Chinese Journal of Chemistry最新文献

Six new acorane-type sesquiterpenes, named penijanacoranes A—F (1—6), as well as one known eudesmane sesquiterpenoid 1α,6β,11-eudesm-triol (7) have been isolated from a deep-sea-derived fungus Penicillium janthinellum SH0301. Their structures and absolute configurations were established by the comprehensive spectroscopic analysis, TDDFT-ECD calculations, and X-ray diffraction. Penijanacorane A (1) was identified as a rare acorane-type sesquiterpene lactone featuring a novel 6/5/6 tricyclic system, while penijanacoranes E and F (5 and 6) represented undescribed examples of nor-acorane sesquiterpenes at C-1. Penijanacorane C (3) exhibited significant inhibitory activity against LPS-induced NO production in Raw264.7 macrophages with an IC₅₀ value of 6.23 μM, which was more potent than that of positive control dexamethasone (IC₅₀ = 11.49 μM). This study expanded the chemical diversity of acorane-type sesquiterpenoids and revealed that compound 3 was a potential molecule for anti-inflammatory agents.

A tandem Diels–Alder reaction/Claisen rearrangement/decarboxylation strategy of N-allenamides (or aryloxyallenes) with 3-alkoxycarbonyl-2-pyrones has been developed for the efficient synthesis of diarylmethanes with moderate to good yields. The reaction exhibits good functional group tolerance and can be applied to late-stage modifications of known drug molecules. Mechanistic studies indicate that the ester group at the 3-position of 2-pyrones is essential, and the initial Diels–Alder reaction between the 2-pyrones and the proximal C=C bond of the N-allenamides (or aryloxyallenes) is crucial for the success of the reaction.

Conjugate addition and allylic substitution are two essential chemical transformations, and they could be competitive for substrates with multiple reactive sites. Herein, we report the diversified enantioselective synthesis of cyclobutenes via the functionalization of cyclobutenones. The conjugate addition of cyclobutenones with arylzinc halides provided enantioenriched cyclobutenes with all-carbon quaternary centers. On the other hand, when cyclobutenones with gem-dichloro groups were employed, a chemo- and enantioselective allylic substitution occurred. Further synthetic utility was demonstrated for synthesizing versatile cyclobutane derivatives, together with ring-opening and expansion products.

We report the design and development of a β-glucuronidase (β-Glu)-responsive ManNAz derivative, Glu-AAM, for tumor-selective metabolic glycoengineering. Glu-AAM enables specific labeling of tumor cell surface sialoglycans in the presence of overexpressed β-Glu in cancer cells, including breast, leukemia, and colorectal cancer cells. We demonstrate the high selectivity and efficiency of Glu-AAM-mediated metabolic glycoengineering across multiple cancer cell lines. Furthermore, we synthesized multivalent antibody-recruiting molecules (DBCO-Rha) that can be covalently attached to the azido-modified tumor cell surface, leading to potent antibody-dependent cellular phagocytosis and complement-dependent cytotoxicity. The octameric DBCO-Rha8 construct exhibited the most effective immune response. This integrated strategy of β-Glu-responsive metabolic glycoengineering and antibody-recruiting immunotherapy provides a promising platform for targeted cancer therapies and expands the toolbox of metabolic glycoengineering for cancer immunotherapy.

Photodynamic therapy (PDT) has been attracted a surge of research interest. However, there are several obstacles to limit the efficacy of PDT, such as hypoxic tumor microenvironment (TME), overexpressed glutathione (GSH), inefficient reactive oxygen species (ROS) generation, and so on. Herein, a smart responsive nanosystem was constructed, which was composed of Au₂₅ modified with triphenylphosphine (Au₂₅-TPP), catalase (CAT) and GSH-responsive diselenide-bridged mesoporous silica nanoparticles (Se-MSN). When the nanosystem arrived at tumor site, Se-MSN was degraded by the intracellular overexpressed GSH to release Au₂₅-TPP and CAT. The Au₂₅-TPP was targeted to mitochondria and generated ROS under the 808 nm NIR laser irradiation to kill tumor cells. Simultaneously, CAT could catalyze hydrogen peroxide to provide oxygen for relieving the hypoxia of TME. Besides, GSH was consumed by the diselenide bond to diminish the ROS loss. The above tactics (mitochondria targeting, hypoxia relieving and GSH consuming) jointly enhanced the PDT efficacy. The nanosystem showed distinct in vitro anticancer effect significantly stronger than other groups containing one or two assistance. Moreover, the in vivo results suggested that the tumors could be restrained obviously. The current study provides a new inspiration for constructing novel inorganic nanomedicines with multiple enhancement effect of PDT efficacy.

Traditional protecting groups are often removed under harsh conditions with potentially hazardous reagents, thereby impeding the convenient synthesis of oligosaccharides and glycosides. Herein, we present to utilize the photolabile ortho-nitro-benzyl carbonate (oNBC) as a permanent hydroxyl protecting group for stereocontrolled synthesis of glycosides. The Ph₃PO-modulated glycosylation with strongly disarmed per-O-oNBC-protected glycosyl ynenoates preferred to afford glycosides with excellent α-selectivities via the β-phosphonium transition state. Based on the oNBC-mediated galactosylation, synthesis of the glycolipid digalactosyl diacylglycerol (DGDG) containing six double bonds and two esters was achieved in a straightforward manner.

The pursuit of sustainable and environmentally benign synthetic methods continues to challenge organic chemists. Herein, we introduce a magnetoredox system for tri- and difluoromethylation of isocyanides and N-arylacrylamides using a rotating magnetic field and steel rods. This magnetoredox approach enables facile synthesis of functionalized phenanthridines and oxindoles without the need for catalysts and additives under mild conditions. Such a system potentially represents an attractive strategy for selective formation of bonds through multifaceted regulation of magnetic intensity, rotating frequency, and rod size.

Two families of cyclopentadienyl (Cp)/carboranyl heteroleptic sandwiched organolanthanide complexes, namely [Ln{η⁵:σ-Me₂C(C₅H₄)(C₂B₁₀H₁₀)}₂][Li(DME)₃] (1Ln, Ln = Tb, Dy, Ho, Er) and [2-THF-2'-(μ²-Cl)Li(THF)₃-2,2'-Ln(nido-1,7-C₂B₉H₁₁)Cp*] (2Dy), were synthesized. Family of 1Ln has been proposed based on the mixing-ligands idea by linking Cp and nido-dicarborllide. However, the carborane cage of [Me₂C(C₅H₄)(C₂B₁₀H₁₀)]²⁻ deprotons and forms a mono-C⁻ anion rather than deboron to form dicarborllide dianion. Hence, the family of 1Ln features a dysprosocenium skeleton with extra two coordination of C⁻ anions of carborllides. Such coordination geometry is more like a tetrahedron if abstracting the centroids of two coordinated Cp rings. In this cubic-type geometry, no significant magnetic axiality is presented; only 1Dy and 1Tb show field-induced slow magnetic relaxation behavior below 10 K. Inspired by 1Ln, the free pentamethylcyclopentadienyl (Cp*⁻) and nido-dicarborllide ligands are used to sandwich central Dy³⁺ ion, achieving heteroleptic complex 2Dy. The bending angle by linking the centroid of Cp*⁻, Dy³⁺ and C₂B₃²⁻ in 2Dy is increased to 132.8(1)°. As such, the effective energy barrier for magnetic reversal (U_eff) and magnetic blocking temperature T_B (ZFC) are both increased (U_eff = 616(10) K; T_B = 6 K). The effort of further enhancing U_eff and T_B in such heteroleptic organolanthanide sandwiches should rely on keeping increasing the ligand axiality.

Oil-in-oil nonaqueous emulsions are of great interest for developing emulsion-templated polymers and encapsulation systems that are incompatible with water-sensitive substances. Tailor-made amphiphilic block copolymers are by far the most efficient stabilizers for oil-in-oil emulsions while less attention is given to copolymers with more complex architectures. Here, we report the stabilization of DMSO-silicone oil interface by bottlebrush random copolymers (BRCPs) containing norbornene backbones with densely grafted poly(methyl methacrylate) (PMMA) and polystyrene (PS) side chains. The assembly kinetics of BRCPs at the DMSO-silicone oil interface can be divided into three processes, including diffusion, reconfiguration and reorganization, and can be varied by tuning the degree of polymerization of the backbone (N_B). Due to the high efficiency of BRCPs in reducing the interfacial tension, when using BRCPs as stabilizers, stable silicone oil-in-DMSO traditional emulsions and high internal phase emulsions (HIPEs) can be successfully obtained, while no stable emulsions can be achieved with linear PMMA-b-PS serving as the stabilizer. This study, for the first time, underscores the great potential of amphiphilic bottlebrush copolymers in preparing oil-in-oil emulsions. Given the advances in polymerization strategy, a broad variety of amphiphilic bottlebrush copolymers are expected to be synthesized and applied in the stabilization of nonaqueous biphasic systems.