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Protein lipidation dynamically controls protein localization and function within cellular membranes. A unique form of protein O-fatty acylation in Corynebacterium, termed protein O-mycoloylation, involves the attachment of mycolic acids─unusually large and hydrophobic fatty acids─to serine residues of proteins in these organisms outer mycomembrane. However, as with other forms of protein lipidation, the scope and functional consequences of protein O-mycoloylation are challenging to investigate due to the inherent difficulties of enriching and analyzing lipidated peptides. To facilitate the analysis of protein lipidation and enable the comprehensive profiling and site mapping of protein O-mycoloylation, we developed a chemical proteomics strategy integrating metabolic labeling, click chemistry, cleavable linkers, and a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method employing LC separation and complementary fragmentation methods tailored to the analysis of lipophilic, MS-labile O-acylated peptides. Using these tools in the model organism Corynebacterium glutamicum, we identified approximately 30 candidate O-mycoloylated proteins, including porins, mycoloyltransferases, secreted hydrolases, and other proteins with cell envelope-related functions─consistent with a role for O-mycoloylation in targeting proteins to the mycomembrane. Site mapping revealed that many of the proteins contained multiple spatially proximal modification sites, which occurred predominantly at serine residues surrounded by conformationally flexible peptide motifs. Overall, this study (i) discloses the putative protein O-mycoloylome for the first time, (ii) yields new insights into the undercharacterized proteome of the mycomembrane, which is a hallmark of important pathogens (e.g., Corynebacterium diphtheriae, Mycobacterium tuberculosis), and (iii) provides generally applicable chemical strategies for the proteomic analysis of protein lipidation.

Methods to access chiral sulfur(VI) pharmacophores are of interest in medicinal and synthetic chemistry. We report the desymmetrization of unprotected sulfonimidamides via asymmetric acylation with a cinchona-phosphinate catalyst. The desired products are formed in excellent yield and enantioselectivity with no observed bis-acylation. A data-science-driven approach to substrate scope evaluation was coupled to high throughput experimentation (HTE) to facilitate statistical modeling in order to inform mechanistic studies. Reaction kinetics, catalyst structural studies, and density functional theory (DFT) transition state analysis elucidated the turnover-limiting step to be the collapse of the tetrahedral intermediate and provided key insights into the catalyst-substrate structure-activity relationships responsible for the origin of the enantioselectivity. This study offers a reliable method for accessing enantioenriched sulfonimidamides to propel their application as pharmacophores and serves as an example of the mechanistic insight that can be gleaned from integrating data science and traditional physical organic techniques.

A series of α-hydroxy-alkylphosphonates and α-hydroxy-alkylphosphine oxides were synthesized by the Pudovik reaction of acetaldehyde and acetone with dialkyl phosphites or diarylphosphine oxides. The additions were performed in three different ways: in liquid phase using triethylamine as the catalyst (1), on the surface of Al2O3/KF solid catalyst (2), or by a MW-assisted Na2CO3-catalyzed procedure (3). In most of the cases, our methods were more efficient and more robust than those applied in the literature. Two of the α-hydroxy-alkylphosphonates were subjected to single-crystal X-ray analysis, suggesting a dimeric and a chain supramolecular buildup in their respective crystals. Four α-hydroxy-alkylphosphonates and one α-hydroxy-ethylphosphine oxide were reacted with different acid chlorides to afford ten α-acyloxyphosphonates. Diethyl α-hydroxy-ethylphosphonate was transformed to the methanesulfonyloxy derivative that was useful in the Michaelis–Arbuzov reaction with triethyl phosphite and ethyl diphenylphosphinite to afford tetraethyl ethylidenebisphosphonate and diethyl α-(diphenylphosphinoyl)-ethylphosphonate, respectively. The α-hydroxyphosphonates and α-hydroxyphosphine oxides prepared were subjected to bioactivity studies, and the compounds tested exhibited limited cytotoxic effects on U266 cells with modest reductions in viability at a concentration of 100 μM. [ABSTRACT FROM AUTHOR]

We propose here that acylation modification of actinomycete proteins is a restrictive system that limits the excessive synthesis of secondary metabolites, its mechanism has not been clearly elucidated before. We used crotonylation as an example to investigate the acylation effect in the daptomycin biosynthesis by Streptomyces roseosporus. Our experiments revealed abundant crotonylation of numerous secondary metabolic enzymes in Streptomyces roseosporus, a daptomycin producer. DptE, which initiates daptomycin biosynthesis, is crotonylated at K454. We experimentally identified the corresponding DptE crotonyltransferase Kct1 and decrotonylase CobB. Further studies consistently confirmed that decrotonylation increases DptE activity. Decrotonylation functions like loosening a faucet knob, increasing substrate channel throughput and the initial flow of daptomycin biosynthesis. Moreover, DptE catalytic activity was enhanced via K454 and neighboring residues K184 and Q420 mutation, increasing daptomycin yield by 132%; daptomycin biosynthesis related metabolism activities also increased. Substrate channel prediction revealed 38% higher throughput for mutant DptE (K454I/K184Q/Q420N) than crotonylated DptE. Molecular dynamics (MD) simulations revealed significant increases in flexibility and substrate affinity of the mutant. In summary, we elucidated the faucet knob effect of DptE crotonylation on the initial flow of daptomycin biosynthesis and adopted decrotonylation to generate high-yield industrial strains. • Enzymes and regulators involved in Streptomyces roseosporus SM biosynthesis are crotonylated abundantly. • Identification of DptE crotonylation and its crotonyltransferase/decrotonylase. • Decrotonylation of DptE increases its substrate throughput, rising initial metabolic flow for daptomycin biosynthesis. • Engineering of DptE increases daptomycin yield by 132% and improves overall metabolic activity of Sreptomyces roseosporus. • Protein acylation may play a common role in restricting secondary metabolite biosynthesis in Streptomyces. [ABSTRACT FROM AUTHOR]

Acylation represents a pivotal biochemical process that is instrumental in the modification of secondary metabolites throughout the growth and developmental stages of plants. The BAHD acyltransferase family within the plant kingdom predominantly utilizes coenzyme A thioester as the acyl donor, while employing alcohol or amine compounds as the acceptor substrates to facilitate acylation reactions. Using bioinformatics approaches, the LjBAHD gene family members in the genome of Leonurus japonicus (L. japonicus) were identified and characterized including gene structure, conserved motifs, cis -acting elements, and potential gene functions. To elucidate the roles of BAHD genes in various tissues of L. japonicus , the expression profiles of LjBAHD family members across different organs were scrutinized. Under drought stress treatment, some LjBAHDs were upregulation, suggesting their potential involvement in drought response. Notably, a detailed study was conducted on a specific HCT gene (i.e., LjBAHD 25) within the BAHD gene family. Analysis of its expression patterns suggested a role for LjBAHD 25 in the phenylpropanoid metabolism pathway in L. japonicus , contributing to the biosynthesis of secondary metabolites with unique bioactivity. The findings of this study have established a scientific foundation for the subsequent development and functional validation of the BAHD gene family in L. japonicus. [ABSTRACT FROM AUTHOR]

The document titled "Green Chemistry" published by the Royal Society of Chemistry in 2024 showcases cutting-edge research for a greener, sustainable future. It includes critical reviews, tutorial reviews, communications, and papers on various topics such as CO2 switchable solvents, photo- and electro-chemical synthesis, and green synthesis of aromatic aldehydes. The journal aims to connect the world with chemical sciences and invest profits back into the chemistry community, emphasizing interdisciplinary science to preserve the environment. [Extracted from the article]

The CdS/Mg–Fe layered double hydroxide (LDH) was successfully constructed by coupling CdS and Mg–Fe LDH based on the mutually complementary properties of the two materials. This stable and recyclable heterogeneous photocatalyst was found to realize the C3-acylation of indoles with α-keto acids. The reactions were carried out under irradiation with blue light at room temperature using abundant and inexpensive air as the oxidant. This methodology gives easy access to 3-acyl indoles with high yields. CdS/Mg–Fe LDH can be recovered and reused for multiple runs without obviously losing its photocatalytic activity. [ABSTRACT FROM AUTHOR]

Both preventing the production of waste and achieving high atom economy are fundamental principles of green chemistry. Herein, the first example of a 100% atom economical construction of hydroxyalkylated N-heteroarenes, done through recyclable decatungstate-photocatalyzed tandem cyclization/self-hydrogenation of isocyanides with equimolar amounts of aldehydes without exogenous hydrogen reagent and under byproduct-free conditions, was developed. Mechanistic studies revealed that three sequential hydrogen atom transfer processes might be involved in this reaction and all the leaving hydrogens as hydrogen sources were incorporated into the target hydroxyalkylated products. [ABSTRACT FROM AUTHOR]

RNAs fold into compact structures and undergo protein interactions in cells. These occluded environments can block reagents that probe the underlying RNAs. Probes that can analyze structure in crowded settings can shed light on RNA biology. Here, we employ 2′-OH-reactive probes that are small enough to access folded RNA structure underlying close molecular contacts within cells, providing considerably broader coverage for intracellular RNA structural analysis. The data are analyzed first with well-characterized human ribosomal RNAs and then applied transcriptome-wide to polyadenylated transcripts. The smallest probe acetylimidazole (AcIm) yields 80% greater structural coverage than larger conventional reagent NAIN3, providing enhanced structural information in hundreds of transcripts. The acetyl probe also provides superior signals for identifying m6A modification sites in transcripts, particularly in sites that are inaccessible to a standard probe. Our strategy enables profiling RNA infrastructure, enhancing analysis of transcriptome structure, modification, and intracellular interactions, especially in spatially crowded settings. [Display omitted] • Probing methods map structures of intracellular RNAs obscured by close contacts • The smallest probing agent provide missing structural data with 80% greater coverage • The probing tools provide superior signals for identifying m6A modification sites The cellular function of RNA is intimately linked to its structure. The 3D structure of RNA is intricate and compact, and is often complexed with other macromolecules for regulatory interaction. These interactions frequently lead to occluded environments that block structure probing by current reagents. Our study establishes a strategy for mapping and analyzing RNA infrastructure with close spatial contacts in living cells, comparing standard acylating probes to small-sized probes for the assessment of the regions where RNAs are closely interacting with proteins and nearby RNAs. The small AcIm probe shows substantially greater structural probing ability in both human and bacteria ribosomal RNAs underlying cellular contexts. In addition to the greater coverage of RNA folding information, the comparative analysis of small and standard probes can also help to infer distances and tunnel spaces of nucleotides close to nearby macromolecules. Applying the RNA infrastructure profiling strategy transcriptome-wide, our data reveals ca. 80% more structural information for polyadenylated transcripts. In addition, RNA infrastructure analysis with small reagent AcIm reveals pronounced signals for m6A methylation sites of RNAs in their native cellular setting, even in spatially crowded environments. Our approach could help to deepen the understanding of the underlying mechanisms for RNA biology, both by providing considerably greater secondary structure mapping coverage, and by providing information about close protein/RNA or RNA/RNA contacts. For instance, mRNA structures can influence protein interactions, thereby regulating gene expression through various mechanisms such as altering post-transcriptional modifications, exposing specific sequences or forming specific structural motifs. 1,2 By detecting mRNA structures and modifications, our study could help to elucidate the intricate relationship between RNA structure and cellular translation, shedding light on how mRNA structures impact protein interactions. A further interesting example may exist within biological condensates, which represent a broad class of crowded cellular environments formed by multivalent interactions between proteins and RNAs, playing critical roles in regulating diverse cellular processes. 3,4 Despite their importance, the differential structures and interactions of RNAs within these condensates remain largely unknown. Profiling RNA secondary structures and inferring distance of interactions within these compact compartments could provide insights into the molecular mechanisms underlying condensate functions, thus advancing our understanding of RNA roles in cellular processes. Xiao et al. employed small and standard 2′-OH-reactive probes to study intracellular RNA structures underlying close molecular contacts, revealing considerably broader coverage for RNA structural analysis and superior signals for m6A sites identification in transcripts. This strategy provides insights into RNA infrastructure and interactions in spatially crowded settings. [ABSTRACT FROM AUTHOR]

Anthocyanins have attracted a lot of attention in the fields of natural pigments, food packaging, and functional foods due to their color, antioxidant, and nutraceutical properties. However, the poor chemical stability and low bioavailability of anthocyanins currently limit their application in the food industry. Various methods can be used to modify the structure of anthocyanins and thus improve their stability and bioavailability characteristics under food processing, storage, and gastrointestinal conditions. This paper aims to review in vitro modification methods for altering the molecular structure of anthocyanins, as well as their resulting improved properties such as color, stability, solubility, and antioxidant properties, and functional applications as pigments, sensors and functional foods. In industrial production, by mixing co-pigments with anthocyanins in food systems, the color and stability of anthocyanins can be improved by using non-covalent co-pigmentation. By acylation of fatty acids and aromatic acids with anthocyanins before incorporation into food systems, the surface activity of anthocyanins can be activated and their antioxidant and bioactivity can be improved. Various other chemical modification methods, such as methylation, glycosylation, and the formation of pyranoanthocyanins, can also be utilized to tailor the molecular properties of anthocyanins expanding their range of applications in the food industry. [ABSTRACT FROM AUTHOR]

In continuation of our commitment to the synthesis of new ring systems based on the 6,11‐dihydrodibenzo[c,f][1,2]thiazepine 5,5‐dioxide core of the antidepressant drug tianeptine, we have incorporated two‐ and/or three‐carbon bridges between the nitrogen atom of the sulfonamide moiety and the N‐, O‐ or S‐substituent at position 11 of the tricycle. The synthesis of 5 new ring systems is described and demonstrated with several target compounds. [ABSTRACT FROM AUTHOR]

The high value‐added utilization of the fluorinated silica slag (FSS) waste, an associated by‐product of the anhydrous HF production from the accompanying fluorine resources in phosphate ore, is of great importance, but it remains a challenge. In this work, the Mg modified and unmodified Hβ zeolites from FSS waste were successfully prepared by a green dry gel conversion crystallization method with tetraethylammonium hydroxide (TEAOH) as a structure‐directing agent (SDA). The in situ Mg modified Hβ zeolite (Mg−Hβ) shows much superior catalytic performance to unmodified (Hβ) and post Mg‐modified Hβ (Mg/Hβ) zeolites for acetylation of 2‐methoxynaphthalene (2‐MN) to 6‐acetyl‐2‐methoxynaphthalene (2,6‐AcMN), and the 40.2 % of conversion for 2‐MN with 66.3 % of selectivity for 2,6‐AcMN were achieved, ascribed to the high amount of B acidic sites and the promoted shape‐selective catalysis effect by higher surface area and volume of micropores. This work not only opens a new avenue for the high value‐added utilization of fluorinated silica slag waste, but also generates an efficient solid acid catalyst for the clean production of 2,6‐AcMN through the acetylation of 2‐MN with acetic anhydride. [ABSTRACT FROM AUTHOR]

This study investigates the transesterification of isoflavones puerarin and β-D-fructofuranosyl-(2→6)-puerarin to enhance their lipophilicity for specific pharmacological applications. The process achieved high yields (80-100%) in the isoflavones conversion when commercial lipases from Candida antarctica (CALB) and Thermomyces lanuginosus (TL IM) were used. The acylation patterns between CALB and TL IM varied depending on the substrate; both enzymes yielded principally monoacylated products from puerarin and β-D-fructofuranosyl-(2→6)-puerarin. However, TL IM also produced di- and triacylated derivatives of β-D-fructofuranosyl-(2→6)-puerarin in substantial amounts. Structural characterization by NMR identified puerarin-6ʹʹ-O-laurate and β-D-fructofuranosyl-(2→6)-puerarin-6ʹʹʹ-O-laurate as the primary products in CALB and TL IM reactions. These acyl derivatives presented improved lipophilicity (Log P from −1.0 − 0.16 to 3.26 − 3.58) and antioxidant activity (67.2-97.3 to 102.5-131.4 µM TE/mmol). Therefore, these compounds have potential pharmacological applications. [ABSTRACT FROM AUTHOR]

A series of usnic acid derivatives containing a thiazole ring with an amide substituent were synthesized. The convenient method for synthesis of these compounds is a reaction of 14-bromousnic acid with N-acylthioureas. Acylation of aminothiazole does not lead to the targeted compound. [ABSTRACT FROM AUTHOR]

Phosphine‐mediated one‐pot reactions have been developed that involve two mechanistically distinct reactions assembled in one reaction vessel via the sequential addition process. The first step involves MBH‐type annulation of α,β‐ynones to afford cyclic products in each case, which then engages in subsequent β‐acylation or intramolecular Wittig reactions. The reaction conditions are mild and efficient, providing acylated alkylidene indandiones in 70%–99% yields or furo[2,3‐f]dibenzotropones in 65%–91% yields, respectively. [ABSTRACT FROM AUTHOR]

A variety of 1-(1,4-dihydroxynaphtalen-2-yl) ketones was synthesized using the photo-Friedel–Crafts acylation of 1,4-naphthoquinone with aldehydes. Subsequent oxidation using silver oxide readily furnished the corresponding 2-acylated 1,4 naphthoquinones. Notably, these naphthoquinone derivatives underwent spontaneous partial reduction upon storage. The synthesized compounds were subjected to antimicrobial screening. High inhibition effects on Staphylococcus aureus were found for the majority of compounds, which makes them interesting for potential future medicinal applications. [ABSTRACT FROM AUTHOR]

A simple ortho‐acylation of 4‐phenylquinazoline by a Pd‐catalyzed oxidative C−H activation was developed, with moderate yields, in which no prefunctionalized methylarenes were used as acylation reagents. Moreover, this methodology tolerates a wide range of functional groups. Radical scavenging experiments indicate that the acylation involves a benzoyl radical pathway. [ABSTRACT FROM AUTHOR]

A photoinduced copper‐catalyzed enantioselective conjugate addition of acylsilanes has been developed. The conjugate acylation of α,β‐unsaturated ketones and aldehydes was promoted by a copper(I)/chiral NHC catalyst under visible‐light irradiation for synthesizing various 2‐substituted 1,4‐dicarbonyl compounds in enantioenriched forms. Mechanistic studies combining experiments and quantum chemical calculations indicated a reaction mechanism involving copper‐to‐acyl charge transfer (i. e. metal‐to‐ligand charge transfer (MLCT)) excitation of an alkene‐bound acylcopper complex. The MLCT excitation is followed by an electronical and geometrical change to generate a triplet β‐radical‐C‐enolate‐Cu(II)‐acyl complex with an acyl radical character, which undergoes facile excited state C−C bond formation in the copper coordination sphere, affording the 1,4‐conjugate addition product. [ABSTRACT FROM AUTHOR]

A methodology was developed for synthesizing N -acyl- N '-sulfonyl hydrazides through acyl substitution reactions between activated amides and arylsulfonyl hydrazides. Optimization of the reaction conditions revealed that using Cs₂CO₃ as a base and 1,4-dioxane as a solvent at 25 °C for 12 hours produced the highest yields. Among various amides tested, N -benzoylsuccinimide was found to be the most reactive, with reduced reactivity observed for N -mesityl-, N -tosyl-, and N -Boc-substituted tertiary benzoyl amides. Cross-reactions between a diverse range of N -benzoylsuccinimides and arylsulfonyl hydrazides successfully produced the corresponding N -acyl- N′ -sulfonyl hydrazides with yields ranging from 63% to 94%. [ABSTRACT FROM AUTHOR]

The increasing interest in axially chiral biaryl moieties, which are prevalent in chiral ligands, organocatalysts, and bioactive molecules, has raised the need for developing novel efficient synthetic methods for these types of molecules. In addition to the currently available methods, such as kinetic resolution, desymmetrization and enantio‐ and diastereo‐selective biaryl coupling, we herein report a lipase‐catalyzed dynamic kinetic resolution (DKR) of racemic 2‐hydroxybiaryls through enantioselective O‐acylation. This method features the production of enantiomerically enriched atropisomers (89 %–98 % ee) in 91 %–99 % yields from eleven racemates. Notably, the DKR proceeds without any racemization catalyst since in situ‐racemization was achieved by easy rotation about the biaryl axis of the substrates. The enzymatic O‐acylation then furnished conformationally stable biaryl‐containing esters, in which the increased steric bulkiness of the O‐acyl moiety suppresses the rotation, i. e., racemization, under the reaction conditions of 35–50 °C. This experimental study was accompanied by a computational determination of the rotational barrier of substrates and products. The choice of suitable substrates with a significant difference in their rotational barrier compared to that of their products turned out to be the key to an efficient implementation of this method. [ABSTRACT FROM AUTHOR]

We describe the use of acyl imidazoles derived from aliphatic carboxylic acids for the N-heterocyclic carbene/organic photoredox co-catalyzed meta -selective functionalization of electron-rich arenes. Compared to our previous work, a change of the wavelength of the applied LED light from 440 nm to 390 nm promotes this reaction efficiently. [ABSTRACT FROM AUTHOR]

Acylation of azepano-11-deoxoglycyrrhetol synthesized N-acetyl- and N,O-bis-acetyl derivatives. The structure of azepano-11-deoxoglycyrrhetol was confirmed by an XSA. Data for its influence on cell cycle progression suggested that suppression of cell survival was due primarily to a cytostatic effect that was related to arrest of the S or G1 phase, depending on the cell line. [ABSTRACT FROM AUTHOR]

A series of seven new meso -phenyl BODIPY-pyrrolo[3,4- b ]pyridin-5-one conjugates were synthesized in one experimental step by using a Sc(III)-catalyzed Ugi-Zhu three-component reaction coupled to a cascade sequence (aza Diels-Alder/ N -acylation/aromatization) as post-MCR functionalization process. Further experimental studies were performed behind understanding the fluorescence response toward viscosity. All compounds exhibited a linear response between increasing viscosity (DMSO and glycerol mixtures) and fluorescence intensity. The different substituents also influenced the photophysical properties. Furthermore, in DMSO all compounds exhibited dual emission. Each band is attributed to the pyrrolo[3,4- b ]pyridin-5-one and BODIPY moieties, respectively. The electronic structure of all compounds was computed by DFT and TD-DFT calculations, allowing to determine the molecular orbitals involved in the electronic transitions. [ABSTRACT FROM AUTHOR]

The selection of quality excipients is a crucial step in peptide formulation development. Apart from excipient incompatibility, process-related impurities or degradants of an excipient can interact with peptide-active pharmaceutical ingredients, forming the interaction products. The formaldehyde has been reported as an impurity of excipient in polyethylene glycol, glycerol, magnesium stearate, microcrystalline cellulose, mannitol, etc. The peptide contains various amino acids such as histidine, lysine, and arginine having free amine groups. These amine groups act as strong nucleophile and can increase the reactivity of peptides. PLGA is the most widely used biodegradable polymer in sustained-release formulations. The hydrolysis of PLGA generates glycolic acid and lactic acid impurities, which can form the interaction product with the amines of peptides. During the formulation development of Liraglutide, we have found few interaction products. The systematic characterization and mechanistic understanding of these interaction products lead us to imidazopyrimidine, glycolyl, and lactolyl moieties. These interaction products have been characterized thoroughly with the use of LC-HRMS, MS/MS, and hydrogen-deuterium exchange mass studies. The study revealed that the reactivity of N-terminal histidine must be considered for formulation development. Moreover, the quality of excipients with respect to presence of impurities must be considered as critical material attributes. [ABSTRACT FROM AUTHOR]

Abstract Aldehyde dehydrogenases (ALDHs) represent a superfamily of enzymes, which oxidize aldehydes to the corresponding acids. Certain families, namely ALDH9 and ALDH10, are best active with ω-aminoaldehydes arising from the metabolism of polyamines such as 3-aminopropionaldehyde and 4-aminobutyraldehyde. Plant ALDH10s show broad specificity and accept many different aldehydes (aliphatic, aromatic and heterocyclic) as substrates. This work involved the above-mentioned aminoaldehydes acylated with dicarboxylic acids, phenylalanine, and tyrosine. The resulting products were then examined with native ALDH10 from pea and recombinant ALDH7s from pea and maize. This investigation aimed to find a common efficient substrate for the two plant ALDH families. One of the best natural substrates of ALDH7s is aminoadipic semialdehyde carrying a carboxylic group opposite the aldehyde group. The substrate properties of the new compounds were demonstrated by mass spectrometry of the reaction mixtures, spectrophotometric assays and molecular docking. The N-carboxyacyl derivatives were good substrates of pea ALDH10 but were only weakly oxidized by the two plant ALDH7s. The N-phenylalanyl and N-tyrosyl derivatives of 3-aminopropionaldehyde were good substrates of pea and maize ALDH7. Particularly the former compound was converted very efficiently (based on the k cat/K m ratio), but it was only weakly oxidized by pea ALDH10. Although no compound exhibited the same level of substrate properties for both ALDH families, we show that these enzymes may possess more common substrates than expected.

Acyl iodides are expected to be excellent acylating agents due to the low bond dissociation energy of the carbon–iodine bond and the high capability of iodine as a leaving group. Unfortunately, the preparative methods for acyl iodides directly from carboxylic acids are rather limited. In this work, we found that a novel binary system combining I2 and diphenylphosphine oxide (Ph2P(O)H) provides a simple method for the preparation of acyl iodides from carboxylic acids. Furthermore, the subsequent one‐pot reaction with appropriate nucleophiles, such as amines, alcohols, and thiols, afforded the corresponding amides, esters, and thioesters, respectively, in good to excellent yields. [ABSTRACT FROM AUTHOR]

4-Methyl-6-pyrazolyl-2-chloronicotinonitriles were synthesized by the reaction of 6-hydrazino-4-methyl-2-chloronicotinonitriles with 1,3-diketones. Upon treatment with hydrazine and methylhydrazine, 4-methyl-6-pyrazolyl-2-chloronicotinonitriles were converted into the corresponding 3-amino-4-methyl-6-pyrazolyl-1H-pyrazolo[3,4-b]pyridines. A similar reaction involving 1,1-dimethylhydrazine and ethylhydrazine was accompanied by elimination of the alkyl substituent and also led to the formation of 3-amino-6-pyrazolyl-1H-pyrazolo[3,4-b]pyridines. Acylation and carbamoylation of the prepared compounds proceeded regioselectively at the amino group. One of the new compounds, N-[6-(3,5-dimethylpyrazol-1-yl)-1,4-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanoylamide, showed a growth-stimulating effect in the field experiments on winter wheat crops. [ABSTRACT FROM AUTHOR]

The homolysis of chemical bonds represents one of the most fundamental reactivities of excited molecules. Historically, it has been exploited to generate radicals under ultraviolet (UV) light irradiation. However, unlike most contemporary radical‐generating mechanisms, the direct excitation to homolyze chemical bonds and produce aliphatic carbon‐centered radicals under visible light remains rare, especially in metallaphotoredox cross couplings. Herein, we present our design of the dihydropyrimidoquinolinone (DHPQ) reagents derived from ketones, which can undergo formal deacylation and homolytic C−C bond cleavage to release alkyl radicals without external photocatalysts. Spectroscopic and computational analysis reveal unique optical and structural features of DHPQs, rationalizing their faster kinetics in alkyl radical generation than a structurally similar but visible‐light transparent radical precursor. Such a capability allows DHPQ to facilitate a wide range of Ni‐metallaphotoredox cross couplings with aryl, alkynyl and acyl halides. Other catalytic and non‐catalyzed alkylative transformations of DHPQs are also feasible with various radical acceptors. We believe this work would be of broad interest, aiding the synthetic planning with simplified operation and expanding the synthetic reach of photocatalyst‐free approaches in cutting‐edge research. [ABSTRACT FROM AUTHOR]

The document is the contents list for an issue of the journal Chemical Communications. It includes the titles and authors of various articles and communications related to chemistry research. Topics covered include the potential of MOF-based single-atom photocatalysts, anion-exchange membrane electrolyzers for hydrogen production, and progress on lithium-sulfur batteries. The journal is published by The Royal Society of Chemistry, a leading chemistry community. [Extracted from the article]

This short review article demonstrates recent techniques for the typical conversion of adamantyl C(sp3)−Br bond to various C−C, C−N, and C−X bonds enabled by multiple conditions and reagents with the use of organometallic reagents. This work mainly focuses on developing a mild and convenient system for the selective preparation of substituted adamantyl zinc and magnesium reagents (Ad‐MX) bearing different functional groups on the adamantyl framework. The adamantane scaffolds were selectively functionalized using a various of catalytic methods, most likely organometallic‐Zn, Mg reagent‐mediated Negishi cross‐coupling reactions, acylation, arylation, thiolation, 1,2/1,4‐addition, alkynylation, amination, halogenation, and allylation, etc. Over the years adamantyl derivatives have been broadly studied in various medicinal applications, drug development, supramolecular chemistry, material science, and nanotechnologies, etc. [ABSTRACT FROM AUTHOR]

We report the first switchable acylation of H-phosphonate with chloroformate. The acylation site (P vs. O) in H-phosphonate was switched by changing the acyl pyridinium/ammonium ions. Unexpected phosphite formation was observed during the O-acylation of H-phosphonate. Twenty-six structurally diverse phosphotriesters and phosphonoformate esters were synthesized in microflow reactors. [ABSTRACT FROM AUTHOR]

Enhancing the hydrophobicity of chitosan through acylation enables the encapsulation of water‐insoluble drugs within the polymeric carrier cores. In this study, hydrophobically modified chitosan was synthesized by reacting low‐molecular‐weight chitosan with acyl chloride (C18–C24) using an agitation method under mild conditions. The structure of acylated chitosan was analyzed using FTIR and 1H‐NMR spectroscopy. The degree of substitution (DS) varied between 56% and 69% for different long‐chain N‐acylated chitosan, with N‐stearoyl chitosan (ChC18) exhibiting the highest DS. The incorporation of capecitabine (CAP) into extended acylated chitosan increased particle size and decreased zeta potential. N‐lignoceroyl chitosan (ChC24) exhibited the highest zeta potential value of −27 mV for 0.2 mg of CAP, indicating that the most extended acyl group was the most stable in the suspension. Transmission electron microscope images revealed that all acylated chitosan particles were spherical, with sizes ranging from 100 to 200 nm, and existed as stand‐alone entities, indicating excellent stability in suspension. The loading of CAP increased in particle size but did not alter particle shape, except for ChC24, which exhibited agglomeration. SEM images revealed that the individual arrangement of particles in CAP‐ChC18 made it more stable than other acylated chitosan. In contrast, the formation of clusters in CAP‐ChC24 can be attributed to strong hydrophobic interactions. X‐ray photoelectron spectroscopy results show that there is no nitrogen atom in ChC18, which means that the acyl group is oriented inward and bound to the stearoyl group via van der Waals forces. At different drug weight‐to‐carrier ratios, the encapsulation efficiency (EE) of CAP with varying acyl group lengths ranged from 85% to 97%. The drug loading (DL) capacity and EE increased as the amount of drug in the carrier increased. However, the length of the acyl group did not significantly affect DL and EE, even when the carrier‐to‐drug ratio was consistently maintained. Sustained release was observed in CAP‐loaded ChC24, indicating a significant influence of the extended chain on chitosan. Consequently, extended N‐acylated chitosan possesses enormous potential as a drug delivery system for CAP. [ABSTRACT FROM AUTHOR]

Twenty 3-acyloxymaltol/ethyl maltol derivatives (7a-j and 8a-j) were synthesized and evaluated in vitro for their anti-oomycete activity against Phytophthora capsici, respectively. Among all of twenty derivatives, more than half of the compounds 7f, 7h, 8a-h and 8j had anti-oomycete activity higher than the positive control zoxamide (EC50 = 22.23 mg/L), and the EC50 values of 18.66, 20.32, 12.80, 16.18, 10.59, 14.98, 16.80, 10.36, 15.32, 12.64, and 13.59 mg/L, respectively. Especially, compounds 8c and 8f exhibited the best anti-oomycete activity against P. capsici with EC50 values of 10.59 and 10.36 mg/L, respectively. Overall, hydroxyl group of maltol/ethyl maltol is important active modification site. [ABSTRACT FROM AUTHOR]

A series of N-isonicotinoyl-3(5)-ferrocenyl-5(3)-substituted 1H-pyrazoles was obtained as the mixtures of the products by acylation of tautomeric forms of 3-ferrocenyl-5-substituted 1H-pyrazoles with isonicotinoyl chloride. The rate of hydrolysis of the synthesized compounds depended on the electronic effects of the substituents in the pyrazole ring and increased in the following order Me < Ph ≈ COOEt ≪ CF3. The hydrolysis rate of the synthesized compounds in acidic medium is significantly higher than under neutral conditions, which is associated with the possibility of the redistribution of electron density in the aromatic pyrazole ring upon the pyrazole protonation. The revealed regularities can be used for designing the redox and pH sensors, acylating agents, and antituberculosis agents active against isoniazid-resistant mycobacterium strains. [ABSTRACT FROM AUTHOR]

Metal triflate-catalyzed acylation of sulfonamides and direct transacylation of N-acylsulfonamides have been investigated. The acylation of sulfonamides proceeds efficiently in the presence of a catalytic amount of Cu(OTf)2 (0.001 equiv) using either carboxylic anhydrides or acyl chlorides as the acylating agents. Alternative catalysts suitable for this transformation include Al(OTf)3, Fe(OTf)3, Ga(OTf)3, In(OTf)3, and Er(OTf)3. In the presence of Cu(OTf)2 (0.2 equiv), N-acylsulfonamides undergo direct transacylation in excess acyl chlorides (10 equiv) to furnish new N-acylsulfonamides through exchange of N-acyl groups. Ga(OTf)3, Fe(OTf)3, and In(OTf)3 are similarly reactive in catalyzing such transacylation transformations. The reaction conditions are mild and operationally convenient. A variety of functional groups including halogeno, keto, nitro, cyano, ether, and carboxylic ester are tolerated, providing the corresponding monoacylated N-acylsulfonamides in good to excellent yields. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Phthalides serve as core structures pervasive in a wide array of natural products and drug molecules, which display a diverse array of biological activities. We report herein a highly efficient dynamic kinetic resolution of 3‐hydroxyphthalides by chiral isothioureas (ITUs) catalyzed asymmetric acylation, facilitating the effective synthesis of a variety of chiral phthalidyl esters with good yields and enantioselectivities. Notably, this reaction features mild reaction conditions, expansive substrate scope as well as good functional group compatibility. In addition, the practicality of this method is underscored by the large‐scale synthesis, reduced catalyst loading experiment and the synthesis of the chiral phthalidyl ester prodrug. [ABSTRACT FROM AUTHOR]

Carbohydrates are synthetically challenging molecules with vital biological roles in all living systems. To better understand the biological functions of this fundamentally important class of molecules, novel methodologies are needed, including site-selective functionalization and glycosylation reactions. This account describes our efforts toward the development of novel methodologies for site-selective functionalization of carbohydrates and stereoselective glycosylation through various acylation reactions. [ABSTRACT FROM AUTHOR]

NLRP3 is an inflammasome seeding pattern recognition receptor activated in response to multiple danger signals which perturb intracellular homeostasis. Electrostatic interac- tions between the NLRP3 polybasic (PB) region and negatively charged lipids on the trans-Golgi network (TGN) have been proposed to recruit NLRP3 to the TGN. In this study, we demonstrate that membrane association of NLRP3 is critically dependant on S-acylation of a highly conserved cysteine residue (Cys-130), which traps NLRP3 in a dynamic S-acylation cycle at the Golgi, and a series of hydrophobic residues preceding Cys-130 which act in conjunction with the PB region to facilitate Cys-130 dependent Golgi enrichment. Due to segregation from Golgi localised thio- esterase enzymes caused by a nigericin induced breakdown in Golgi organisation and function, NLRP3 becomes immobilised on the Golgi through reduced de-acylation of its Cys-130 lipid anchor, suggesting that disruptions in Golgi homeostasis are conveyed to NLRP3 through its acylation state. Thus, our work defines a nigericin sensitive S-acylation cycle that gates access of NLRP3 to the Golgi. [ABSTRACT FROM AUTHOR]

The present review discusses the development of new metal‐free conditions for the hydroacylation of alkenes and alkynes under both thermal and photochemical conditions from 2018, and their application to the synthesis of various bioactive molecules over the past few years. The key point highlights the remarkable progress made by metal‐free catalytic systems in comparison to the conventional metal catalysts in the hydroacylation of alkenes, alkynes, and arenes. Both inter‐ and intramolecular hydroacylation reactions and their mechanistic pathways were discussed. The most current developments in the synthesis of several natural, pharmaceutical, and heterocyclic compounds using hydroacylation reactions have also been introduced. [ABSTRACT FROM AUTHOR]

Tyrosol and hydroxytyrosol are powerful phenolic antioxidants occurring in olive oil and in by-products from olive processing. Due to their high polarity, esterification or other lipophilization is necessary to make them compatible with lipid matrices. Hydroxytyrosol methyl carbonate is a more effective antioxidant than dibutylhydroxytoluene or α-tocopherol and together with tyrosol methyl carbonate exerts interesting pharmacological properties. The purpose of this work was the enzymatic preparation of alkyl carbonates of tyrosol and hydroxytyrosol. A set of 17 hydrolases was tested in the catalysis of tyrosol methoxycarbonylation in neat dimethyl carbonate to find an economically feasible alternative to the recently reported synthesis of methyl carbonates catalyzed by Novozym 435. Novozym 435 was, however, found to be the best performing catalyst, while Novozym 735, pig pancreatic lipase, lipase F-AK and Lipex 100T exhibited limited reactivity. No enzyme accepted 1,2-propylene carbonate as the acylation donor. Under optimized reaction conditions, Novozym 435 was used in the batch preparation of tyrosol methyl carbonate and hydroxytyrosol methyl carbonate in quantitative yields. The enzymatic methoxycarbonylation of tyrosol and hydroxytyrosol can also be used as a method for their selective protection in enzymatic syntheses of phenylethanoid glycosides catalyzed with enzymes comprising high levels of acetyl esterase side activity. [ABSTRACT FROM AUTHOR]

A general and highly enantioselective method for the preparation of tetra‐substituted 3‐hydroxyphthalide esters via isothiourea‐catalysed acylative dynamic kinetic resolution (DKR) is reported. Using (2S,3R)‐HyperBTM (5 mol %) as the catalyst, the scope and limitations of this methodology have been extensively probed, with high enantioselectivity and good to excellent yields observed (>40 examples, up to 99 %, 99 : 1 er). Substitution of the aromatic core within the 3‐hydroxyphthalide skeleton, as well as aliphatic and aromatic substitution at C(3), is readily tolerated. A diverse range of anhydrides, including those from bioactive and pharmaceutically relevant acids, can also be used. The high enantioselectivity observed in this DKR process has been probed computationally, with a key substrate heteroatom donor O⋅⋅⋅acyl‐isothiouronium interaction identified through DFT analysis as necessary for enantiodiscrimination. [ABSTRACT FROM AUTHOR]

The development of methods to allow the selective acylative dynamic kinetic resolution (DKR) of tetra‐substituted lactols is a recognised synthetic challenge. In this manuscript, a highly enantioselective isothiourea‐catalysed acylative DKR of tetra‐substituted morpholinone and benzoxazinone‐derived lactols is reported. The scope and limitations of this methodology have been developed, with high enantioselectivity and good to excellent yields (up to 89 %, 99 : 1 er) observed across a broad range of substrate derivatives incorporating substitution at N(4) and C(2), di‐ and spirocyclic substitution at C(5) and C(6), as well as benzannulation (>35 examples in total). The DKR process is amenable to scale‐up on a 1 g laboratory scale. The factors leading to high selectivity in this DKR process have been probed through computation, with an N−C=O⋅⋅⋅isothiouronium interaction identified as key to producing ester products in highly enantioenriched form. [ABSTRACT FROM AUTHOR]

The strategy for the preparation of polyisobutylene‐based block copolymers via mechanistic transformation from cationic to radical polymerization is reported. This strategy involves the synthesis of 2‐bromo‐2‐methylpropanoyl‐terminated difunctional polyisobutylene macroinitiator (BiBB‐PIB‐BiBB) via consecutive cationic polymerization, in situ preparation of hydroxyl‐terminated polyisobutylene and its acylation by 2‐bromo‐2‐methylpropanoyl bromide. The Mn2(CO)10−triggered photo‐induced radical polymerization of styrene in bulk using this macroinitiator leads to the formation of multiblock copolymer, while predominantly triblock copolymer is generated during the polymerization of methyl methacrylate. The possibility to functionalize the polyisobutylene by pyrene via photo‐induced radical addition of 1‐bromomethyl pyrene in the presence of Mn2(CO)10 is also demonstrated in this work. [ABSTRACT FROM AUTHOR]

This work includes the synthesis of new pyrazoline derivatives 5-13 over three steps starting from 1,3-indandione. The first step included the acylation of 1,3- indandione with acetyl chloride to produce compound 1 with excellent yield (90%). In the second step, the enolate form of 1 was condensed with various aromatic aldehydes (benzaldehyde, p-nitrobenzaldehyde, and p-chlorobenzaldehyde) to afford the corresponding α,β-unsaturated carbonyl derivatives 2-4 in high yields (93-95%). The third step involved a reaction of 2-4 with hydrazine hydrate, phenyl hydrazine, and p-nitrophenyl hydrazine to give the desired pyrazoline derivatives 5-13 in yields ranging from 70 to 83%. The structure of the synthesized compounds was verified through FT-IR and 1H NMR spectroscopy. Additionally, a subset of the synthesized compounds underwent testing to evaluate their antibacterial and antioxidant properties. [ABSTRACT FROM AUTHOR]

The cross‐regulation of immunity and metabolism is currently a research hotspot in life sciences and immunology. Metabolic immunology plays an important role in cutting‐edge fields such as metabolic regulatory mechanisms in immune cell development and function, and metabolic targets and immune‐related disease pathways. Protein post‐translational modification (PTM) is a key epigenetic mechanism that regulates various biological processes and highlights metabolite functions. Currently, more than 400 PTM types have been identified to affect the functions of several proteins. Among these, metabolic PTMs, particularly various newly identified histone or non‐histone acylation modifications, can effectively regulate various functions, processes and diseases of the immune system, as well as immune‐related diseases. Thus, drugs aimed at targeted acylation modification can have substantial therapeutic potential in regulating immunity, indicating a new direction for further clinical translational research. This review summarises the characteristics and functions of seven novel lysine acylation modifications, including succinylation, S‐palmitoylation, lactylation, crotonylation, 2‐hydroxyisobutyrylation, β‐hydroxybutyrylation and malonylation, and their association with immunity, thereby providing valuable references for the diagnosis and treatment of immune disorders associated with new acylation modifications. [ABSTRACT FROM AUTHOR]

The novel Schiff bases 3a-d were synthesized by reacting 6-methyl--2-aminobenzothiazole and different substituted benzaldehydes. Afterwards, the obtained Schiff bases were reduced with NaBH4 to form amine compounds 4a-d. In the final step, reaction of the amine with chloroacetyl chloride gave the novel amide derivatives 5a-d. The structures of the all novel synthesized compounds were characterized by FT-IR, ¹H-NMR, 13C-NMR, ESI MS, HETCOR, 2D (¹H-¹H) COSY spectra and elemental analyses. The antimicrobial activities of the novel synthesized compounds, were tested against some Gram-positive and Gram-negative bacterial as well as fungal species and the results were discussed. [ABSTRACT FROM AUTHOR]