Qingfeng Liu

Synthesis of [60]fullerene-fused tetrahydroazepinones and azepinonimines via Cu(OAc)2-promoted N-heteroannulation reaction.

A convenient and efficient Cu(OAc)2-mediated N-heteroannulation reaction of [60]fullerene with N-sulfonylated o-amino-aromatic methyl ketones or O-alkyl oximes has been reported for the synthesis of novel and scarce [60]fullerene-fused tetrahydroazepinones and -azepinonimines in a highly selective manner. Moreover, a possible mechanism involving two pathways is proposed on the basis of the experimental observations.

In vitro and in vivo study of thymosin alpha1 biodegradable in situ forming poly(lactide-co-glycolide) implants

The purpose of this study was to develop poly(lactide-co-glycolide) (PLGA) based in situ forming implants (ISFI) for controlled release of thymosin alpha 1 (Talpha1). The ISFI was prepared by dissolving PLGA in N-methyl-2-pyrrolidone (NMP) or mixtures of NMP and triacetin. Talpha1 microparticles, prepared by spray-freeze drying method with chitosan or bovine serum albumin as a protectant, were suspended in PLGA solutions. The effects of Talpha1 pre-encapsulation, PLGA molecular weight, PLGA concentration and organic solvents composition on the in vivo Talpha1 release were evaluated by subcutaneously injecting Talpha1-loaded ISFI into Sprague-Dawley Rats. The pharmacological efficacy of Talpha1-loaded ISFI was examined using immunosuppressive BALB/c mice induced by cyclophosphamide. The ISFI composed of Talpha1 pre-encapsulated with chitosan, higher molecule-weight PLGA at higher concentration and more triacetin showed a lower initial release and a longer sustained release period. The optimal prescription of our study showed a low initial release of 29.3% (24 h), followed by a slow and continuous drug release up to 28 d in vivo. An in vitro release device was designed to mimic the in vivo release of Talpha1, and good correlation was observed between the in vitro and in vivo releases, with the linear correlation coefficient of 0.9899. Talpha1-loaded ISFI showed low cytotoxicity as tested by CCK-8 assay. Talpha1-loaded ISFI significantly increased the thymic index and spleen index of immunosuppressive mice. These results suggest that the ISFI is a suitable system for controlled release of Talpha1.

Dimethyl sulfoxide participant iron-mediated cascade oxidation/α-formylation reaction of substituted 2,3-dihydropyrroles under air and protonic acid free condition.

An efficient and Brønsted acid free one-pot protocol to directly generate structurally sophisticated α-formylpyrrole derivatives in moderate to good yields has been demonstrated, involving an iron-mediated domino oxidation/formylation reaction of readily available 2,3-dihydro-1H-pyrroles in dimethyl sulfoxide and air atmosphere, in which dimethyl sulfoxide acts as the formyl donor. A possible mechanism is presented.

Study on the Interaction of an Anthracycline Disaccharide with DNA by Spectroscopic Techniques and Molecular Modeling

This study was designed to examine the interaction of 4′-O-(a-L-Cladinosyl) daunorubicin (DNR–D5), a disaccharide anthracycline with calf thymus deoxyribonucleic acid (ctDNA) by UV/Vis in combination with fluorescence spectroscopy and molecular modeling techniques under physiological conditions (Britton–Robinson buffer solutions, pH = 7.4). By the analysis of UV/Vis spectrum, it was observed that upon binding to ctDNA the anthraquinone chromophore of DNR–D5 could slide into the base pairs. Moreover, the large binding constant indicated DNR–D5 had a high affinity with ctDNA. At the same time, fluorescence spectra suggested that the quenching mechanism of the interaction of DNR–D5 to ctDNA was a static quenching type. The binding constants between DNR–D5 and ctDNA were calculated based on fluorescence quenching data at different temperatures. The negative ∆G implied that the binding process was spontaneous, and negative ∆H and negative ΔS suggested that hydrogen bonding force most likely played a major role in the binding of DNR–D5 to ctDNA. Moreover, the results obtained from molecular docking corroborate the experimental results obtained from spectroscopic investigations.

Selective reduction of aldehydes and ketones to alcohols with ammonia borane in neat water

Chemoselective reduction of various carbonyl compounds to alcohols with ammonia borane (AB), a nontoxic, environmentally benign, and easily handled reagent, in neat water was achieved in quantitative conversions and high isolated yields. Interestingly, α- and β-keto esters were selectively reduced to corresponding hydroxyl esters by AB, while diols were obtained when sodium borohydride was used as a reducing agent. The procedure is also compatible with the presence of a variety of base-labile protecting groups, such as tosyl, acetyl, benzoyl, ester groups, and acid-labile protecting groups such as trityl and TBDMS groups, and others, such as the unsaturated double bond, nitro and cyano groups. Finally, a kilo scale reaction of methyl benzoylformate with AB was conducted in water and gave methyl mandelate in 94% yield.

Approach to Polysubstituted 4-Pyridones from N-Aryl Acetoacetamides via a N to C 1,3-Acyl Migration Mediated by Sodium Persulfate

Mediated by sodium persulfate (Na(2)S(2)O(8)), a series of polysubstituted 4-pyridones were synthesized via self-condensation of N-aryl acetoacetamides, during which a novel N to C 1,3-acyl migration should be involved. The structure of 4-pyridone was unequivocally confirmed by X-ray diffraction analysis. However, the self-condensation of N-benzyl acetoacetamides under the same condition gave polysubstituted 2-pyridones instead of 4-pyridones.

Synthesis of multisubstituted pyrroles from doubly activated cyclopropanes using an iron-mediated oxidation domino reaction.

An alternative route has been developed for the construction of multisubstituted pyrrole derivatives from readily available, doubly activated cyclopropanes and anilines using an iron-mediated oxidation domino reaction (i.e., sequential ring-opening, cyclization, and dehydrogenation reactions). This reaction uses readily available reactants and is tolerant of a broad range of substrates, with the desired products being formed in good to excellent yields.

Iron-catalyzed vinylogous aldol condensation of Biginelli products and its application toward pyrido[4,3-d]pyrimidinones.

A novel iron-catalyzed vinylogous aldol condensation of Biginelli products with aryl aldehydes has been developed for the syntheses of potential bioactive (E)-6-arylvinyl-dihydropyrimidin-2(1H)-ones. These materials are valuable synthetic precursors to drug-like pyrido[4,3-d]pyrimidine derivatives. The amide group at the 5-position of the dihydropyrimidin-2(1H)-ones played an important role in the vinylogous aldol condensation reaction.

Iron-Catalyzed Intramolecular C(sp(2))-N Cyclization of 1-(N-Arylpyrrol-2-yl)ethanone O-Acetyl Oximes toward Pyrrolo[1,2-a]quinoxaline Derivatives

An efficient and convenient iron-catalyzed protocol has been developed for the synthesis of substituted pyrrolo[1,2-a]quinoxalines from 1-(N-arylpyrrol-2-yl)ethanone O-acetyl oximes through N-O bond cleavage and intramolecular directed C-H arylation reactions in acetic acid.

Catalyst-free and highly selective electrophilic mono-fluorination of acetoacetamides: facile and efficient preparation of 2-fluoroacetoacetamides in PEG-400

Series of α-mono-fluorinated acetoacetamides were synthesized under mild condition with industrialized Selectfluor as the F+ source in PEG-400. The approach avoided the use of base or metal catalyst, and most of cases proceeded in nearly quantitative conversions regardless of the electronic nature of the diversity substituent.