Organic & Biomolecular Chemistry最新文献

We integrate a recyclable Rh-MOF heterogeneous catalyst into carbene-mediated three-component reactions of diazo compounds, alcohols and electrophiles. This system exhibits broad functional group tolerance, excellent diastereoselectivity, and high turnover number (TON = 856), while enabling continuous-flow gram-scale synthesis with prolonged operational stability.

A family of α-aminophosphonates, dimethyl (A), dipropyl (B), and diisopropyl (C), was synthesized through a green, catalyst-free Kabachnik-Fields reaction and characterized using FT-IR, NMR, and UV-Vis spectroscopy, single-crystal X-ray diffraction, DFT calculations, and multiscale physicochemical analyses. All compounds crystallize as asymmetric Janus-type dimers stabilized by strong intermolecular N-H⋯OP hydrogen bonds, with alkyl substituents tuning their packing efficiency, directional interactions, and supramolecular organization. SC-XRD and ωB97X-D calculations show excellent agreement with their bond lengths, angles, and overall geometry, validating their dimeric structural model. Vibrational and NMR data corroborate the donor-acceptor polarity of the amide N-H and phosphoryl groups, while XRPD and DLS measurements confirm their structural robustness and concentration-dependent aggregation. Photophysical analyses reveal consistent π → π* transitions on the aromatic amide core with substituent-dependent relaxation. Thermal analysis shows that A possesses the most ordered hydrogen-bonded lattice yet decomposes first due to internal strain, B melts earlier but decomposes slightly later owing to its reduced packing efficiency, and C exhibits the highest melting point via compact dispersive stabilization. DFT and QSAR results further indicate distinct electronic behaviors, where compound A exhibits stronger hydrogen-bonding propensity toward biological targets, B shows steric stabilization, and C balances polarity and hydrophobicity to achieve the most favorable drug-like profile. Overall, this study demonstrates that substituent-driven modulation of hydrogen bonding, steric effects, and dispersive forces enables precise control over the supramolecular and physicochemical properties of α-aminophosphonate dimers, positioning them as versatile scaffolds for pharmaceutical and materials applications.

Correction for 'Visible light photocatalytic reductive hydroalkylation and deuterium alkylation to access α-silylated bicyclo[1.1.1]pentanes' by Changlong Zheng et al., Org. Biomol. Chem., 2025, 23, 10458-10462, https://doi.org/10.1039/D5OB01555C.

For the first time, a four-center three-component Ugi reaction has been developed involving isonitriles, amines and bifunctional pyridine derivatives containing carbonyl and carboxyl groups (U-4C-3CR-Py). A series of fourteen new 1-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-3-carboxamides was synthesized using the proposed methodology. It was established that the reaction proceeds through the formation of an intermediate 3-(arylamino)furopyridinone, which was successfully isolated and reacted with an isonitrile to form the target products. The developed method is characterized by mild conditions, the absence of a catalyst and broad substrate scope with respect to both the amine and isonitrile components.

Four N,N-disubstituted pseudocyclic-type iodine(III) reagents were conveniently prepared in excellent yields from ortho-iodobenzamides using mCPBA as the oxidant under mild conditions. This class of hypervalent iodine(III) oxidants exhibited remarkable selectivity in oxidizing sulfides solely to sulfoxides, without any detectable sulfone formation, even when used in excess or at elevated temperatures. Mechanistically, the nucleophilic attack of sulfide generates the sulfonium intermediate, which enables the oxidation of sulfides.

In the search for β-galactofuranosidase inhibitors, the synthesis of 4-thio-D-galactonic acid 1,4-thiolactone and 4-deoxy-D-galactono-1,4-lactam was undertaken. These compounds are analogs of D-galactono-1,4-lactone, a known inhibitor of the enzyme. Additionally, a synthetic route to access benzyl, alkyl and hydroxyalkyl N-substituted galactonolactams is outlined. All syntheses began with derivatives of D-glucono-1,5- or 1,4-lactones as starting compounds. They underwent substitution at C-4 via sulfur or nitrogen nucleophiles, yielding products with galacto configuration. All synthesized compounds were found to inhibit the Penicillium fellutanum β-galactofuranosidase. 4-Thio-D-galactonic acid 1,4-thiolactone was a weak inhibitor, while 4-deoxy-D-galactono-1,4-lactam was the strongest (K_i = 88 ± 4 µM) within this series. Kinetic studies further revealed that this is a competitive inhibitor. Furthermore, a preliminary docking analysis with the β-galactofuranosidase from Streptomyces sp. JHA19 ORF 1110 demonstrated that the lactam is also a potential inhibitor of this enzyme. Inhibition of β-galactofuranosidases may serve as a novel chemotherapeutic approach for treating human pathogens that contain galactofuranosyl structures, such as those responsible for leprosy and tuberculosis.

Direct C-H functionalization on heteroaromatic rings has emerged as a prominent topic in the field of catalytic organic synthesis. Among these, oxidative coupling methodologies involving C-H bond functionalization have gained significant attention due to their step economy and energy efficiency. This synopsis focuses on recent advances in coupling reactions on various heteroaromatic rings via C-H bond functionalization. We made significant contributions to C-H functionalization on heteroaromatic rings and aim to provide a conceptual summary that will be useful to researchers and inspire further developments in this rapidly growing field.

A novel protocol of photodriven, TFA-mediated oxidative coupling of quinoxalin-2(1H)-ones with 5-pyrazolones to prepare 4-quinoxalinone-pyrazolones has been realized under air. A visible-light-catalyzed method was first employed to synthesize these derivatives and the reactions afforded the desired products moderate to excellent yields. This protocol can be applied to the efficient synthesis of quinoxalinone drug analogs. Mechanistic investigation suggested that a radical pathway exists and TFA plays an important role in the formation of the products.

Heparan sulfate (HS) analogs are synthetic oligo- and polysaccharides designed to mimic or enhance several biological properties of native HS. Organic synthesized compounds are very useful tools for understanding the structure-activity relationships of many biological events. Unlike heterogeneous mixtures of tissue-isolated biomolecules, synthetic compounds offer a valuable platform to probe structure-activity relationships with reduced off-target effects in pharmacological applications. In our research group, we are particularly focused on the design and synthesis of thiodisaccharide analogs mimicking HS structural motifs. In recently published work, we reported the synthesis and biological evaluation of both new sulfated and non-sulfated O- and S-linked disaccharides, demonstrating their potential as heparanase inhibitors. In this article, we introduced a sulfonate moiety as a stable analog of the sulfate group. Comparative heparanase inhibition assays reveal that sulfated disaccharides exhibit significantly greater activity than their sulfonated counterparts. Furthermore, multivalent glycoclusters were prepared by coupling sulfated thiodisaccharides to maltotriose and cyclodextrin scaffolds, providing novel molecular architectures that show promising heparanase inhibition.

A ruthenium-catalyzed one-pot sequential cascade has been developed for the synthesis of functionalized pyridazino[4,5-b]quinolin-1(2H)-ones. The sequence comprises Ru/Cu-catalyzed C(sp³)-H oxidation, cyclization with hydrazine hydrate, Chan-Lam N-H arylation, and Ru/Cu-mediated ortho-selective C(sp²)-H alkenylation in a single operation. Mechanistic studies highlight the crucial role of ruthenium in C-H activation and alkenylation. The N-aryl substitution of pyridazino[4,5-b]quinolin-1(2H)-one resulted in steric hindrance, which prevents free rotation around the C-N single bond (CN nature due to the amide, phenyl, and ortho bulky substituents), and hence showed inherent atropisomerism, as revealed by specific optical rotation (SOR) studies. Furthermore, the alkenylation at the o-position enhanced the restriction of free rotation and the atropisomeric products were obtained, as revealed by chiral HPLC analysis and SOR studies. However, further detailed chiral synthetic studies are required to understand the enantioselective versions, which are in progress in our laboratory and will be communicated separately. SC-XRD studies revealed that the crystallization of products occurs in centrosymmetric space groups. This efficient cascade offers a concise route to structurally diverse atropisomeric and functionalized pyridazinoquinolinones.