Abstract: The development of synthetic strategies for the preparation of bioisosteric compounds is a demanding undertaking in medicinal chemistry. Numerous strategies have been developed for the synthesis of bicyclo[1.1.1]pentanes (BCPs), bridge-substituted BCPs, and bicyclo[2.1.1]hexanes. However, progress on the synthesis of bicyclo[3.1.1]heptanes, which serve as meta-substituted arene bioisosteres, has not been previously explored. Herein, we disclose the first photoinduced [3σ + 2σ] cycloaddition for the synthesis of trisubstituted bicyclo[3.1.1]heptanes using bicyclo[1.1.0]butanes and cyclopropylamines. This transformation not only uses mild and operationally simple conditions but also provides unique meta-substituted arene bioisosteres. The applicability of this method is showcased by simple derivatization reactions.

Abstract: Diacids are important monomers in the polymer industry to construct valuable materials. Dicarboxylation of unsaturated bonds, such as alkenes and alkynes, with CO2 has been demonstrated as a promising synthetic method. However, dicarboxylation of C─C single bonds with CO2 has rarely been investigated. Herein we report a novel electrochemical ring-opening dicarboxylation of C─C single bonds in strained rings with CO2. Structurally diverse glutaric acid and adipic acid derivatives were synthesized from substituted cyclopropanes and cyclobutanes in moderate to high yields. In contrast to oxidative ring openings, this is also the first realization of an electroreductive ring-opening reaction of strained rings, including commercialized ones. Control experiments suggested that radical anions and carbanions might be the key intermediates in this reaction. Moreover, this process features high step and atom economy, mild reaction conditions (1 atm, room temperature), good chemoselectivity and functional group tolerance, low electrolyte concentration, and easy derivatization of the products. Furthermore, we conducted polymerization of the corresponding diesters with diols to obtain a potential UV-shielding material with a self-healing function and a fluorine-containing polyester, whose performance tests showed promising applications.

Abstract: Carbon-hydrogen (C−H) functionalization of pyridines is a powerful tool for the rapid construction and derivatization of many agrochemicals, pharmaceuticals, and materials. Because of the inherent electronic properties of pyridines, selective meta-C−H functionalization is challenging. Here, we present a protocol for highly regioselective meta-C−H trifluoromethylation, perfluoroalkylation, chlorination, bromination, iodination, nitration, sulfanylation, and selenylation of pyridines through a redox-neutral dearomatization-rearomatization process. The introduced dearomative activation mode provides a diversification platform for meta-selective reactions on pyridines and other azaarenes through radical as well as ionic pathways. The broad scope and high selectivity of these catalyst-free reactions render these processes applicable for late-stage functionalization of drugs. Description Activating pyridine’s 3-position Numerous pharmaceutical compounds contain aromatic heterocycle components such as pyridine. Chemists therefore prize reactions that selectively append substituents to particular sites on these rings. Boyle et al. report that upon opening pyridine rings to form linear imines, the distinct characteristics of these intermediates strongly favored halogenation at the carbon in the otherwise unreactive 3-position. Recyclization then yielded a selectively halogenated ring. A complementary approach by Cao et al. relies on a reversible reaction of the pyridines with an alkyne and ester, disrupting the electronic structure to activate the 3-position for halogenation as well as trifluoromethylation (see the Perspective by Joo). —JSY Opening and reclosing pyridines enables selective halogenation at the 3-position of the ring.

Abstract: Since its development in 2006, dispersive liquid-liquid microextraction has witnessed many improvements in the design of extraction devices, extractant dispersion strategies, choice of extraction and dispersive solvents, and phase separation approaches. It has also been combined with other extraction techniques to extend its application to more complicated matrices. Many developments have been made concerning simultaneous derivatization, entire procedure automation, and coupling with analytical instrumentation. The main objective of these changes was to resolve a certain issue with the existing design or procedure or make the extraction process and analysis relatively easier, faster, or greener. This review aims to provide an overview of the evolution of DLLME over the years and highlights the scenarios where different formats can be applied, and their advantages and limitations have been critically appraised.

Abstract: Selective functionalization of aliphatic C-H bonds, ubiquitous in molecular structures, could allow ready access to diverse chemical products. While enzymatic oxygenation of C-H bonds is well established, the analogous enzymatic nitrogen functionalization is still unknown; nature is reliant on preoxidized compounds for nitrogen incorporation. Likewise, synthetic methods for selective nitrogen derivatization of unbiased C-H bonds remain elusive. In this work, new-to-nature heme-containing nitrene transferases were used as starting points for the directed evolution of enzymes to selectively aminate and amidate unactivated C(sp3)-H sites. The desymmetrization of methyl- and ethylcyclohexane with divergent site selectivity is offered as demonstration. The evolved enzymes in these lineages are highly promiscuous and show activity toward a wide array of substrates, providing a foundation for further evolution of nitrene transferase function. Computational studies and kinetic isotope effects (KIEs) are consistent with a stepwise radical pathway involving an irreversible, enantiodetermining hydrogen atom transfer (HAT), followed by a lower-barrier diastereoselectivity-determining radical rebound step. In-enzyme molecular dynamics (MD) simulations reveal a predominantly hydrophobic pocket with favorable dispersion interactions with the substrate. By offering a direct path from saturated precursors, these enzymes present a new biochemical logic for accessing nitrogen-containing compounds.

Abstract: Hyaluronan, the extracellular matrix glycosaminoglycan, is an important structural component of many tissues playing a critical role in a variety of biological contexts. This makes hyaluronan, which can be biotechnologically produced in large scale, an attractive starting polymer for chemical modifications. This review provides a broad overview of different synthesis strategies used for modulating the biological as well as material properties of this polysaccharide. We discuss current advances and challenges of derivatization reactions targeting the primary and secondary hydroxyl groups or carboxylic acid groups and the N-acetyl groups after deamidation. In addition, we give examples for approaches using hyaluronan as biomedical polymer matrix and consequences of chemical modifications on the interaction of hyaluronan with cells via receptor-mediated signaling. Collectively, hyaluronan derivatives play a significant role in biomedical research and applications indicating the great promise for future innovative therapies.

Abstract: White jellyfungus is one of the most popular nutritional supplements. The polysaccharide (WJP) is an important active component of White jellyfungus, it not only has a variety of biological activities but also is nontoxic to humans. So, many scholars have carried out different research on WJP. However, the lack of a detailed summary of WJP limits the scale of industrial development of WJP. Herein, the research progress of WJP in extraction, isolation, structure, derivatization, and structure–activity relationship was reviewed. Different extraction methods were compared, the activity and application of WJP were summarized, and the structure–activity relationship of WJP was emphasized to provide effective theoretical support for improving the utilization of WJP and promoting the application of related industries.

Abstract: By applying the aroma extract dilution analysis, 13 esters were found to have high FD factors in the Laobaigan flavor type of Baijiu. These were then quantified using GC-MS. In addition, 35 nonvolatile organic acids were quantified by a derivatization method combined with GC-MS. The perceptual interactions of lactic acid and ethyl lactate and that of lactic acid and ethyl acetate were studied through the olfactory threshold. The S curve was used to evaluate the changes in the olfactory thresholds. After adding lactic acid (1142, 20 000, and 53 703 mg/L), the olfactory thresholds of ethyl lactate (1000, 724, and 295 mg/L) and ethyl acetate (398, 324, and 257 mg/L) decreased obviously, which revealed that lactic acid gave additive or synergistic odor effects for the two esters. Furthermore, it was discovered that as the concentrations of lactic acid increased, the extent of the interaction among these compounds was also greater in the mixture.

Abstract: The polysaccharide from Morinda citrifolia fermentation liquor was extracted by the hot water method. The acetylated polysaccharide, phosphorylated polysaccharide, carboxymethylated polysaccharide, and sulfated polysaccharide were identified by IR and NMR spectra. The results showed that Morinda citrifolia polysaccharide and its derivatives showed the good antioxidant activity, and them up to Vc level. These results provide a good basis for studying the antioxidant activity and structural‐activity relationship of Morinda citrifolia polysaccharide and its derivatives.

Abstract: Steroids are compounds widely available in nature and synthesized for therapeutic and medical purposes. Although several analytical techniques are available for the quantification of steroids, their analysis is challenging due to their low levels and complex matrices of the samples. The efficiency and quick separation of the HPLC combined with the sensitivity, selectivity, simplicity, and cost-efficiency of fluorescence, make HPLC coupled to fluorescence detection (HPLC-FLD) an ideal tool for routine measurement and detection of steroids. In this review, we covered HPLC-FLD methods reported in the literature for the steroids quantification in clinical, pharmaceutical, and environmental applications, focusing on the various approaches of fluorescent derivatization. The aspects related to analytical methodology including sample preparation, derivatization reagents, and chromatographic conditions will be discussed.

Abstract: Abstract Fundamental to the synthesis of enantioenriched chiral molecules is the ability to assign absolute configuration at each stereogenic center, and to determine the enantiomeric excess for each compound. While determination of enantiomeric excess and absolute configuration is often considered routine in many facets of asymmetric synthesis, the same determinations for enantioisotopomers remains a formidable challenge. Here, we report the first highly enantioselective metal‐catalyzed synthesis of enantioisotopomers that are chiral by virtue of deuterium substitution along with the first general spectroscopic technique for assignment of the absolute configuration and quantitative determination of the enantiomeric excess of isotopically chiral molecules. Chiral tag rotational spectroscopy uses noncovalent chiral derivatization, which eliminates the possibility of racemization during derivatization, to perform the chiral analysis without the need of reference samples of the enantioisotopomer.

Abstract: An accurate analysis of the composition of stable isotopes is today an increasingly important requirement in various fields of science (from the environmental to the medical field). Since 2004, the year of its introduction on the market, Liquid Chromatography coupled with Isotope Ratio Mass Spectrometry (LC-IRMS) has expanded the applications possible with the most famous and widespread Elemental Analyzer (EA) and Gas Chromatography Combustion (GC-C)-IRMS techniques. The new liquid chromatography interface coupled with IRMS opened to new application areas, in particular by enabling compound-specific δ13C analysis of non-volatile, water-soluble compounds from complex mixtures. The advantages of the technique include the possibility of performing a compound-specific analysis without altering isotopic signatures by derivatization. Applications in paleoarchaeology, nutrition and trophic, pediatrics, soil science and food authenticity are examined here by reporting on the progress and technical constraints.

Abstract: The instrumental analysis of complex mixtures of sugars often requires derivatization to enhance the method’s selectivity and sensitivity. 1-Phenyl-3-methyl-5-pyrazolone (PMP) is a common sugar derivatization agent used in high-performance liquid chromatography (HPLC). Although many C18 column applications for PMP–sugar derivative analysis have been developed, their transferability is not straightforward due to variations in column chemistry and preparation technology. The aim of this study was to develop and validate an application for Zorbax Extend C18 columns for the analysis of 8 neutral and 2 acidic sugars commonly found in plant polysaccharides. The method was further compared to well-established alditol acetates and m-hydroxydiphenyl methods and employed for sugar profiling of selected agro-industrial wastes. The most influential separation factors were the mobile-phase pH and acetonitrile content, optimized at 8.0 and a 12–17% gradient, respectively. The method showed excellent linearity, repeatability and intermediate precision. High sensitivity was achieved, especially for neutral sugars, with an accuracy error range of 5–10% relative standard deviation. The sugar profiling results were highly correlated to the reference method for neutral sugars. The HPLC method was highly applicable for the evaluation of polysaccharides in selected wastes and showed advantages in terms of simplicity, accuracy in acidic sugar determination and suitability for their simultaneous analysis with neutral sugars.

Abstract: Heterocycles are the backbone of modern medical chemistry and drug development. The derivatization of "an olefin" inside aromatic rings represents an ideal approach to access functionalized saturated heterocycles from abundant aromatic building blocks. Here, we report an operationally simple, efficient, and practical method to selectively access hydrosilylated and reduced N-heterocycles from bicyclic aromatics via a key diradical intermediate. This approach is expected to facilitate complex heterocycle functionalizations that enable access to novel medicinally relevant scaffolds.

Abstract: This Feature focuses on a review of recent developments in mass spectrometry imaging (MSI) of lipid isomers in biological tissues. The tandem MS techniques utilizing online and offline chemical derivatization procedures, ion activation techniques such as ozone-induced dissociation (OzID), ultraviolet photodissociation (UVPD), or electron-induced dissociation (EID), and other techniques such as coupling of ion mobility with MSI are discussed. The importance of resolving lipid isomers in diseases is highlighted.