Vinylogous and stereoselective domino synthesis of pyrano[2,3-c]pyrroles from alkylidene meldrum's acids.

A domino Vinylogous aza-Michael-Aldol-Cyclocondensation (aza-VMAC) reaction was achieved with a series of alkylidene Meldrum's acid derivatives under simple operational conditions paving the way to novel pyrano[2,3-c]pyrroles in an excellent diasteroselectivity (>96 : 4), encompassing the relative control of three contiguous stereocenters.

An Organocatalytic and Stereoselective Vinylogous Domino Process towards Thiochromans.

A highly diastereoselective organocatalyzed domino vinylogous sulfa-Michael-aldol-cyclocondensation (VMAC) reaction has been developed using alkylidene Meldrum's acid as dienes highlighting two vinylogous steps, an unprecedented sulfa-1,6-conjugate addition and a diastereoselective aldol reaction triggering a formal (4+2) cycloaddition. This work opens a new route towards bio-relevant and original tricyclic thiochroman derivatives.

Vinblastine loaded on graphene quantum dots and its anticancer applications.

AIMS: The aim of our work is to load Vinblastine drugs loaded on graphene quantum dots to improve its cytotoxicity on cancer cells and reduce it on the normal cell in the composites. Moreover, the GQDs-Vin composite significantly inhibited tumour growth in animals. METHODS: GQDs-Vin composites were prepared by homogenisation of GQDs and Vin solutions. The loading of Vin on GQDs in the composites was characterised by FTIR, PL, UV-vis spectra, and TEM. The cytotoxicity of GQDs, Vin, and GQDs-Vin composites was investigated on the Hela, HGC-27, A549, MCF-7, CCF-STTG1 cells and Vero by in vitro and in vivo methods. The difference in cellular structure and organelles in mice's livers in comparison between the control group and GQDs-Vin (1:5) groups was characterised by TEM. RESULTS: The diameter of the nanoparticles of GQDs-Vin composites in weight ratios 1:1, 1:3 and 1:5 w/w of 50-70 nm, 100-150 nm and ∼500nm, respectively, is larger than that of GQDs of 10-50nm. The in vitro results showed that GQDs not only improved the cytotoxicity of Vin to cancer cells but also decreased its cytotoxicity towards normal cells in the composites. The GQDs-Vin (1:5) composite exhibited a stronger tumour inhibition effect than Vin alone. The morphology of mice's livers showed the absence GQDs-Vin nanoparticles in the mice livers suggesting the lack of storage and the leakage from the liver without any toxicity. CONCLUSIONS: Results of the improved cytotoxicity of GQDs-Vin composite on cancer cells, its reduced cytotoxicity on normal cells and the significant inhibition on tumour growth of GQDs-Vin composite compared with Vin and GQDs alone may indicate a synergistic effect of Vin and GQDs in their composites for anticancer application.

Enantioselective hydrophosphonylation of N-Boc imines using chiral guanidine-thiourea catalysts.

The enantioselective hydrophosphonylation of N-Boc imines was investigated using a new family of pseudo-symmetric guanidine-thiourea catalysts, providing α-amino phosphonates in moderate to high yields with good enantioselectivity. The catalyst was heterogenized by polymerization with styrene and the resulting catalyst was applied to reactions under continuous-flow conditions.

Alkylidene Meldrum's Acids as Platforms for the Vinylogous Synthesis of Dihydropyranones.

Upon Brønsted base organocatalysis, ketone-derived alkylidene Meldrum's acids proved to be competent vinylogous platforms able to undergo a formal (4+2) cycloaddition reaction with dihydro-2,3-furandione, providing an unprecedented route to 3,6-dihydropyran-2-ones as spiro[4.5]decane derivatives with up to 98 % ee thanks to the commercially available Takemoto catalyst. Preliminary investigation showed that this reaction could be extended to other activated ketones, establishing these alkylidene Meldrum's acids as a novel C4-synthon in the vinylogous series.

Divergent Synthesis of 1,2-Benzo[ e]thiazine and Benzo[ d]thiazole Analogues Containing a S-Trifluoromethyl Sulfoximine Group: Preparation and New Properties of the Adachi Reagent.

We report here the preparation of unprecedented analogues of 1,2-benzothiazine and benzoisothiazole incorporating the S-trifluoromethyl sulfoximine group in their core. Using a stable precursor to start, cyclization occurs via a catalytic controlled process. The choice of the catalyst is crucial for selectivity toward the five- or the six-membered ring. Interestingly, one of the benzothiazines can be converted on a gram scale into the trifluoromethylating Adachi reagent. We also disclose the first use of this reagent as a source of radical CF3 under photoredox catalysis. DFT calculations were performed to clarify the cyclization mechanism.

Chiral Organocatalyzed Intermolecular Rauhut-Currier Reaction of Nitroalkenes with Ethyl Allenoate.

An enantioselective intermolecular Rauhut-Currier (RC) reaction of nitroalkenes with ethyl allenoate has been established with quinidine-derived ß-isocupreidine. The present RC reaction afforded α-functionalized allenoates 3 in up to 94% yield with 59% enantiomeric excess (ee).

First isolation of enantiopure perfluoroalkylated sulfilimines and sulfoximines.

Mono-, di- and trifluoromethyl sulfilimines and sulfoximines have been isolated for the first time in enantiopure form by separation of the racemate by supercritical fluid chromatography. The electrophilic trifluoromethylating Shibata reagent has been prepared as a single enantiomer.

Auto tandem triple cascade organocatalysis: access to bis-lactone and butenolide derivatives.

The synthesis of bis-lactone and butenolide derivatives was described using alkylidene Meldrum's acid as nucleophiles. The process operates in a triple cascade through an auto tandem catalysis promoted by DBU.

Correction: An efficient and recyclable ionic diphosphine-based Ir-catalyst for hydroaminomethylation of olefins with H2O as the hydrogen source.

Correction for 'An efficient and recyclable ionic diphosphine-based Ir-catalyst for hydroaminomethylation of olefins with H2O as the hydrogen source' by Huan Liu et al., Chem. Commun., 2018, 54, 7979-7982.

An efficient and recyclable ionic diphosphine-based Ir-catalyst for hydroaminomethylation of olefins with H2O as the hydrogen source.

Hydroaminomethylation of olefins with H2O as the hydrogen source was accomplished over an Ir-catalyst with the involvement of an ionic diphosphine (L6). The use of H2O as the hydrogen source could completely inhibit the hydrogenation of olefins. The π-accepting ability and improved stability of L6 endowed the corresponding Ir-catalyst with high activity and good longevity for recycling uses.

Imidazolium-Based Ionic Liquids as Efficient Reagents for the C-O Bond Cleavage of Lignin.

The demethylation of lignin in ionic liquids (ILs) was investigated by using pure lignin model monomers and dimers together with dioxane-isolated lignins from poplar, miscanthus, and maize. Different methylimidazolium ILs were compared and the samples were treated with two different heating processes: microwave irradiation and conventional heating in a sealed tube. The conversion yield and influence of the treatment on the lignin structure were assessed by 31 P NMR spectroscopy, size-exclusion chromatography, and thioacidolysis. The acidic methylimidazolium IL [HMIM]Br was shown to be an effective combination of solvent and reagent for the demethylation and depolymerization of lignin. The relatively mild reaction conditions, the clean work-up, and the ability to reuse the IL makes the described procedure an attractive and new green method for the conversion of lignin to produce phenol-rich lignin oligomers.

Asymmetric aza-Diels-Alder reaction of Danishefsky's diene with imines in a chiral reaction medium.

The asymmetric aza-Diels-Alder reaction of chiral imines with Danishefsky's diene in chiral ionic liquids provides the corresponding cycloadduct with moderate to high diastereoselectivity. The reaction has proved to perform better at room temperature in ionic liquids without either Lewis acid catalyst or organic solvent. Chiral ionic liquids are recycled while their efficiency is preserved.

S-Trifluoromethyl Sulfoximine as a Directing Group in Ortho-Lithiation Reaction toward Structural Complexity.

The first use of the NH S-trifluoromethyl sulfoximine as an ortho directing group is described for the functionalization of the aryl group bonded to the sulfur atom. Various electrophiles (halogen, carbon, oxygen, sulfur, boron, etc.) are introduced on the aromatic ring. Cyclic S-trifluoromethyl sulfoximines are synthesized either with properly chosen electrophiles or by structural adjustment of o-azido sulfoximines. Fluorinated analogues of prazosin are also prepared.

Solvent-free condensation of phenylacetonitrile and nonanenitrile with 4-methoxybenzaldehyde: optimization and mechanistic studies.

The condensation of phenylacetonitrile with 4-methoxybenzaldehyde can be carried out by two solvent-free methods: i) using neat powdered KOH at room temperature with equivalent amounts of aldehyde, nitrile and base for 3 min, and ii) using K2CO3 in the presence of a phase transfer agent for 3 min under microwave activation or conventional heating. By extending the reaction time up to 10 min, four different products were obtained from phenyl or nitrile group migration. With nonanenitrile, only the second method could be applied to give two kinds of condensed compounds with or without phenyl (or nitrile) group migration. The intervention of non-thermal MW-specific effects was proved in some cases and interpreted.

NMR spectroscopic data of some 1-alkoxy-2,2-di(carbonyl, carboxyl, cyano)-substituted ethylenes.

The 1H-13C NMR shifts as well as 1H and 13C coupling constants of 14 alkoxymethylene malonic acid and acetoacetic acid derivatives and two alkoxymethylene acetylacetones are reported. The 17O NMR spectra have been recorded for six of them. The long-range coupling 3J(H-C=C-C(R)) has been used for determining the stereochemistry of the double bond.

A possible improvement for structure-based drug design illustrated by the discovery of a Tat HIV-1 inhibitor.

The HIV-1 Tat protein is a promising target for AIDS therapy, due to its extra-cellular roles against the immune system. From the 2D-NMR structure of Tat, we have designed molecules, called TDS, able to bind to Tat and inhibit HIV-1 replication in vitro. This new family of antivirals is composed of a triphenylene aromatic ring substituted with at least one carbon chain bearing a succinimide group. These ligands are prepared from triphenylene or 2,6,10-trimethylphenylene in 3-6 steps depending on the target molecule.