscriptions could be used as unconventional building blocks for enantio -rich compounds that are widespread in pharmacy.
Chuang-Chuang Li, a chemist at Southern University of Science and Technology in Shenzhen, China, says that this approach could be used to explore innovative synthesis paths for other challenging molecules, such as the chemotherapy unit Paclitaxel (markets as a tax)-a complex, frequent molecule that is difficult in the laboratory is to be produced. "It's a valuable and reliable method," says Li.
Garg and his team examine further reactions with subscriptions and research how other molecules can be synthesized with apparently impossible structures. "We can think a little more creative," he says.
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McDermott, L. et al. Science 386, EADQ3519 (2024).