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Abbasi Kejani, A.; Dey, P.; Stillman, N. H.; Andrade, D. M.; Šimek, M.; Dračínský, M.; Bím, D.; Paioti, P. H. S. Synthesis of Large- and Medium-Sized Heterobiaryl Atropisomeric Rings and Atropopeptides by Catalytic Intramolecular SNAr. Angew. Chem. Int. Ed. 2026, e8290035. doi.org/10.1002/anie...

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Most of the synthesis resulted from collaborative effort within the Paioti group, involving PhD students Alireza Abbasi Kejani and Paritosh Dey, and Marie Skłodowska-Curie postdoctoral fellow Nicholas Stillman and undergraduate student Daniel de Andrade.

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The work impacts synthesis and catalysis broadly. It brings attention to a new way of synthesizing cyclic heterobiaryl molecular architectures available for drug discovery, and to a concept in catalysis which is to inspire other challenging and useful substitution and addition reactions.

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Preparation of these cyclic peptides will enable bioactivity screenings in search of compounds with anticancer and antibacterial properties. Such studies will also shed light on the impact of atropisomerism on the molecules’ pharmacological properties.

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This enabled the synthesis of structurally and stereochemically diverse atropopeptides inspired by naturally occurring ribosomally synthesized and post-translationally modified peptides (RiPPs), known as RiPPs.

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Many of the resulting compounds have three-dimensional shapes and stereochemistry that are of particular interest in medicinal chemistry. The researchers applied the reaction to direct cyclization of tryptophan-containing peptides.

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Mechanistic aspects have been studied experimentally and computationally with Daniel Bím from @vschtpraha.bsky.social. The method makes it possible to construct strained medium-sized rings and macrocycles directly from linear precursors with a N-heterocycle head and an aryl fluoride tail.

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The new method avoids this limitation through use of a fluoride catalyst in combination with an organosilane, described by the authors as a base-embedding electrophile, allowing the active base to be regenerated through a different catalyst turnover mechanism.

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The key innovation lies in the way the reaction generates and regenerates a strong base. In many base-catalyzed substitution reactions, catalyst turnover is inefficient because the leaving group is not sufficiently basic.

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The approach enables the direct formation of sterically hindered carbon–nitrogen bonds through an intramolecular nucleophilic aromatic substitution (SNAr) reaction and provides access to highly strained atropisomeric macrocycles, medium-sized rings and atropopeptides.

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⚗️ Researchers led by Paulo Paioti from IOCB Prague have developed a new catalytic macrocyclization strategy for synthesis of cyclic molecules that are difficult to obtain by conventional methods... 🧵 #organicsynthesis #research #IOCB #IOCBPrague

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Read the paper: Sahatsapan, N. et al.; Rejman, D. Polycaprolactone and poly(vinyl alcohol) electrospun single-layer nanofiber materials loaded with novel antibacterial LEGO-LPPO for advanced wound dressing. Biomaterials Advances 2026, November, 215039. doi.org/10.1016/j.bi...

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It led to near-complete prevention of severe infection and strongly reduced the bacterial burden in the wound. The study establishes LEGO-LPPO-loaded nanofibrous dressings as a promising platform for topical infection control.

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The compound was well tolerated by keratinocytes and did not impair keratinocyte migration, while fibroblasts were somewhat more sensitive at higher concentrations or after longer exposure. In a prophylactic mouse model of S. aureus infection, the fast-release PVA-based formulation performed best.

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PCL-based materials released LEGO-LPPO 5 more slowly, but release was accelerated when the polymer was degraded by lipase. All LEGO-LPPO-containing materials showed antibacterial activity, with the strongest effects observed for PVA- and PCL-based formulations containing higher LPPO loadings.

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The team incorporated LEGO-LPPO 5 into two types of nanofiber materials: poly(vinyl alcohol), or PVA, and polycaprolactone, or PCL. The two carriers behaved differently. PVA-based materials released the antibacterial agent rapidly, while thermal stabilization slowed this burst release.

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A key challenge is to develop wound dressings that release antibacterials where they are needed. #IOCBPrague, Pavol Jozef Šafárik, @tuliberec.bsky.social, Palacký University, @vschtpraha.bsky.social, @charlesuni.cuni.cz developed wound dressings loaded with antibacterial agent LEGO-LPPO 5.

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