🗣️ What was it like to work with a future Nobel laureate? Ivo Starý from our institute spoke about his experience in a Czech Television special – earlier in his career, he worked with Kensō Soai, one of the two chemists awarded today.

Applications for the 2027 MIT-Czech Republic IOCB Foundation Seed Fund are open! Organized by @mit-cis.bsky.social and funded by IOCB Foundation, the program supports early-stage collaborations between Czech researchers and their MIT colleagues with up to USD 25,000 per project. More info ⤵️

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.

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.

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.

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.

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.

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.

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.

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.