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Stomata-small pores generally found on the leaves of plants-control gas exchange between plant and the atmosphere. Elucidating the mechanism that underlies such control through the regulation of stomatal opening/closing is important to understand how plants regulate photosynthesis and tolerate against drought. However, up-to-date, molecular components and their function involved in stomatal regulation are not fully understood. We challenged such problem through a chemical genetic approach by isolating and characterizing synthetic molecules that influence stomatal movement. Here, we describe that a small chemical collection, prepared during the development of C-H amination reactions, lead to the discovery of a Stomata Influencing Molecule (SIM); namely, a sulfonimidated oxazole that inhibits stomatal opening. The starting molecule SIM1 was initially isolated from screening of compounds that inhibit light induced opening of dayflower stomata. A range of SIM molecules were rapidly accessed using our state-of-the-art C-H amination technologies. This enabled an efficient structure-activity relationship (SAR) study, culminating in the discovery of a sulfonamidated oxazole derivative (SIM*) having higher activity and enhanced specificity against stomatal regulation. Biological assay results have shed some light on the mode of action of SIM molecules within the cell, which may ultimately lead to drought tolerance-conferring agrochemicals through the control of stomatal movement.

This study presents a new dehydrogenative synthesis of alkenyl isothiocyanates, providing compounds with bromo and isothiocyanate groups. These reactive functionalities offer versatility for further transformations. Application in an amine sensor utilizing a coumarin-attached product demonstrates practical utility. This streamlined approach facilitates access to alkenyl isothiocyanates, valuable tools for biological studies. [ABSTRACT FROM AUTHOR]

Isothiocyanates exhibit various biological characteristics, including antimicrobial, anti-inflammatory, and anticancer properties. Their significance extends to synthetic chemistry, where they serve as valuable platforms for versatile transformations. Consequently, they have attracted the attention of biologists and chemists. This review summarizes recent advancements in the synthesis of isothiocyanates. Access to a variety of starting materials is important to prepare isothiocyanates with diverse structures. This review categorizes synthetic methods into three types based on the starting materials and functional groups: (i) type A, derived from primary amines; (ii) type B, derived from other nitrogen functional groups; and (iii) type C, derived from non-nitrogen groups. Recent trends in synthetic methods have revealed the prevalence of type-A reactions derived from primary amines. However, type B reactions have rarely been reported. Notably, over the past four years, there has been a notable increase in type C reactions, indicating a growing interest in non-nitrogen-derived isothiocyanates. Overall, this review not only outlines the advancements in the synthesis of isothiocyanates but also highlights trends in the methodology. [ABSTRACT FROM AUTHOR]

Polyamines, such as putrescine and spermidine, are pivotal in various biological processes across living organisms. Despite their significance, structurally modified polyamines offer a less‐explored avenue for discovering bioactive compounds. The limitation is attributed to the synthetic difficulty of accessing functionalized polyamines. In this study, we accomplished photoredox‐catalyzed functionalization of polyamines to diversify their structure. The rapid functionalization allows attaching fluorophores to the target polyamine, facilitating the development of molecular probes for advancing chemical biology studies. [ABSTRACT FROM AUTHOR]

This article presents a study on the synthesis of primary benzylamines, which are important in medicinal chemistry. The researchers used a photoredox-catalyzed decarboxylative coupling method with aryl halides and glycine derivatives to create these molecules. They discuss the reaction mechanism and provide experimental results, including different reaction conditions and yields. This research contributes to the development of new synthetic procedures for primary benzylamine scaffolds, which could lead to the discovery of new functional molecules. Additionally, the study explores the decarboxylative aminomethylation of aryl bromides with glycine derivatives, testing various reaction conditions and catalysts to optimize product yield. The researchers found that electron-deficient aryl bromides reacted well, and the reaction was applicable to other heteroarenes. They also investigated the impact of different protecting groups on the nitrogen atom. Overall, this study offers an efficient method for synthesizing aminomethylated compounds, which may have potential applications in drug discovery. [Extracted from the article]

The discovery of new catalytic applications for metals remains an important goal in organic synthesis. If a catalyst has multiple functions, such as inducing bond cleavage and formation, it can streamline multi‐step transformations. Herein, the Cu‐catalyzed synthesis of imidazolidine through heterocyclic recombination between aziridine and diazetidine is reported. Mechanistically, Cu catalyzes the conversion of diazetidine into the corresponding imine, which then reacts with aziridine to form imidazolidine. The scope is sufficiently wide to form various imidazolidines, as many functional groups are compatible with the reaction conditions. [ABSTRACT FROM AUTHOR]

Stachyurin and casuarinin are ellagitannins, a class of polyphenols that exhibit various biological activities that have an impact on human health. Casuarinin is a stachyurin stereoisomer. These compounds contain the characteristic C‐glycosidic bond between the open‐chain d‐glucose and the phenol aromatic ring. Therefore, chemical elucidation of the C‐glycosidic bond reactivity is required to exploit their multiple bioactivities. This study developed a method for the divergent synthesis of stachyurin and casuarinin via the α‐selective C‐glycosylation as well as the β‐selective introduction of the oxygen functional group, focusing on structural specificity. The proposed method applies to the syntheses of stachyurin and casuarinin analogues, thereby facilitating the utilisation of their beneficial bioactivities. [ABSTRACT FROM AUTHOR]

Arylcarbazoles have been widely used in materials science as important organic semiconductor molecules. To investigate the electronic and photophysical properties of arylcarbazole with different substitution patterns, facile and straightforward synthesis of arylcarbazole derivatives is sought after. Herein we report on photo‐induced direct arylation reactions of carbazole. Treatment of carbazoles with aryldiazonium salts afforded the arylated carbazole. Although the reaction was not regioselective, C1 and C4‐arylated carbazoles were obtained as the major isomers. When N‐pyridylcarbazole was employed as the substrate with palladium catalyst, the reaction proceeded selectively at C1 position. [ABSTRACT FROM AUTHOR]

The article titled "Functionalized Polyamine Synthesis with Photoredox Catalysis" discusses the challenges in accessing modified polyamines and their potential for discovering bioactive compounds. The cover image illustrates the use of catalysts irradiated by light to facilitate the rapid functionalization of target polyamines, allowing for the attachment of various substituents. This process can lead to the development of novel bioactive molecules and molecular probes for chemical biology studies. The research article by K. Murakami and co-workers provides more detailed information on this topic. [Extracted from the article]

Polycyclic aromatic hydrocarbons (PAHs) represent an emerging class of π‐conjugated molecules in the area of optoelectronic devices and materials. Unprecedented synthetic routes to various PAHs from simple phenol derivatives by a palladium‐catalyzed annulative dimerization of phenylene triflate through twofold inter‐ and intramolecular C−H activation have been established. The initially formed partially fused PAHs can be smoothly transformed into a variety of fully fused PAHs by the Scholl reaction. Furthermore, the reactions of phenanthrene‐substituted aryl triflates proceeded regioselectively. The findings inspired the development of a rapid and efficient synthesis of polybenzoacene derivatives. This study not only allows transformation of phenyl triflates, but also discloses a new retrosynthetic strategy towards PAHs, especially polybenzoacenes. [ABSTRACT FROM AUTHOR]

Rhodium-catalyzed regioselective arylzincation of terminal allenes is performed to obtain synthetically useful functionalized allylzinc reagents. The obtained allylzinc reagents react with a variety of electrophiles such as acetonitrile to offer a more versatile three-component coupling reaction.

The zinc-catalyzed nucleophilic substitution reaction of chlorosilanes with organomagnesium reagents is reported. The reaction provides a mild and efficient method for the large scale preparation of functionalized tetraorganosilanes.

2,2′‐Bipyridyls have been utilized as indispensable ligands in metal‐catalyzed reactions. The most streamlined approach for the synthesis of 2,2′‐bipyridyls is the dehydrogenative dimerization of unfunctionalized pyridine. Herein, we report on the palladium‐catalyzed dehydrogenative synthesis of 2,2′‐bipyridyl derivatives. The Pd catalysis effectively works with an AgI salt as the oxidant in the presence of pivalic acid. A variety of pyridines regioselectively react at the C2‐positions. This dimerization method is applicable for challenging substrates such as sterically hindered 3‐substituted pyridines, where the pyridines regioselectively react at the C2‐position. This reaction enables the concise synthesis of twisted 3,3′‐disubstituted‐2,2′‐bipyridyls as an underdeveloped class of ligands. [ABSTRACT FROM AUTHOR]

Facile synthesis of fluorinated benzofurans from polyfluorophenols has been accomplished by means of a sigmatropic dearomatization/defluorination strategy composed of three processes: (1) interrupted Pummerer reaction of ketene dithioacetal monoxides with polyfluorophenols followed by [3,3] sigmatropic rearrangement, (2) Zn‐mediated smooth reductive removal of fluoride from the dearomatized intermediate, and (3) acid‐promoted cyclization/aromatization. Mechanistic investigations revealed important characteristic reactivity of polyfluorophenols in the present system. Some of the fluorinated benzofuran products were transformed by utilizing the 2‐methylsulfanyl moieties. Facile synthesis of fluorinated benzofurans from polyfluorophenols has been accomplished by means of a sigmatropic dearomatization/defluorination strategy composed of three processes: interrupted Pummerer reaction followed by [3,3] sigmatropic rearrangement, Zn‐mediated smooth reductive removal of fluoride from the dearomatized intermediate, and acid‐promoted cyclization/aromatization. [ABSTRACT FROM AUTHOR]

Abstract: A photoredox‐catalyzed decarboxylative oxidation of arylacetic acids, which are privileged scaffolds in pharmaceuticals, is reported herein. The established method is operationally simple and a variety of substrates are applicable, providing rapid access to dehomologated bioisosteres of common pharmaceuticals. [ABSTRACT FROM AUTHOR]

Abstract: Amino group is one of the most ubiquitous functional groups, and therefore the direct introduction of amino groups into arenes has gained much attention. Methods for installing amino groups into organic molecules are highly sought after. Herein, a direct C−H imidation under gold(I) chloride catalysis has been developed with N‐fluorobenzenesulfonimide as the imine source. The choice of ligand plays an important role where 2,2′‐biquinoline was found to be most efficient. Various polycyclic aromatic hydrocarbons were directly imidated under the newly established protocol. [ABSTRACT FROM AUTHOR]

Abstract: The rapid transformation of pharmaceuticals and agrochemicals enables access to unexplored chemical space and thus has accelerated the discovery of novel bioactive molecules. Because arylacetic acids are regarded as key structures in bioactive compounds, new transformations of these structures could contribute to drug/agrochemical discovery and chemical biology. This work reports carbon–nitrogen and carbon–oxygen bond formation through the photoredox‐catalyzed decarboxylation of arylacetic acids. The reaction shows good functional group compatibility without pre‐activation of the nitrogen‐ or oxygen‐based coupling partners. Under similar reaction conditions, carbon–chlorine bond formation was also feasible. This efficient derivatization of arylacetic acids makes it possible to synthesize pharmaceutical analogues and bioconjugates of pharmaceuticals and natural products. [ABSTRACT FROM AUTHOR]

Azines, which are six-membered aromatic compounds containing one or more nitrogen atoms, serve as ubiquitous structural cores of aromatic species with important applications in biological and materials sciences. Among a variety of synthetic approaches toward azines, C-H functionalization represents the most rapid and atom-economical transformation, and it is advantageous for the late-stage functionalization of azine-containing functional molecules. Since azines have several C-H bonds with different reactivities, the development of new reactions that allow for the functionalization of azines in a regioselective fashion has comprised a central issue. This review describes recent advances in the C-H functionalization of azines categorized as follows: (1) SNAr reactions, (2) radical reactions, (3) deprotonation/functionalization, and (4) metal-catalyzed reactions. [ABSTRACT FROM AUTHOR]

Dibenzothiophene dioxides, which are readily prepared through oxidation of the parent dibenzothiophenes, undergo nucleophilic aromatic substitution with anilines intermolecularly and then intramolecularly to yield the corresponding carbazoles in a single operation. The 'aromatic metamorphosis' of dibenzothiophenes into carbazoles does not require any heavy metals. This strategy is also applicable to the synthesis of indoles. Since electron-deficient thiaarene dioxides exhibit interesting reactivity, which is not observed for that the corresponding electron-rich azaarenes, a combination of a thiaarene-dioxide-specific reaction with the SNAr-based aromatic metamorphosis allows transition-metal-free construction of difficult-to-prepare carbazoles. [ABSTRACT FROM AUTHOR]

NiCl2(PPh3)(IPr) catalyzes cross-coupling reactions of 2-methylsulfanylbenzofurans with alkyl Grignard reagents. Other nickel complexes such as NiCl2(dppe) failed to catalyze the same reaction. The alkylation is applicable to the synthesis of a couple of protein tyrosine phosphatase inhibitors, 3-(4-biphenylyl)-2-alkylbenzofurans. [ABSTRACT FROM AUTHOR]

The palladium-catalyzed silylation of aryl chlorides with silylsilatranes proceeds under activator-free conditions; hence, wide functional group compatibility is displayed and boryl and siloxy groups are able to survive. Experimental and computational studies revealed that smooth transmetalation from the silylsilatrane to the arylpalladium chloride is facilitated by strong interaction between the Lewis acidic silicon and the chloride. [ABSTRACT FROM AUTHOR]

Cross-coupling of general aryl alkyl sulfides with arylzinc reagents proceeds smoothly, even at room temperature or below, with a palladium-N-heterocyclic carbene (NHC) catalyst. When combined with reactions that are unique to organosulfurs, that is, the SNAr sulfanylation or Pummerer reaction, the cross-coupling offers interesting transformations that are otherwise difficult to achieve. An alkylsulfanyl group is preferentially converted whilst leaving the tosyloxy and chloro intact, which expands the variety of orthogonal cross-coupling. [ABSTRACT FROM AUTHOR]

A combination of a palladium-NHC catalyst and potassium hexamethyldisilazide enables the amination of aryl sulfides with anilines to afford a wide variety of diarylamines. The reaction conditions are versatile enough for the reaction of even bulky ortho-substituted aryl sulfides. This amination can be applied to the modular synthesis of N-aryl carbazoles from the corresponding ortho-bromothioanisoles. As aryl sulfoxides undergo extended Pummerer reactions to afford ortho-substituted aryl sulfides, the Pummerer products are thus useful substrates for the amination to culminate in efficient syntheses of a 2-anilinobenzothiophene and an indole as proof-of-principle of the utility of the extended Pummerer reaction/amination cascade. [ABSTRACT FROM AUTHOR]

Operationally simple, efficient, and widely applicable Pummerer annulations of simple phenols with ketene dithioacetal monoxides, with the aid of trifluoroacetic anhydride, have been shown to provide a variety of benzofurans having a methylthio group at the 2-position. Subsequent and newly developed nickel-catalyzed arylation at the methylthio group culminates in diversity-oriented synthesis of multisubstituted benzofurans. Our extended Pummerer annulation/cross-coupling sequence is powerful enough to synthesize biologically active natural products as well as highly fluorescent benzofuran derivatives. [ABSTRACT FROM AUTHOR]

Caffeine, a common ingredient in energy drinks, crosses the blood–brain barrier easily, but the kinetics of caffeine across the blood–cerebrospinal fluid barrier (BCSFB) has not been investigated. Therefore, 127 autopsy cases (Group A, 30 patients, stimulant-detected group; and Group B, 97 patients, no stimulant detected group) were examined. In addition, a BCSFB model was constructed using human vascular endothelial cells and human choroid plexus epithelial cells separated by a filter, and the kinetics of caffeine in the BCSFB and the effects of 4-aminopyridine (4-AP), a neuroexcitatory agent, were studied. Caffeine concentrations in right heart blood (Rs) and cerebrospinal fluid (CSF) were compared in the autopsy cases: caffeine concentrations were higher in Rs than CSF in Group A compared to Group B. In the BCSFB model, caffeine and 4-AP were added to the upper layer, and the concentration in the lower layer of choroid plexus epithelial cells was measured. The CSF caffeine concentration was suppressed, depending on the 4-AP concentration. Histomorphological examination suggested that choroid plexus epithelial cells were involved in inhibiting the efflux of caffeine to the CSF. Thus, the simultaneous presence of stimulants and caffeine inhibits caffeine transfer across the BCSFB. [ABSTRACT FROM AUTHOR]

Novel transformations of metal porphyrins, such as nickel, zinc, copper, and silver porphyrins, to magnesium porphyrins are described. The reactions were accomplished by using 4‐methylphenylmagnesium bromide in toluene. The scope of the reactions was wide and various magnesium porphyrins were obtained (see figure). The products, acid‐sensitive magnesium porphyrins, were smoothly converted to free‐base porphyrins under weakly acidic conditions. [ABSTRACT FROM AUTHOR]

The first examples of metal-catalyzed extended Pummerer reactions through the activation of sulfoxides are described. The copper-catalyzed reactions of ketene dithioacetal monoxides with alkynyl sulfides and ynamides provided a wide variety of γ,γ-disulfanyl-β,γ-unsaturated carbonyl compounds with an accompanying oxygen rearrangement. The products can be easily converted into 1,4-dicarbonyl compounds and substituted heteroaromatics. DFT calculations and mechanistic experiments revealed a new interesting stepwise addition/oxygen rearrangement mechanism. [ABSTRACT FROM AUTHOR]

In Ca2+-free medium, propylene glycol (PG) increases the cytosolic-free Ca2+ concentration ([Ca2+]i) in rat cerebrocortical synaptosomes. In the current studies, the authors investigated the intracellular source of this Ca2+. PG (0.5-5% v/v) dose-dependently increased [Ca2+]i in Ca2+-free medium. The increase in [Ca2+]i was completely inhibited by pretreatment with the mitochondrial uncoupler, carbonylcyanide m-chlorophenylhydrazone (CCCP, 10 µM). The inhibitory effect of CCCP was dependent on the concentration and the pretreatment time. These results suggest that, in Ca2+-free medium, PG increases [Ca2+]i in rat cerebrocortical synaptosomes by releasing Ca2+ from mitochondrial stores. [ABSTRACT FROM AUTHOR]

In these studies, the authors investigated the effect of propylene glycol (PG) on the cytosolic free Ca2+ concentration ([Ca2+]i) in rat cerebrocortical synaptosomes using the fluorescent Ca2+ indicator fura-2. PG (0.5-5% v/v) increased [Ca2+]i in a concentration-dependent manner. The PGinduced increase in [Ca2+]i was inhibited approximately 50% by the omission of extracellular Ca2+ or the addition of Ni2+ (100 µM). Decrease of extracellular Na+ (6.2 mM) or addition of tetrodotoxin (1 µM), verapamil (10 µM), nifedipine (10 µM), ω-agatoxin IVA (200 nM), ωconotoxin GVIA (1 µM), or ω-conotoxin MVIIC (1 µM) had no effect on the increase in [Ca2+]i. Also, addition of TMB-8 (100 µM), ryanodine (50 µM) or thapsigargin (1 µM) did not modify the increase in [Ca2+]i in the absence of extracellular Ca2+. These results suggest that PG increases [Ca2+]i in rat cerebrocortical synaptosomes by both stimulating Ca2+ entry through a Ni2+-sensitive pathway and releasing Ca2+ from TMB8-, ryanodine- and thapsigargin-insensitive Ca2+ stores. [ABSTRACT FROM AUTHOR]