LongLarf

Abstract

In this work, we reported a method for construction of difluorocyclopropanes through visible light-promoted [1+2] cycloaddition reaction of aryl diazo esters with gem-difluoroalkenes. The reaction proceeds under mild conditions, encompasses a wide range of substrates (36 examples), exhibits good tolerance to various substituents, and demonstrates a diastereoselectivity of >20:1. Additionally, antifungal activity evaluation revealed that these derivatives exhibited certain activity, the EC₅₀ values for the products towards Botrytis cinerea and Rhizoctonia solani were measured to be 1.51 and 1.36 μM, respectively, which are significantly lower than those of commercial fungicides Hymexazol and Azoxystrobin. This work not only provides an efficient method for the synthesis of difluorocyclopropanyl derivatives, but reveals their potential applications in fungicide creation.

Binding of precursor molecules to the side of a fibrous assembly of self-replicating macrocycles can improve the fidelity of replication and yield a novel error-correction mechanism, provided that the fibers bind selectively to precursors that match the building-block composition of the replicator.

Abstract

Copying information is vital for life‘s propagation. Current life forms maintain a low error rate in replication, using complex machinery to prevent and correct errors. However, primitive life had to deal with higher error rates, limiting its ability to evolve. Discovering mechanisms to reduce errors would alleviate this constraint. Here, we introduce a new mechanism that decreases error rates and corrects errors in synthetic self-replicating systems driven by self-assembly. Previous work showed that macrocycle replication occurs through the accumulation of precursor material on the sides of the fibrous replicator assemblies. Stochastic simulations now reveal that selective precursor binding to the fiber surface enhances replication fidelity and error correction. Centrifugation experiments show that replicator fibers can exhibit the necessary selectivity in precursor binding. Our results suggest that synthetic replicator systems are more evolvable than previously thought, encouraging further evolution-focused experiments.

Nature Chemical Biology, Published online: 26 February 2024; doi:10.1038/s41589-024-01563-y

A chemoproteomic method was developed that enables the global discovery of metal-binding proteins (MBPs) in proteomes, where the thermal stability of MBPs is perturbed by metal chelators. This tool, called METAL-TPP, is used to discover MBP candidates in the human proteome and provides a valuable method for functional annotation of MBPs in cell biology.

A cyclic deracemization process that utilizes alternately a biocatalytic enantioselective reduction employing (S)-selective methionine sulfoxide reductase from Pseudomonas alcaliphila (paMsr) supplemented with DTT as external reducing equivalent, and a stereo-unselective photocatalytic oxidation reaction using the readily accessible Eosin Y as photocatalyst to achieve chiral sulfoxides is presented. Evaluation of the substrate scope demonstrates a general applicability of this modular system.

Abstract

The synergistic combination of biocatalysis and photocatalysis is emerging as powerful tool for the development of sustainable and atom-efficient synthetic concepts facilitating an enormous portfolio of possible reactions which even goes beyond the capabilities found in nature. Here, a cyclic deracemization process is presented tailored for the synthesis of optically pure sulfoxides which are versatile structural motifs in asymmetric synthesis as well as in bioactive compounds. Enantioselective enzyme-catalyzed reduction of rac-sulfoxides was combined with a stereo-unselective photocatalytic oxidation of the corresponding sulfide intermediate. The utilization of the readily accessible and rather inexpensive photocatalyst Eosin Y increases the usability of this synthetic method. To overcome the incompatibility between the photocatalyst Eosin Y and the biocatalytic step, the cyclic deracemization process was performed in a step-wise fashion via alternated reduction in the darkness and oxidation under illumination. This modular system allowed precise adjustments of reaction parameters yielding the desired sulfoxide targets with up to >99 % ee. Evaluation of the substrate scope including a range of structurally diverse molecules demonstrated its broad applicability.

Enzyme engineering of O₂-dependent enzymes, such as oxidases and oxygenases, is crucial to increase their relevance in the chemical industry. Recently published studies will focus on optimising various aspects of O₂-dependent enzymes like activity, selectivity, specificity, substrate spectrum or stability by applying different enzyme engineering studies.

Abstract

Oxidation reactions catalysed by O₂-dependent enzymes are gaining increasing interest in the chemical industry due to their potential to provide a more selective and sustainable alternative to conventional chemical oxidation methods. O₂-dependent enzymes, like oxidases and oxygenases, catalyse a versatile range of oxidative reactions using only molecular oxygen as an oxidant. However, their practical application on a larger scale has been limited up to this point, primarily due to factors like their low catalytic rates combined with a narrow substrate spectrum and low stability. Nonetheless, enzyme engineering studies have significantly addressed these challenges in recent years and moved O₂-dependent enzymes closer towards industrial utilisation. This review aims to concisely overview the most recent engineering approaches to O₂-dependent enzymes. We will highlight recent studies that have targeted various aspects of O₂-dependent enzymes, including activity, selectivity, stability, and substrate spectrum, focusing on engineering studies where the engineered enzymes catalysed synthetically valuable reactions.

Nature Catalysis, Published online: 20 February 2024; doi:10.1038/s41929-024-01109-4

The direct cross-electrophile coupling of (hetero)aryl halides and pseudohalides is challenging. Now this reaction is facilitated by a visible light-induced palladium catalytic system that differentiates the reactants on the basis of the bond dissociation enthalpy affording unsymmetrical (hetero)biaryls.

An enzyme and a peptide catalyze—in an aqueous buffer—a two-step cascade reaction with high chemo- and stereoselectivity in one pot. The optimization of the modular peptide catalyst and the identification of common reaction conditions were key for bringing the two worlds of enzyme and peptide catalysis together.

Abstract

Enzymes and peptide catalysts consist of the same building blocks but require vastly different environments to operate best. Herein, we show that an enzyme and a peptide catalyst can work together in a single reaction vessel to catalyze a two-step cascade reaction with high chemo- and stereoselectivity. Abundant linear alcohols, nitroolefins, an alcohol oxidase, and a tripeptide catalyst provided chiral γ-nitroaldehydes in aqueous buffer. High yields (up to 92 %) and stereoselectivities (up to 98 % ee) were achieved for the cascade through the rational design of the peptide catalyst and the identification of common reaction conditions.

Unnatural amino acids, and their synthesis via the late-stage functionalization (LSF) of peptides, play a crucial role in areas such as drug design and discovery. Historically, the LSF of biomolecules has predominantly utilized traditional synthetic methodologies that exploit nucleophilic residues, such as cysteine, lysine or tyrosine. In this study, we present a photocatalytic hydroarylation process targeting the electrophilic residue dehydroalanine (Dha). This residue possesses an α,β-unsaturated moiety and can be combined with various arylthianthrenium salts, both in batch and flow reactors. Notably, the flow setup proved instrumental for efficient scale-up, paving the way for the synthesis of unnatural amino acids and peptides in substantial quantities. Our photocatalytic approach, being inherently mild, permits the diversification of peptides even when they contain sensitive functional groups. The readily available arylthianthrenium salts facilitate the seamless integration of Dha-infused peptides with a wide range of arenes, drug blueprints, and natural products, culminating in the creation of unconventional phenylalanine derivatives. The synergistic effect of the high functional group tolerance and the modular characteristic of the aryl electrophile enables efficient peptide conjugation and ligation in both batch and flow conditions.