Latest ArticlesAn efficient method was developed for the conjugate addition of water to various α, β-unsaturated ketones by using bismuth(Ⅲ) chloride as a catalyst. The reactions proceeded smoothly in the presence of a catalytic amount of BiCl3 (20 mol%) in aqueous media to furnish a variety of synthetically useful β-hydroxyl ketones in moderate to good yields. Apart from water molecule, various alcohols could also be employed as nucleophiles to react with α, β-unsaturated ketones, leading to β-alkoxyl ketones in modest to high yields. In addition, the mild reaction conditions also entailed the conjugate addition reactions to proceed with the tolerance to a range of functional groups.
This study presents a facile strategy for the formation of highly substituted butterfly 1, 4-adducts/9, 10-adducts via the Diels-Alder reaction of benzyne intermediates. The method achieves very good to excellent yields of the respective anthracene derivatives under mild conditions. This practical protocol is compatible with a variety of sensitive functional groups and provides access to difunctionalized bridge 1, 4-adducts/9, 10-adducts.
HYL derived from the venom of the solitary bee Hylaeus signatus (Hymenoptera:Colletidae) is an α-helical antimicrobial peptide with 16 residues. To explore whether HYL can be applied in anti-tumor therapy, we synthesized HYL and further modified its structure by using a solid-phase synthesis method, and then evaluated their antitumor activities. Firstly, we identified the key residues of HYL by alanine scanning strategy, and then a series of stapled peptides were synthesized by hydrocarbon stapling strategy without destroying the key residues. All the stapled peptides of HYL showed significant improvement not only in α-helicity, but also in antitumor activity and protease resistance when compared to the parent peptide HYL. The results showed that hydrophobicity and amphiphilicity are important factors affecting the antitumor activity of HYL, and the stapling strategy can significantly affect the proteolytic stability and helicity of HYL. What's more, we find that the stapled peptides HYL-14, HYL-16 and HYL-18 show a promising prospect for novel anti-tumor drug development.
A Sc(OTf)3-catalyzed [3 + 3] cycloaddition of 2, 2'-diester aziridines with β-(indol-2-yl)-α, β-unsaturated ketones was developed, affording polysubstituted tetrahydro-γ-carbolines in single diastereoisomers in good to excellent yields.
The H3 bivalent modifications of trimethylation at Lys9 and acetylation at Lys18 (H3-K9Me3-K18Ac) were identified to collectively recruit TRIM33 in the nodal signaling pathway. To understand the underlying mechanism of TRIM33 recruitment, the nucleosome core particles (NCPs) containing full-length H3-K9Me3-K18Ac were indispensable samples. Herein we developed a pseudo dipeptide strategy to efficiently prepare peptide segments, facilitating the chemical synthesis of H3-K9Me3-K18Ac at a tens of milligram scale. The synthetic H3-K9Me3-K18Ac was then examined by CD spectroscopy, which demonstrated a prominent shift compared to recombinant H3. Finally, bivalently modified NCPs were assembled and verified by gel mobility shift assay with good homogeneity.
Highly active N, O-doped hierarchical porous carbons (NOCs) are fabricated through the in-situ polymerization and pyrolysis of o-tolidine and p-benzoquinone. As-prepared NOCs have a variety of faradaic-active species (N-6, N-5 and O-I), high ion-accessible platform (1799 m2 /g) and hierarchically micro-meso-macro porous architecture. Consequently, the resultant NOC electrode delivers an advantageous specific capacitance (311 F/g), with a pseudocapacitive contribution of 37% in a threeelectrode configuration, and an enhanced energy output of 18.0 Wh/kg@350 W/kg owing to the enlarged faradaic effect in an aqueous redox-active cell. Besides, a competitive energy density (74.9 Wh/kg) and high-potential durability (87.8%) are achieved in an ionic liquid (EMIMBF4)-assembled device. This study sheds light on a straightforward avenue to optimize the faradaic activity and nanoarchitecture for advanced supercapacitors.
A supramolecular dimer of doxorubicin (DOX) was constructed via ternary host-guest interactions between cucurbit[8]uril (CB[8]) and tryptophan modified DOX (DOX-Trp, connected with an acid-labile bond) and we demonstrate for the first time that a supramolecular dimer of DOX can be formed upon homo-dimerization by CB[8], which may act as a stimuli pH-responsive, supramolecular DOX dimer prodrug system. This supramolecular DOX dimer transported DOX efficiently and selectively to cancer cells, thereby exhibiting significantly minimized cytotoxicity against noncancerous cells while maintaining effective cytotoxicity against cancer cells. Under this strategy, many other anticancer drugs could be chemically modified and loaded as a dimeric "ammunition" into CB[8] as supramolecular dimer prodrug systems (or a "jet fighter") for improved cancer therapy.
Drug delivery systems (DDSs) are of paramount importance to deliver drugs at the intended targets, e.g., tumor cells or tissue by prolonging blood circulation and optimizing the pharmaceutical profiles. However, the therapeutic efficacy of DDSs is severely impaired by insufficient or non-specific drug release. Dynamic chemical bonds having stimuli-liable properties are therefore introduced into DDSs for regulating the drug release kinetics. This review summarizes the recent advances of dynamic covalent chemistry in the DDSs for improving cancer therapy. The review discusses the constitutions of the major classes of dynamic covalent bonds, and the respective applications in the tumor-targeted DDSs which are based on the different responsive mechanisms, including acid-activatable and reduction-activatable. Furthermore, the review also discusses combination strategies of dual dynamic covalent bonds which can response to the complex tumor microenvironment much more accurately, and then summarizes and analyzes the prospects for the application of dynamic covalent chemistry in DDSs.
(±)-Crataegusnorin A (1a/1b) and B (2a/2b), two pairs of rare 8, 9'-epoxy-type norlignan enantiomers featuring a γ-butyrolactone ring, were isolated from the fruit of Crataegus pinnatifida. Their structures were determined via extensive spectroscopic analyses. Gauge-independent atomic orbital (GIAO) NMR chemical shift calculations, combined with the advanced statistical method DP4+ were employed to establish the relative configurations of four compounds. Next, chiral separation was accomplished by chiral chromatographic column and the absolute configurations of the four compounds were unambiguously assigned by comparison between their experimental electronic circular dichroism curves with the quantum-mechanically calculated curves based on time-dependent density functional theory (TDDFT). All the isolates were evaluated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells. The results showed that two pairs of enantiomers 1a/1b and 2a/2b displayed diff; erent effect on neuroprotective activity. Among them, compound 2a displayed the most potent neuroprotective effect. Further flow cytometry analysis indicated that 2a could protect SH-SY5Y cells from oxidative damage through inhibiting cell apoptosis.
Bioorthogonal cleavage and ligation reactions together form one more integrated system about the repertoire of bioorthogonal chemistry, capacitating an array of thrilling new biological applications. The bond-cleavage type and position of biomolecular remain a great challenge, which determines the metabolic pathway of the targets in living systems. Herein we designed two linkages of methylene and carbonyl group attached the N-3 position of the 5-ethynyl-2'-deoxyuridine (EdU) base or the oxygen atom at deoxyribose 3' position to a photocaging group, which would be cleaved by irradiation with 365 nm ultraviolet light. EdU derivatives linked by methylene at the N-3 position had better photodecage efficiency and stability in the absence of light. This paper provides a strategy for studying the nucleoside metabolic pathways in cells, which can easily and conveniently evaluate the effect of the position and type of the linkages. The developed strategy affords a reference for controlling spatial and temporal metabolism of small-molecule drugs, allowing direct manipulation of intact cells under physiological conditions.
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