Himastatin is a bacterial natural product that has been studied over the past several decades for its antibiotic properties and intriguing structure. The compound is a dimer of peptide macrocycles linked through a bond between the aryl rings of two cyclotryptophan residues. While himastatin’s mechanism of action is not known, an early investigation demonstrated that its antibiotic activity was reduced in the presence of sodium salts of phospholipids and fatty acids, leading to speculation that himastatin may target the bacterial membrane. The most striking structural feature of himastatin is the central C5–C5' linkage between cyclotryptophan residues that is formed in the final biosynthetic step and is critical for the observed Gram-positive antibiotic activity.
What is New Strategy for Synthesizing the Natural Compound Himastatin？?
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- 3+ months ago by dybala
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- natural, past, over, structure, news, compound, product, strategy, antibiotics
Added 3+ months ago:
Chemists at MIT have developed a novel way to synthesize himastatin, a natural compound that has shown potential as an antibiotic. Using their new synthesis, the researchers were able not only to produce himastatin but also to generate variants of the molecule, some of which also showed antimicrobial activity. They also discovered that the compound appears to kill bacteria by disrupting their cell membranes.
This carbon-carbon bond is critical for the molecule’s antimicrobial activity. In previous efforts to synthesize himastatin, researchers have tried to make that bond first, using two simple subunits, and then added more complex chemical groups onto the monomers. The MIT team took a different approach, inspired by the way this reaction is performed in bacteria that produce himastatin. They began with a detailed examination of himastatin’s biogenesis from a linear peptide 4 that is cyclized and then subject to oxidative tailoring by three cytochrome p450 enzymes. The final step, catalyzed by HmtS, forges the central C5–C5' bond by oxidative dimerization of (+)-himastatin monomer. Based on recent theoretical studies of p450-catalyzed C–C bond formation, they envisioned that a biogenetically-inspired chemical method for the oxidative dimerization of cyclotryptophans could follow the same radical–radical coupling blueprint. Following this idea, the researchers were able to achieve concise total synthesis of himastatin by a newly developed final-stage dimerization strategy that was inspired by a detailed consideration of its biogenesis.
https://www.smolecule.com/news/synthesize-himastatin
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