Base- and sulfur-promoted oxidative lactonization of chalcone-acetate Michael adducts: access to pyran-2-ones.

A cost-effective, practical, straightforward and scalable synthesis of α-pyrones via base- and sulfur-promoted annulation of phenylacetates and chalcones is reported. Generated in situ from the starting components by using dbu as a base catalyst, the Michael adducts underwent a smooth oxidative cyclization into 3,4,6-triaryl-2-pyranones upon heating with DABCO and sulfur in DMSO. Extension to malonate in place of phenylacetates led to 4,6-diaryl-2-pyranone-2-carboxylates.

Sulfur-Promoted Oxidative Condensation of Chalcones with Unsubstituted Cyanoacetamide in DMSO: Access to 3-Cyanopyrid-2-ones.

Elemental sulfur and DABCO were found to be an excellent combination to promote a one-pot cascade of condensation-oxidative cyclization of chalcones and unsubstituted cyanoacetamide in DMSO to provide 3-cyanopyrid-2-ones.

Reaction of 1-acetonaphthones with anilines and elemental sulfur: rapid construction of 1-anilinonaphtho[2,1-b]thiophenes.

1-Anilinonaphtho[2,1-b]thiophenes could be conveniently synthesized from a three-component reaction of 1-acetonaphthones with anilines and elemental sulfur under catalyst-free simple heating conditions.

Base-catalyzed multicomponent access to quinoxalin-2-thiones from o-phenylenediamines, aryl ketones and sulfur.

3-Arylquinoxaline-2-thiones were conveniently synthesized via three-component oxidative condensation of acetophenones with o-phenylenediamines and sulfur in DMSO in the presence of piperidine as a catalyst. The products could be readily isolated from the reaction mixture by simple precipitation and washing with methanol. This set of reaction conditions applied to higher homologs of acetophenones as well as benzyl phenyl ketones led to 2,3-di-C-substituted quinoxalines. Further functionalization of 3-phenylquinoxaline-2-thione via reaction on the thione group could be readily performed to provide quinoxaline derivatives in good yields.

Base-Catalyzed Three-Component Reaction of α-Cyanoacetates with Chalcones and Elemental Sulfur: Access to 2-Aminothiophenes Unobtainable via the Gewald Reaction.

Although the Gewald reaction was well-known for more than half a century as an excellent method providing bioactive 2-aminothiophenes from reactions of α-cyanoacetates and carbonyl compounds and elemental sulfur, its application to dibenzoylmethanes as the carbonyl substrates was, however, unknown and experimentally proven unsuccessful. We propose here a convenient approach to such a series of compounds by a DABCO-catalyzed, one-pot, two-step, three-component reaction of α-cyanoacetate with chalcones and elemental sulfur. This catalytic strategy is highlighted by its excellent atom/step efficiency and high degree of structural diversification by simply choosing the suitable starting chalcones, which are unarguably much more readily available than dibenzoylmethanes.

Room-Temperature Synthesis of Tetrasubstituted 1,3-Dithioles by Dimerizing Sulfuration of Chalcones with Elemental Sulfur.

Chalcones were found to undergo sulfurative dimerization with elemental sulfur to tetrasubstituted 1,3-dithioles. The reaction was found to proceed at room temperature in the presence of a nitrogen-base catalyst in DMSO.

Access to [2,1]Benzothiazine S,S-Dioxides from ß-Substituted o-Nitrostyrenes and Sulfur.

[2,1]Benzothiazine S,S-dioxides 2 were synthesized by simply heating o-nitrostyrenes with elemental sulfur in 3-picoline with complete atom economy. This reaction was found to occur without any added catalyst and consist of a cascade of reduction of the nitro group, sulfuration of a C-H of the double bond, oxidation of a sulfur atom to its highest oxidation state by the migration of two oxygen atoms from the nitro group, and formation of new N-S bonds. Furthermore, the method could also be applied to o-nitrocinnamamides and cinnamate esters.

α-Glucosidase Inhibitory Depsidones from the Lichen Parmotrema tsavoense.

Chemical investigation of the lichen Parmotrema tsavoense led to the isolation of 5 new depsidones, parmosidones F - J (1:  - 5: ). These compounds were structurally elucidated using spectroscopic methods including HRESIMS and 2D NMR data. Compounds 1, 3: , and 4: were evaluated for their inhibition of α-glucosidase. All exhibited potent α-glucosidase inhibitory activity with IC50 values ranging from 10.7 to 17.6 µM, which was much lower than that of the positive control acarbose (IC50 449 µM).

Salazinic Acid-Derived Depsidones and Diphenylethers with α-Glucosidase Inhibitory Activity from the Lichen Parmotrema dilatatum.

Three new depsidones, parmosidones F - G (1 - 2), and 8'-O-methylsalazinic acid (3), and 3 new diphenylethers, parmetherines A - C (4 - 6), together with 2 known congeners were isolated from the whole thalli of Parmotrema dilatatum, a foliose chlorolichen. Their structures were unambiguously determined by extensive spectroscopic analyses and comparison with literature data. The isolated polyphenolics were assayed for their α-glucosidase inhibitory activities. Newly reported benzylated depsidones 1: and 2: in particular inhibited α-glucosidase with IC50 values of 2.2 and 4.3 µM, respectively, and are thus more potent than the positive control, acarbose.

Convenient one-pot access to 2H-3-nitrothiochromenes from 2-bromobenzaldehydes, sodium sulfide and ß-nitrostyrenes.

An efficient synthesis of 2H-3-nitrothiochromenes via a cascade reaction was established. Starting from commercially available o-bromobenzaldehydes and ß-nitrostyrenes with sodium sulfide nonahydrate as an inexpensive sulfur source, various substituted thiochromenes were synthesized with high functional group tolerance without any added transition metal catalyst or additive.

Sulfonic Acid-Containing Flavonoids from the Roots of Phyllanthus acidus.

Six new sulfonic acid-containing flavonoids, acidoflavanone (1), acidoauronol (2), 5- O-methylacidoauronol (3), acidoaurone (4), acidoisoflavone (5), and acidoflavonol (6), were isolated from the EtOH extract of the roots of Phyllanthus acidus. Their structures were unambiguously established by interpretation of their HRESIMS and 1D and 2D NMR data, single-crystal X-ray diffraction analysis, and comparison to the literature data. These new structures represent the first examples of sulfonic acid-containing flavanones, auronols, aurones, and isoflavones.

Crystal structure of 4-(naphthalen-2-yl)-2-oxo-6-phenyl-1,2-di-hydro-pyridine-3-carbo-nitrile.

The synthesis and crystal structure of the title compound, C22H14N2O, are described. The title compound was synthesized by a three-component one-pot reaction in DMSO involving chalcone, cyano-acetamide and elemental sulfur as catalyst. The compound was characterized by spectroscopic methods and single-crystal X-ray diffraction. The structure consists of inversion-related dimers produced by N-H⋯O hydrogen bonding, which further inter-act through π-π contacts.

Sulfur-Promoted Oxidative Cyclization of Pentan-1-ones: Direct Access to Tetrasubstituted Furans from Deoxybenzoins and Chalcones.

Furan is an important heterocyclic scaffold in natural product, bioorganic, and medicinal chemistry as well as in materials science. The system S8/DABCO/DMSO was found to efficiently mediate the oxidative cyclization of 1,2,3,5-tetraarylpentan-1-ones A, which were obtained in situ as the Michael adducts of chalcones 1 and deoxybenzoins 2, to furan 3. The strategy provided convenient and direct access to tetrasubstituted furans 3 from readily available starting materials with high functional group tolerance.

DABCO-Catalyzed DMSO-Promoted Sulfurative 1,2-Diamination of Phenylacetylenes with Elemental Sulfur and o-Phenylenediamines: Access to Quinoxaline-2-thiones.

The oxidative amination of alkynes typically requires transition metal catalysts and strong oxidants. Herein, we alternatively utilize DABCO as a sulfur-activating catalyst to achieve the sulfurative 1,2-diamination of phenylacetylenes with elemental sulfur and o-phenylenediamines. DMSO was found to be particularly suitable for use as a terminal oxidant for this three-component process. A mechanistic study has shown that this cascade reaction is triggered by the addition of active sulfur species to the triple bond of phenylacetylenes.

A new labdane-type diterpenoid from the leaves of Vitex negundo L.

A new labdane-type diterpenoid, named vitexnegundin (1), along with seven known compounds, including vitexilactone (2), vitetrifolin D (3), 13-hydroxy-5(10),14-halimadien-6-one (4), (rel 3S,5S,8R,9R,10S)-3,9-dihydroxy-13(14)-labden-16,15-olide (5), artemetin (6), vitexcarpin (7) and penduletin (8), were isolated from the leaves of Vitex negundo L. Their structures were elucidated by using spectroscopic methods, X-ray crystallographic analysis and comparison with those reported in the literature. Moreover, all isolated compounds 1-8 were evaluated for their antimicrobial activity against ESBL-producing Escherichia coli strain and methicillin-resistant Staphylococcus aureus.

Synthesis and cytotoxic evaluation of usnic acid benzylidene derivatives as potential anticancer agents.

A series of usnic acid benzylidene derivatives (groups I-V) were designed, synthesized and evaluated for their anticancer activity in the search for potentially new anticancer agents. Compounds 1a, 5b, 2b, 2e and 2f exhibited the most potent cytotoxcity against K562 cell line with IC50 values of 10.0 ± 3.6, 5.6 ± 0.4, 8.8 ± 1.0, 4.5 ± 0.1 and 8.4 ± 0.4 µM, respectively. It is noteworthy that compound 2e displayed potent cytotoxicity against K562 cells without any cytotoxic effect on HEK293 normal cell line.

Synthesis and crystal structure of peptide dimethyl biphenyl hybrid C52H60N6O10·0.25H2O.

The synthesis and crystal structure of peptide 6,6'-dimethyl biphenyl hybrid are described. The title compound was synthesized by reaction between 6,6'-dimethyl-[1,1'-biphen-yl]-2,2'-dicarbonyl dichloride in CH2Cl2, amine HN-proline-phenyl-alanine-alanine-COOMe and Et3N at 273 K under N2 atmosphere and characterized by single-crystal X-ray diffraction. The asymmetric unit contains one peptide mol-ecule and a quarter of a water mol-ecule. A disorder of a methyl and meth-oxy-carbonyl group of one alanine residue is observed with occupancy ratio 0.502 (6):0.498 (6). The structure is consolidated by intra- and inter-molecular hydrogen bonds.

Crystal structure of a tripeptide biphenyl hybrid C50H56N6O10·0.5H2O.

A peptide biphenyl hybrid compound {systematic name: dimethyl 2,2'-[((2S,2'S)-2,2'-{[(2S,2'S)-1,1'-([1,1'-biphen-yl]-2,2'-dicarbon-yl)bis-(pyrrolidine-1,2-diyl-2-carbon-yl)]bis-(aza-nedi-yl)}bis-(3-phenyl-propano-yl))bis-(aza-nedi-yl)](2S,2'S)-dipropionate hemihydrate}, C50H56N6O10·0.5H2O, was prepared by coupling of [1,1'-biphen-yl]-2,2'-dicarbonyl dichloride, tri-ethyl-amine and the tripeptide Pro-Phe-Ala in CH2Cl2 at 273 K under an N2 atmosphere. In the crystal, the asymmetric unit contains the peptide biphenyl hybrid accompanied by one-half of a water mol-ecule. A C atom of one of the proline rings is disordered between two positions in a 0.746 (11):0.254 (11) ratio. An important structural aspect of peptide compounds is their capacity to self-associate mediated by inter-molecular and intra-molecular hydrogen bonding. This characteristic can be useful in understanding the inter-actions between peptides and biomacromolecular targets, as well as to explain peptide properties.

Crystal structures of 2-(2-bromo-5-fluoro-phen-yl)-8-eth-oxy-3-nitro-2H-thio-chromene and 2-(2-bromo-5-fluoro-phen-yl)-7-meth-oxy-3-nitro-2H-thio-chromene.

Two thio-chromene com-pounds containing Br and F atoms, namely 2-(2-bromo-5-fluoro-phen-yl)-8-eth-oxy-3-nitro-2H-thio-chromene (C17H13BrFNO3S, A) and 2-(2-bromo-5-fluoro-phen-yl)-7-meth-oxy-3-nitro-2H-thio-chromene (C16H11BrFNO3S, B), were prepared via the condensation reaction between 2-mer-capto-benzaldehyde and nitro-styrene derivatives. In both com-pounds, the thio-chromene plane is almost perpendicular to the phenyl ring. In the structure of A, mol-ecules are assembled via π-π stacking and C-H⋯O and C-F⋯π inter-actions. In the crystal packing of B, mol-ecules are linked by C-H⋯F, C-H⋯O, C-H⋯π and π-π inter-actions.

Further terpenoids from Euphorbia tirucalli.

The phytochemical investigation of Euphorbia tirucalli L. (Euphorbiaceae) yielded four new compounds, including a rare cadalene-type sesquiterpene (tirucadalenone), two tirucallane triterpenoids, euphorol L and euphorol M, with the latter being described as an epimeric mixture, and a euphane triterpene, namely, euphorol N, together with 7 known compounds. Their structures and absolute configurations were elucidated from analysis of 1D (1H, J-modulated 13C) and 2D NMR (HSQC, HMBC and NOESY), high-resolution mass spectrometry (HRESIMS), optical rotation, and GIAO NMR shift calculation followed by CP3 analysis, along with comparison with literature reports. All these compounds were tested for cytotoxicity against K562, MCF-7 and/or and HepG2 tumor cell lines. Only tirucadalenone displayed a mild cytotoxic activity.