Despite the potential of chiral peroxides as biologically interesting or even clinically important compounds, no catalytic enantioselective peroxidation has been reported. With a chiral catalyst not ...only to induce enantioselectivity but also to convert a well established epoxidation pathway into a peroxidation pathway, the first efficient catalytic peroxidation has been successfully developed. Employing readily available α,β-unsaturated ketones and hydroperoxides and an easily accessible cinchona alkaloid catalyst, this novel reaction will open new possibilities in the asymmetric synthesis of chiral peroxides. Under different conditions a highly enantioselective epoxidation with the same starting materials, reagents, and catalyst has was also established.
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The clinical success of cancer nanomedicines critically depends on availability of simple, safe and highly efficient nanocarriers. Here, we report that robust and multifunctional ...nanoparticles self-assembled from hyaluronic acid-g-poly(γ-benzyl-l-glutamate)-lipoic acid conjugates achieve a remarkably high loading (up to 25.8wt.%) and active targeted delivery of doxorubicin (DOX) to human breast tumor xenograft in vivo. DOX-loaded nanoparticles following auto-crosslinking (DOX-CLNPs) are highly stable with little drug leakage under physiological conditions while quickly release ca. 92% DOX in 30h under a cytoplasmic-mimicking reductive environment. The in vitro assays reveal that DOX-CLNPs possess a superior selectivity and antitumor activity to clinically used pegylated liposomal doxorubicin hydrochloride (DOX-LPs) in CD44 receptor overexpressing MCF-7 human breast cancer cells. Strikingly, DOX-CLNPs exhibit a superb tolerated dose of over 100mg DOX equiv./kg, which is more than 5 times higher than DOX-LPs, and an extraordinary breast tumor accumulation of 8.6%ID/g in mice. The in vivo therapeutic studies in MCF-7 human breast tumor-bearing nude mice show that DOX-CLNPs effectively inhibit tumor growth, improve survival rate, and significantly decrease adverse effects as compared to DOX-LPs. DOX-CLNPs based on natural endogenous materials with high drug loading, great stability and CD44-targetability are highly promising for precision cancer chemotherapy.
We demonstrate that with rational design, simple and multifunctional anticancer nanotherapeutics can be developed to achieve highly efficient and targeted cancer chemotherapy. Doxorubicin-loaded multifunctional nanoparticles based on hyaluronic acid-g-poly(γ-benzyl-l-glutamate)-lipoic acid conjugates exhibit a high drug loading, superior stability, fast bioresponsivity, high tolerability, and obvious selectivity toward CD44-overexpressing tumors in vivo. These nanotherapeutics achieve effective tumor suppression, drastically improved survival rate and reduced side effects as compared to clinically used pegylated liposomal doxorubicin in MCF-7 human breast tumor-bearing nude mice. Unlike previously reported multifunctional nanomedicines, the present nanotherapeutics primarily based on natural endogenous materials are simple and straightforward to fabricate, which makes them potentially interesting for clinical translation.
In this communication, we describe an unprecedented highly enantioselective catalytic conjugate addition of simple alkyl thiols to α,β-unsaturated N-acylated oxazolidin-2-ones catalyzed by acid−base ...bifunctional catalysis. This reaction provides a useful catalytic method for the synthesis of optically active chiral sulfur compounds that are otherwise difficult to prepare by asymmetric catalysis. The successful development of this reaction resulted from a discovery that, upon proper modification, a cinchona alkaloid bearing a thiourea functionality at 6′ position can afford highly efficient catalysis for asymmetric conjugate additions.
Δ2‐Pyrazolines are of significant medicinal and synthetic interest due to their therapeutic properties and utility in the synthesis of 1,3‐diamines, yet few asymmetric methods exist to prepare them. ...An unprecedented and highly enantioselective organocatalytic synthesis of 2‐pyrazolines was achieved through an asymmetric conjugate addition catalyzed by 9‐epi‐amino Cinchona alkaloids followed by deprotection‐cyclization, which furnished chiral 2‐pyrazolines in 46–78% yield and 59–91% ee. This bifunctional catalytic methodology thus provides easy access to a considerable range of optically active 3,5‐dialkyl 2‐pyrazolines.
The novel synthetic strategy for dolabellane skeleton was realized, which allowed the synthesis of clavulactone analogues 26 and 27 in a concise and efficient manner. Salient transformations include ...a diastereoselective Mukaiyama aldol reaction, an intramolecular nucleophilic addition reaction, a Grob fragmentation reaction, and an efficient Mukaiyama–Michael addition reaction.
In our synthetic studies toward huperzine A, a diastereoselective α′-alkylation of the α-amido-γ-methyl hexenone
4
was realized through a dianion intermediate which significantly enhanced the ...reactivity. Under the attempted Heck reaction conditions, an unexpected and unprecedented palladium-catalyzed intramolecular γ-arylation of
3
was observed, which generated
18
with bicyclo3.3.1nonane framework in satisfactory yield.
Abstract This paper continued our earlier work on the poly( d , l -lactide- co -glycolide)/montmorillonite nanoparticles (PLGA/MMT NPs), which were further decorated by human epidermal growth factor ...receptor-2 (HER2) antibody Trastuzumab for targeted breast cancer chemotherapy with paclitaxel as a model anticancer drug. Such a NP system is multifunctional, which formulates anticancer drugs with no harmful adjuvant, reduces the side effects of the formulated anticancer drug, promotes synergistic therapeutic effects, and achieves targeted delivery of the therapy. The paclitaxel-loaded PLGA/MMT NPs were prepared by a modified solvent extraction/evaporation technique, which were then decorated with Trastuzumab. The effects of the surface decoration on particle size and size distribution, surface morphology, drug encapsulation efficiency, as well as the drug release kinetics, were investigated. The NP formulation exhibited a biphasic drug release with a moderate initial burst followed by a sustained release profile. The surface decoration speeded the drug release. Surface chemistry analysis was conducted by X-ray photoelectron spectroscopy (XPS), which confirmed the presence of Trastuzumab on the NP surface. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed the stability of the antibody in the NP preparation process. Internalization of the coumarin-6-loaded PLGA/MMT NPs with or without the antibody decoration by both of Caco-2 colon adeno carcinoma cells and SK-BR-3 breast cancer cells was visualized by confocal laser scanning microscopy and quantitatively analyzed, which shows that the antibody decoration achieved significantly higher cellular uptake of the NPs. The results of in vitro cytotoxicity experiment on SK-BR-3 cells further proved the targeting effects of the antibody decoration. Judged by IC50 after 24 h culture, the therapeutic effects of the drug formulated in the NPs with surface decoration could be 12.74 times higher than that of the bare NPs and 13.11 times higher than Taxol®.
This paper proposes a new approach for investigating the mechanism of the formation of the active phase of a hydrodesulfurization (HDS) catalyst via crystalline polyoxometalate (POM) precursors. The ...proposed strategy induces the crystallization of small Ni–Mo–O clusters in an impregnating solution by the coordinate bonding and supramolecular interaction of organic ligands to form POMs. By exploiting the “ligand-induced self-assembly” strategy, two Ni–Mo binary POMs with different frameworks, namely, Mo 2 Ni and PMo 11 Ni, were isolated from the impregnating solution by means of 4,4′-bpy. The sulfidation process of the precursors and the formation mechanism of the NiMoS active phase were fully characterized by a multi-technique approach that comprised, in particular, in situ FT-IR spectroscopy, XRD and Raman spectroscopy for different degrees of sulfidation. The results of the characterization revealed the structure-directing effects (framework effect, promoting effect and ligand effect) of the POM precursors on the structure of the active phase and even its HDS performance. MoS 2 was formed at 200 °C from Mo 2 Ni, and the Ni species interacted with the edges of MoS 2 to form the NiMoS active phase, whereas PMo 11 Ni formed MoS 2 at 300 °C. The structure-directing effects enabled a higher content and better dispersion of the NiMoS active phase, which explains the higher HDS reactivity of sulfided Mo 2 Ni. The bottom-up self-assembly approach not only provides a better understanding of the composition of the impregnating solution and the formation mechanism of the NiMoS active phase but also sheds light on the rational design and controllable preparation of NiMoS catalysts with high performance.
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