LongLarf

Nature Communications, Published online: 04 May 2023; doi:10.1038/s41467-023-38228-8

Boronic acids are promising catalysts for the direct functionalization of alcohols without requiring precious metals. Here, the authors report an easily synthesized class of cyclic hemiboronic acid catalysts which are applicable in both nucleophilic and electrophilic modes of alcohol activation.

Synlett
DOI: 10.1055/a-2016-6577

An environmentally friendly stereoselective synthesis of 2,3-dihydrobenzofurans and 1,2,3-trisubstituted indanes in water has been achieved by using a permethylated β-cyclodextrin-tagged N-heterocyclic carbene–gold complex. The gold catalyst can be recycled at least five times.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

Separation not required: Mass spectrometry without prior chromatographic separation, carried out on a single-quadrupole HPLC-MS, can be used for the qualitative and quantitative analysis of diverse biotransformations. This flow-injection analysis mass spectrometry (FIA-MS) approach represents an attractive alternative to more traditional photometric, fluorometric, and chromatographic methods for screening enzymatic reactions.

Abstract

Mass spectrometry-based high-throughput screening methods combine the advantages of photometric or fluorometric assays and analytical chromatography, as they are reasonably fast (throughput ≥1 sample/min) and broadly applicable, with no need for labelled substrates or products. However, the established MS-based screening approaches require specialised and expensive hardware, which limits their broad use throughout the research community. We show that a more common instrumental platform, a single-quadrupole HPLC-MS, can be used to rapidly analyse diverse biotransformations by flow-injection mass spectrometry (FIA-MS), that is, by automated infusion of samples to the ESI-MS detector without prior chromatographic separation. Common organic buffers can be employed as internal standard for quantification, and the method provides readily validated activity and selectivity information with an analytical run time of one minute per sample. We report four application examples that cover a broad range of analyte structures and concentrations (0.1–50 mM before dilution) and diverse biocatalyst preparations (crude cell lysates and whole microbial cells). Our results establish FIA-MS as a versatile and reliable alternative to more traditional methods for screening enzymatic reactions.

Publication date: 8 June 2023

Source: Chem, Volume 9, Issue 6

Author(s): Jian-Jun Li, Jia-Hui Zhao, Hua-Chen Shen, Kevin Wu, Xin Kuang, Peng Wang, Jin-Quan Yu

Nature Synthesis, Published online: 01 May 2023; doi:10.1038/s44160-023-00294-7

High-throughput synthesis of polypeptides through ring-opening polymerization of N-carboxyanhydride is challenging. Now a diversification approach is developed based on the post-polymerization modification of a selenium-containing polypeptide. With the assistance of automation and model-guided optimization, this approach enables the discovery of functional polypeptides from chemical space with little previous knowledge.

Nature Chemistry, Published online: 01 May 2023; doi:10.1038/s41557-023-01165-6

Catalytic enantioselective approaches to access chiral organophosphorus compounds are rare. A two-stage catalytic strategy for the synthesis of diverse enantioenriched P(V) compounds has now been developed: a bifunctional iminophosphorane superbase enables enantioselective nucleophilic desymmetrization, followed by downstream enantiospecific diversification of the resulting intermediate by substitution with medicinally relevant O-, N- and S-based nucleophiles.

Biocatalytic cascades, combining the selectivity of biological systems with the elegance of chemical synthesis, offer an exceptional opportunity for the preparation of complex molecular structures. By integrating native and abiotic enzyme modules in a metabolism-like network, a five-enzyme cascade coupled with a carbonate-induced dimerization step yielded the tricyclic natural product angiopterlactone B in a two-step process.

Abstract

Nature's way to construct highly complex molecular entities as part of biosynthetic pathways is unmatched by any chemical synthesis. Yet, relying on a cascade of native enzymatic transformations to achieve a certain target structure, biosynthesis is also significantly limited in its scope. In this study, non-natural biocatalytic modules, a peroxidase-mediated Achmatowicz rearrangement and a dehydrogenase-catalyzed borrowing-hydrogen-type isomerization were successfully incorporated into an artificial metabolism, combining the benefits of traditional retrosynthesis with the elegance and efficacy of biosynthetic networks. In a highly streamlined process, the total synthesis of tricyclic angiopterlactone B was achieved in two steps operating entirely in an aqueous environment while relying mainly on enzymes as key reaction mediators.

Nitrophenolic products were selectively synthesized at 25 and 75 °C in microemulsions using stable biocatalytic magnetic beads coated with horseradish peroxidase (HRP) crosslinked in polylysine films. These nitrations gave single-products with turnover numbers on average 1.8-fold larger at 75 °C than at 25 °C.

Abstract

Enzymes as catalysts in organic syntheses can provide high regio- and stereo-selectivity, which is often not possible with chemical catalysts. Biocatalysis with iron heme enzymes has proven efficient when the enzyme is sequestered in thin films. An added feature is improved stability. For example, peroxidases chemically crosslinked in poly-lysine in films on silica nanoparticles were stable for 9 hrs or more at 90 °C, and were used for biocatalysis up to 90 °C. We show here for a series of para-substituted phenols, single nitro-phenol products can be selectively synthesized using biocatalytic magnetic beads coated with horseradish peroxidase (HRP) crosslinked in polylysine films. Nitrophenols moieties are important as synthetic intermediates and in drugs. For a series of para-substituted phenols, biocatalytic nitration gave average turnover numbers 1.8-fold larger at 75 °C than at 25 °C. For phenols giving <50 % conversion after 1 hr at 25 °C, twice the nitration yield was achieved in 1 hr at 75 °C. Results indicate that this approach should be valuable as a general tool for biocatalytic chemical synthesis.

Via regioselective oxidation, keto-saccharides can be further derivatized. Here, we show that after allylation, iodocyclization, and elimination, several methylene tetrahydrofurane-fused glycosides can be obtained. Those glycosides can be further used as scaffolds or have handles for photoclick chemistry.

Abstract

A reliable method is disclosed to introduce a fused methylene tetrahydrofuran ring into carbohydrates. The resulting bicyclic saccharides can be used as scaffolds in medicinal chemistry and drug design. In addition, the enol ether functionality serves as a handle that enables modification in biological systems via photoclick chemistry. The approach is based on the regioselective oxidation of the C-3 hydroxy group in gluco-configured pyranosides, followed by stereoselective indium-mediated allylation. The ring formation is induced by an iodocyclization reaction with a neighboring hydroxy group. Subsequent dehydrohalogenation affords the desired methylene-tetrahydrofuran-containing carbohydrates.

Chang and Perez suggest a simple and elegant approach for using AlphaFold2 to determine relative binding preferences of a receptor for two of its peptide substrates: when presented with both peptides, AlphaFold2 models only the stronger binder into the binding site. This easy approach will help many biologists to quickly estimate best binders and accelerate research on peptide substrate-mediated interactions.

Abstract

Deep learning is revolutionizing structural biology to an unprecedented extent. Spearheaded by DeepMind's Alphafold2, structural models of high quality can be generated, and are now available for most known proteins and many protein interactions. The next challenge will be to leverage this rich structural corpus to learn about binding: which protein can contact which partner(s), and at what affinity? In a recent study, Chang and Perez have presented an elegant approach towards this challenging goal for interactions that involve a short peptide binding to its receptor. The basic idea is straightforward: given a receptor that binds to two peptides, if the receptor sequence is presented with both peptides together at the same time, AlphaFold2 should model the tighter binding peptide into the binding site, while excluding the second. A simple idea that works!

Nature Communications, Published online: 27 April 2023; doi:10.1038/s41467-023-38039-x

Ebrahimi and Samanta review the key advances in the chemical and structural modification of proteins that have enabled their rise as indispensable tools in medicine and outline emerging protein engineering strategies that can potentially unlock structures with improved therapeutic properties.

Nature Synthesis, Published online: 27 April 2023; doi:10.1038/s44160-023-00293-8

Ortho-C–H and meta-C–H functionalization of arenes is well developed; however, para-C–H functionalization is more challenging. Now, a method for the synthesis of para-functionalized anilides from arylhydroxylamines and O- and S-nucleophiles is reported. The process uses fluorosulfuryl imidazolium triflates at low temperature and probably comprises O-fluorosulfonation, followed by N–O bond cleavage and nucleophilic addition.

Nature, Published online: 26 April 2023; doi:10.1038/s41586-023-05944-6

The authors report a transition-metal-catalysed protocol for recovery of polymer building block bisphenol  A and intact fibres from epoxy composites, demonstrating that chemical recycling approaches for thermoset epoxy resins and composites are achievable.