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N-glycosides comprise a broad range of compounds, some of which have demonstrated a variety of bioactivities, such as antiviral, antitumor, and antibacterial activities. Serving as essential building blocks for DNA and RNA, nucleosides are a particularly important subclass of N-glycosides. Accordingly, natural N-glycosides and their analogs have garnered great interests of both organic and pharmaceutical chemists, who have developed numerous synthetic methods for the preparation of N-glycosides. By reviewing the natural N-glycosides published between 1980 and 2023, this article summarizes current strategies for synthesizing N-glycosides, aiming to provide support for the development and research of N-glycosides.

To find potential type III secretion system (T3SS) inhibitors against citrus canker caused by Xanthomonas citrisubsp. citri(Xcc), a new series of 5-phenyl-2-furan carboxylic acid derivatives stitched with 2-mercapto-1,3,4-thiadiazole were designed and synthesized. Among the 30 compounds synthesized, 14 compounds significantly inhibited the promoter activity of a harpin gene hpa1.Eight of the 14 compounds did not affect the growth of Xcc, but significantly reduced the hypersensitive response (HR) of tobacco and decreased the pathogenicity of Xccon citrus plants. Subsequent studies have demonstrated that these inhibitory molecules effectively suppress the T3SS of Xccand significantly impair the pathogen’s ability to subvert citrus immunity, resulting in a reduction in the level of disease progression. As a result, our work has identified a series of potentially attractive agents for the control of citrus canker.

Agrochemical science prioritizes the discovery and effective synthesis of innovative and promising lead compounds. Herein, we developed an efficient column chromatography-free synthesis for β-carboline 1-hydrazides via a mild CuBr2-catalyzed oxidation and investigated the antifungal and antibacterial activities and mechanisms for these compounds. In our study, compounds 4de(EC50= 0.23 μg·mL–1) and 4dq(EC50= 0.11 μg·mL–1) displayed the best efficacy, demonstrating enhancements in inhibitory activity of more than 20-fold against Ggtcompared to silthiopham (EC50= 2.39 μg·mL–1). Additionally, compound 4de(EC50= 0.21 μg·mL–1) demonstrated outstanding in vitroantifungal activities as well as in vivocurative activities against Fg. According to preliminary mechanistic studies, β-carboline 1-hydrazides led to the accumulation of reactive oxygen species, destruction of cell membranes, and dysregulation of histone acetylation. Furthermore, several substances exhibited antibacterial activity against Psgand Cmsby preventing the development of bacterial biofilms.

Nitrogen-centered radicals are versatile synthetic intermediates with the ability to undergo diverse reactions such as hydrogen atom transfer (HAT), β-scission, and addition across unsaturated systems. A long-standing impediment to the wider adoption of these intermediates in synthesis has been the difficulty of their generation. Herein we disclose a new hydrazonyl carboxylic acid precursor to nitrogen-centered radicals and its application toward remote C–H fluorination and chlorination reactions of sulfonyl-protected alkyl amines via 1,5-HAT.

The development of C–H activation reactions that use inexpensive and practical oxidants remains a significant challenge. Until our recent disclosure of the β-lactonization of free aliphatic acids, the use of peroxides in C–H activation reactions directed by weakly coordinating native functional groups was unreported. Herein, we report C(sp3)–H β-acetoxylation and γ-, δ-, and ε-lactonization reactions of free carboxylic acids enabled by a novel cyclopentane-based mono-N-protected β-amino acid ligand. Notably, tert-butyl hydrogen peroxide is used as the sole oxidant for these reactions. This reaction has several key advantages over other C–H activation protocols: (1) exclusive monoselectivity was observed in the presence of two α-methyl groups; (2) aliphatic carboxylic acids containing α-hydrogens are compatible with this protocol; (3) lactonization of free acids, affording γ-, δ-, or ε-lactones, has been achieved for the first time.

Alkoxy radicals have long been known to enable remote C–H functionalization via 1,5-hydrogen atom abstraction. However, methods for their generation traditionally have relied upon highly oxidizing metals, ultraviolet radiation, or preformed peroxide intermediates, which has prevented the development of many desirable transformations. Herein we report a new bench-stable precursor that decomposes to free alkoxy radicals via a previously unreported single-electron oxidation pathway. This new precursor enables the fluorination and chlorination of remote C–H bonds under exceptionally mild conditions with exceedingly high monoselectivity. Iterative use of this precursor enables the introduction of a second halogen atom, granting access to remote dihalide motifs, including CF2and CFCl.

Ligand-enabled Pd-catalyzed regioselective α,β-dehydrogenation of carbonyl compounds via β-methylene C–H activation has recently emerged as a promising transformation. Herein, we report the realization of β,γ-dehydrogenation and subsequent vinyl C–H olefination reactions of free carboxylic acids, thus providing a unique method for the structural diversification of aliphatic acids containing α-quaternary centers through sequential functionalizations of two β-C–H bonds and one γ-C–H bond. This tandem dehydrogenation–olefination–lactonization reaction offers a one-step preparation of β-alkylidene-γ-lactones, which are often difficult to prepare through conventional methods, from inexpensive and abundant free aliphatic acids. A variety of free aliphatic acids, such as isosteviol and grandiflorolic acid natural products, and olefins are compatible with the reported protocol. The newly designed bidentate oxime ether-pyridone and morpholine-pyridone ligands are crucial for this tandem reaction to proceed. Notably, these ligands also enable preferential methylene C–H activation over the previously reported, competing process of methyl C–H bond olefination.

The development of practical C–H/C–H coupling reactions remains a challenging yet appealing synthetic venture because it circumvents the need to prefunctionalize both coupling partners for the generation of C–C bonds. Herein we report a cyclative C(sp3)–H/C(sp2)–H coupling reaction of free aliphatic acids enabled by a cyclopentane-based mono-N-protected β-amino acid ligand. This reaction uses inexpensive sodium percarbonate (Na2CO3·1.5H2O2) as the sole oxidant and generates water as the only byproduct. A range of biologically important scaffolds, including tetralins, chromanes, and indanes, can be easily prepared by this protocol. Finally, the synthetic application of this methodology is demonstrated by the concise total synthesis of (±)-russujaponol F in a four-step sequence starting from readily available phenylacetic acid and pivalic acid through sequential functionalizations of four C–H bonds.