論文

Piperazine represents one of the most important building blocks of pharmaceuticals. Hence, the development of various piperazine derivatives is important. Herein we report photoinduced dehydrogenation of protected piperazines. The reaction proceeded with various alkyl-substituted piperazines. The resulting products have electron-rich olefin moieties that can react with benzyne, carbene, or acyl anhydride.

Photoinduced benzylic C-H thiocyanation is described. A series of alkyl thiocyanates were efficiently obtained by using Selectfluor as the oxidant. Moreover, we accomplished the one-pot isothiocyanation following the C-H thiocyanation. The thiocyanates and isothiocyanates were applied to the divergent transformation of pharmaceuticals.

Photoredox-catalyzed C-O bond formation reactions are reported. The decarboxylative esterification reaction allows the conversion of a variety of arylacetic acids into the corresponding benzyl carboxylates. Furthermore, the use of (diacetoxyiodo)benzene allows the conversion of the benzylic C-H bond through hydrogen atom transfer. The reactions were applied to the divergent transformation of pharmaceuticals via decarboxylative or C-H esterification reactions.

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.

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.

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.

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.

Stomatal pores in the plant epidermis open and close to regulate gas exchange between leaves and the atmosphere. Upon light stimulation, the plasma membrane (PM) H+-ATPase is phosphorylated and activated via an intracellular signal transduction pathway in stomatal guard cells, providing a primary driving force for the opening movement. To uncover and manipulate this stomatal opening pathway, we screened a chemical library and identified benzyl isothiocyanate (BITC), a Brassicales-specific metabolite, as a potent stomatal-opening inhibitor that suppresses PM H+-ATPase phosphorylation. We further developed BITC derivatives with multiple isothiocyanate groups (multi-ITCs), which demonstrate inhibitory activity on stomatal opening up to 66 times stronger, as well as a longer duration of the effect and negligible toxicity. The multi-ITC treatment inhibits plant leaf wilting in both short (1.5 h) and long-term (24 h) periods. Our research elucidates the biological function of BITC and its use as an agrochemical that confers drought tolerance on plants by suppressing stomatal opening.

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.

The direct generation of carbon radicals from carboxylic acids under visible-light photocatalysis offers an appealing strategy for molecular diversification. Here, we report a decarboxylative Giese-type addition using a zwitterionic acridinium amidate as a uniquely effective photocatalyst, which enables the efficient and selective activation and functionalization of a broad range of carboxylic acids without an external base or oxidant. The catalytic process relies on the formation of a hydrogen-bonded complex between the carboxylic acid and amidate, which triggers proton-coupled electron transfer upon photoexcitation to generate the corresponding carboxyl radical. This method featuring neutral conditions demonstrates excellent functional group tolerance and is applicable to structurally demanding substrates, including complex natural products and pharmaceutically relevant compounds.