Development and validation of a QuEChERS-HPLC-DAD method using polymer-functionalized melamine sponges for the analysis of antipsychotic drugs in milk.

The prohibition of antipsychotic drugs in animal foodstuffs has raised significant concerns. In this study, a novel matrix purification adsorbent comprising a polymer (polyaniline and polypyrrole)-functionalized melamine sponge (Ms) was employed for the high performance liquid chromatography-diode array detector (HPLC-DAD) detection of three phenothiazines (chlorpromazine, thioridazine, and promethazine), and a tricyclic imipramine in milk. The as-prepared functionalized Ms was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and water contact angle measurements. Excellent linearity with a coefficient of determination (R2) of 0.999 was achieved for all drugs within the concentration range of 0.01-47.00 µg mL-1. The recoveries of the four analytes ranged from 92.1 % to 106.9 % at the three spiked levels. These results demonstrate the successful application of the proposed method for the determination of the four drugs. Cost-effective polymer-functionalized Ms is a viable alternative for matrix purification, enabling rapid determination of drug residues in diverse food samples.

Diversity-oriented and diastereoselective synthesis of diverse polycyclic thieno(2,3-b)-quinoline derivatives using a synergistic strategy.

A cascade spiroannulation of 2-mercaptoquinoline-3-carbaldehydes with α,α-dicyanoalkenes as well as a cascade spiroannulation of 2-mercaptoquinoline-3-carbaldehydes aldehydes with α-bromocarbonyl compounds was investigated based on a synergistic strategy, providing a series of diverse spiro-fused heterocyclic compounds containing more different functional groups. The features of this strategy directed towards molecular complexity and diversity include step economy, mild conditions, and high bond-forming efficiency, but important polycyclic heterocyclic products, which could be transformed into potential biologically interesting heterocyclic structures.

Umpolung Strategy for the Synthesis of Chiral Dispiro[2-amino-4,5-dihydrofuran-3-carbonitrile]bisoxindoles.

Based on a novel umpolung strategy, an efficient and highly enantioselective cascade aldol/cyclization/tautomerization of the 2-(2-oxoindolin-3-yl)malononitrile to active carbonyl compounds with excellent diastereo- and enantioselectivity has been developed. Also, various enantio-enriched multifunctional dispiro[2-amino-4,5-dihydrofuran-3-carbonitrile]bisoxindoles with adjacent spiro-stereocenters were conveniently obtained by this novel methodology. Also, the dispiro[2-amino-4,5-dihydrofuran-3-carbonitrile]bisoxindoles were easily transformed into structurally complex molecules without any effect on the diastereo- and enantioselectivity.

Chemoselective Synthesis of Structurally Diverse 3,4-Dihydroquinazoline-2(1H)-thiones and 4H-Benzo[d][1,3]thiazines.

An efficient, mild, and substrate/catalyst-controlled chemoselective reaction of o-isothiocyanato-(E)-cinnamaldehyde with amines has been established, producing three types of six-membered heterocycles: 2-(4H-benzo[d][1,3]thiazin-4-yl)acetaldehydes, 2-(2-thioxo-1,2,3,4-tetrahydroquinazolin-4-yl)acetaldehydes, and (E)-4-(2-methoxyvinyl)-4H-benzo[d][1,3]thiazines. The reaction scopes were quite broad and excellent yield was achieved. This method is extremely efficient and practical and can be conducted on a gram-scale with slightly inferior reactivity under catalyst-free conditions at low cost, making it an ideal alternative to existing methods.

A Simple and Versatile Method for the Formation of Acetals/Ketals Using Trace Conventional Acids.

An important and surprising finding that the acetalization and ketalization of aldehydes and ketones with alcohols, respectively, proceed smoothly in the presence of 0.1 mol % acid, without removing water, has been presented. This process has many merits, such as commercial available catalysts with low cost and low loadings (as low as 0.03 mol %), quite a broad substrate scope (including various aldehydes, ketones, acid-sensitive substrates, and diols), a wide range of reaction temperature (-60 to 50 °C), high yields, large-scale preparation, environmental friendliness, and simple work-up procedure. This new protocol has also been successfully applied to protect the important organic compounds, such as 1,3-diols, 1,2-diols, acid-sensitive substrates, glucose, and 1,3-dicarbonyl compounds.

Catalyst-Controlled Switch in Diastereoselectivities: Enantioselective Construction of Functionalized 3,4-Dihydro-2H-thiopyrano[2,3-b]quinolines with Three Contiguous Stereocenters.

A tandem Michael-Henry reaction of 2-mercaptoquinoline-3-carbaldehydes with nitroolefins using hydrogen-bonding-based cooperative organocatalysts for the highly diastereodivergent synthesis of chiral functionalized 3,4-dihydro-2H-thiopyrano[2,3-b]quinolines with three contiguous tertiary stereocenters has been developed.

Enantioselective Synthesis of Ring-Fused Spiroannulated 1,2,3-Thiadiazole Derivatives.

An organocatalytic enantioselective domino α-amination/oxidative coupling/cyclization of thioamides to azodicarboxylates catalyzed by an easily available organic catalyst has been developed. The key step, oxidative coupling, is smoothly fulfilled in air. Optically active spiroannulated 1,2,3-thiadiazole derivatives are obtained with high yields and enantioselectivities for the first time.

Tandem Copper-Catalyzed Propargylation/Alkyne Azacyclization/Isomerization Reaction under Microwave Irradiation: Synthesis of Fully Substituted Pyrroles.

A copper-catalyzed and microwave-assisted synthesis of fully substituted pyrroles has been developed. A series of pentasubstituted pyrroles, especially α-arylpyrroles, could be obtained in moderate to good yields (up to 93%) through a tandem propargylation/alkyne azacyclization/isomerization sequence from readily available ß-enamino compounds and propargyl acetates.

Synthesis of 2,3-Dihydrothieno(2,3-b)quinolines and Thieno(2,3-b)- quinolines via an Unexpected Domino Aza-MBH/Alkylation/Aldol Reaction.

An efficient, mild, and convenient method for the preparation of 2,3-dihydrothieno(2,3-b)quinolines and thieno(2,3-b)-quinolines via an unexpected domino aza-Morita-Baylis-Hillman/alkylation/aldol reaction has been developed. The plausible mechanisms for the unexpected reaction are also given.

Enantioselective Construction of Polyfunctionalized Spiroannulated Dihydrothiophenes via a Formal Thio [3+2] Cyclization.

A formal thio [3+2] cyclization catalyzed by Takemoto's organocatalyst has been reported for the construction of optically active spiroannulated dihydrothiophenes in high yields with excellent regio-, chemo-, diastereo-, and enantioselectivities.

Synthesis and antifungal activities of novel polyheterocyclic spirooxindole derivatives.

A series of spirooxindole tetrahydrofuran derivatives 3 were obtained in moderate to good yields via oxindole derivatives 1 and ß-arylacrylonitrile derivatives 2via base-mediated cascade [3 + 2] double Michael reactions under mild conditions and the application of this method in the synthesis of bioactive analogues, such as functionalized spirooxindole octahydrofuro[3,4-c]pyridine derivatives 4 which contain two new heterocyclic rings and two quaternary carbon centers, has also been developed. Subsequently, antifungal activities of all of the synthesized compounds were evaluated against five phytopathogenic fungi (Rhizoctonia solani, Fusarium semitectum, Alternaria solani, Valsa mali and Fusarium graminearum) using the mycelium growth rate method. The preliminary results showed that the spirooxindole octahydrofuro[3,4-c]pyridine derivative 4 showed higher growth inhibition of Valsa mali and Fusarium graminearum, than spirooxindole tetrahydrofuran derivatives 3. For example, spirooxindole octahydrofuro[3,4-c]pyridine derivative 4ab, having a bromine atom at the meta position of the benzene ring, was the best compound in inhibiting F. g. with an IC50 value of 3.31, in particular with inhibition of 4ab on F. g. being similar to that of the control cycloheximide (IC50 = 3.3 µg mL(-1)).

Asymmetric catalytic [4 + 1] annulations catalyzed by quinidine: enantioselective synthesis of multi-functionalized isoxazoline N-oxides.

A highly regio-, chemo-, diastereo- and enantioselective organocatalytic [4 + 1] annulation of 2-halo-1,3-dicarbonyl compounds with Morita-Baylis-Hillman adducts catalyzed by commercially available, low cost quinidine for the preparation of synthetically unique and medicinally multi-functionalized isoxazoline N-oxides with three stereogenic centers including adjacent quaternary and tertiary stereocenters has been developed. Notably, the unexpected product ethyl 2-((tert-butyldimethylsilyl)oxy)-2-(5,5-diacetyl-3-((methylsulfonyl)oxy)-4-phenylisoxazolidin-3-yl)acetate (8) bearing a quaternary stereocenter and two tertiary stereocenters was obtained from the undocumented 5,5-diacetyl-3-(2-ethoxy-1-hydroxy-2-oxoethyl)-4-phenyl-4,5-dihydroisoxazole 2-oxide (4ba).

Construction of functionalized 2,3-dihydro-1,4-benzoxazines via [5 + 1] annulations of 2-halo-1,3-dicarbonyl compounds with imines.

A series of functionalized 2,3-dihydro-1,4-benzoxazines were obtained in moderate to excellent yields via domino [5 + 1] annulations of 2-halo-1,3-dicarbonyl compounds 2 with imines 1 under mild conditions and the application of this method in the synthesis of bioactive analogues, such as functionalized tetracyclic-1,4-benzoxazines which contain two new heterocyclic rings and one quaternary carbon center has also been developed.

Synthesis of functionalized 2,3-dihydroisoxazoles by domino reactions in water and unexpected ring-opening reactions of 2,3-dihydroisoxazoles.

α,α-Dicyanoolefins react with hydroxylamine to afford 2,3-dihydroisoxazoles (2,3-dihydroisoxazoles can be easily isolated by filtration) in excellent yields under mild and environmentally benign conditions. A one-pot reaction in tandem with an unexpected ring-opening of 2,3-dihydroisoxazoles has been developed as well.

K2CO3-promoted domino reactions: construction of functionalized 2,3-dihydrobenzofurans and clofibrate analogues.

The K(2)CO(3)-catalyzed domino reactions (Michael alkylation, Mannich alkylation, and aldol alkylation) of salicylic aldehyde derivatives (2-hydroxyaryl-α,ß-unsaturated ketones, 2-hydroxyarylnitroalkenes, 2-hydroxyarylimines, and salicylic aldehydes) and 2-halo-1,3-dicarbonyl compounds (diethyl α-bromomalonate, diethyl α-chloromalonate, ethyl 2-chloroacetoacetate, and 3-chloropentane-2,4-dione) were carried out under mild conditions to provide a series of functionalized 2,3-dihydrobenzofurans in moderate to excellent yields. The novel transformations simultaneously gave a series of clofibrate analogues, which possess various substitution patterns.

Facile domino access to chiral mono-, bi-, and tricyclic 2,3-dihydrofurans.

The asymmetric domino Michael-S(N)2 reaction of various 1,3-dicarbonyl compounds to α-bromonitroalkenes is described for the first time, employing readily available cinchona-derived bifunctional thioureas as organocatalysts. The novel transformations were highly regio-, chemo-, diastereo-, and enantioselective, which simultaneously gave the chiral tricyclic 2,3-dihydrofurans, bicyclic 2,3-dihydrofurans, and tetrasubstituted 2,3-dihydrofurans with two vicinal chiral carbon centers.

The organocatalytic two-step synthesis of diversely functionalized tricyclic tetrazoles.

The diversely functionalized tricyclic tetrazoles were synthesised from readily available substrates via intramolecular 1,3-dipolar cycloaddition as the key step in good yields (53-78% yield for two steps) with high enantioselectivities (81-99% ee).

Efficient kinetic resolution of racemic 3-nitro-2H-chromene derivatives catalyzed by Takemoto's organocatalyst.

Efficient kinetic resolution of racemic 3-nitro-2H-chromenes by bifunctional thiourea afforded optically active (R)-3-nitro-2H-chromene derivatives with moderate to good enantioselectivities, which simultaneously gave the multifunctional 3,4-diphenyl-3a-nitrobenzopyrano-[3,4-c]-pyrrolidine-1,1-dicarboxylate derivatives with four vicinal chiral carbon centers.

Efficient method for the synthesis of functionalized pyrazoles by catalyst-free one-pot tandem reaction of nitroalkenes with ethyl diazoacetate.

The one-pot synthesis of multisubstituted pyrazole derivatives was achieved via catalyst-free 1,3-dipolar cycloaddition of ethyl diazoacetate and nitroalkenes as the key step and elimination of the leaving group (NO(2) or Br) followed by intramolecular proton transfer with satisfactory yields.

Stereoselective desymmetrisation of prochiral alpha,alpha-dicyanoalkenes via domino Michael-Michael addition reactions.

The desymmetrisation of prochiral alpha,alpha-dicyanoalkenes via tandem Michael-Michael addition reactions with alpha,beta-unsaturated ketones catalysed by 9-amino-9-deoxyepicinchona alkaloids was investigated, from which bicyclic products bearing four stereogenic centers were afforded in a single operation with high stereoselectivities (>99% de, up to >99.5% ee).