□ The team, led by Professor Seo Sang-won from DGIST's Department of Chemical Physics, in collaboration with the Molecular Activation Catalysis Research Team of IBS (headed by Professor Seok-bok Jang from KAIST), successfully developed a catalytic system to efficiently obtain beta-lactam structures, key raw materials of bioactive substances. This new catalyst uses abundant hydrocarbons as raw materials and can synthesize antibiotics such as penicillin. It is expected to be applicable in various fields.
□ In 1928, Alexander Fleming, a British biologist, discovered penicillin, the first antibiotic, from blue mold. Later, in 1945, British chemist Dorothy Hodgkin revealed that the key structure of penicillin consists of a ring compound called beta-lactam. Beta-lactam is a four-membered lactam with a ring structure made up of three carbon atoms and one nitrogen atom. It forms the backbone of key antibiotics, including carbapenems and cefalexin, in addition to penicillin.
□ Thanks to the elucidation of penicillin's structure, humans have been able to chemically synthesize beta-lactam-based antibiotics. However, even after approximately 80 years, challenges remain in the synthesis of beta-lactam. Beta-lactam can possess chirality[1], which means that despite having the same number and type of atoms, there exist two mirror-image isomers with completely different properties.
□ Most commercially available beta-lactam drugs are manufactured selectively for the useful isomer by attaching them to chiral auxiliaries during the synthesis process. This complicates the synthesis, increases production costs, and generates waste due to the additional chemicals needed to remove the auxiliaries.
□ The research team succeeded in selectively synthesizing difficult-to-produce beta-lactam using an affordable and abundant nickel catalyst. In commercial processes, the beta-lactam raw materials needed for antibiotic synthesis were synthesized in approximately eight steps. However, the team's proposed catalysis eliminates the need for auxiliary attachment and removal, reducing the process to approximately three steps.
□ This study shows potential for creating high-value-added products by synthesizing materials with an approximately 700 times higher market value from hydrocarbon compounds. The team also succeeded in accurately introducing the beta-lactam backbone into complex chemical structures such as natural compounds. Thus, new candidate drugs can be synthesized more simply than using existing pharmaceutical synthesis strategies.
□ Professor Seo Sang-won of the Department of Chemical Physics said, "We synthesized high-added-value chiral beta-lactam with high accuracy from naturally abundant hydrocarbon raw materials using inexpensive first-row transition metal nickel catalysts. This can significantly shorten the synthesis process for pharmaceutical substances such as carbapenem and sitagliptin. This makes it an important discovery with a high likelihood of wide-ranging applications in accelerating drug development within the industry.”
□ The research findings were published online in Nature Catalysis (Impact Factor 37.8), an esteemed journal in the chemical field, on August 25, Korean time.
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[1] Chirality: A characteristic of molecules that have the same chemical formula but different physical, chemical, and optical properties. Chirality or mirror-image isomerism is akin to comparing your left and right hands in a mirror; they look the same but can never be superimposed, regardless of how much you rotate them. It is crucial to consider chirality in drug synthesis because while one type of isomer may be useful, the other could be toxic.
