Chiral Cyclopropenimine-catalyzed Asymmetric Michael Addition of Bulky Glycine Imine to α,ß-Unsaturated Isoxazoles.

A highly efficient asymmetric Michael addition of bulky glycine imine to α,ß-unsaturated isoxazoles has been achieved by using 5 mol% of chiral cyclopropenimine as a chiral organo-superbase catalyst under mild conditions. Michael adducts were obtained in excellent yields (up to 97%) and stereoselectivities (up to >99 : 1 dr and 98% ee). A significant solvent effect was found in these chiral organosuperbase catalyzed asymmetric Michael reactions. Gram-scale preparation of Michael adducts and their transformations are realized to provide corresponding products without loss of stereoselectivities. The configurations of Michael adduct was determined by single-crystal X-ray diffraction analysis.

Visible-light driven synthesis of polycyclic benzo[d][1,3]oxazocine from 2-aminochalcone.

Herein, we report a tandem cycloisomerization/nucleophilic addition/cyclization of 2-amino chalcone with bifunctional nucleophiles driven by visible light. This cascade process is realized by the irradiation of a blue LED at room temperature, which provides a concise route to structurally diverse benzo[d][1,3]oxazocine scaffolds. Mechanistic studies show that the reaction is initiated with the E to Z isomerization of a C-C double bond upon the irradiation of visible light, followed by cyclization/rearomatization to generate a transient quinolinium intermediate, which is trapped by the nucleophile and cyclized to produce the polycyclic benzo[d][1,3]oxazocine.

Bioactive constituents from Salacia cochinchinensis.

Two new isopimarane diterpenoids, named 1α-hydroxy-7-oxoisopimara-8, 15-diene (1), 11ß-hydroxy-7-oxoisopimara-8(14), 15-diene (2), together with six known compounds (3-8), were isolated from the medicinal plant Salacia cochinchinensis. All isolates were assayed for their cytotoxicity and α-glucosidase inhibitory activity. Results suggested compounds 1, 3 possessed significant cytotoxic activity against HepG2, HL60, and Hela cell lines with IC50 values ranging from 0.23 to 0.35 µM, and compounds 7, 8 exhibited noticeable α-glucosidase inhibitory ability with IC50 values of 0.25 and 0.31 µM, respectively.

A bio-inspired synthesis of hybrid flavonoids from 2-hydroxychalcone driven by visible light.

A bio-inspired synthesis of hybrid flavonoids from 2-hydroxylchalcone is described. Under the irradiation of 24 W CFL, 2-hydroxychalcone reacts with various nucleophiles to deliver structurally diverse hybrid flavonoids in good to excellent yields in the presence of a catalytic Brønsted acid. Moreover, moderate enantioselectivities could be obtained using a catalytic chiral phosphoric acid via counter anion directed addition. Based on mechanistic studies, the reaction is proposed to proceed via tandem double-bond isomerization/dehydrated cyclization of 2-hydroxychalcone to form a transient flavylium cation, which is in situ captured by nucleophiles to afford hybrid flavonoids.

A Family of Energetic Materials Based on 1,2,4-Oxadiazole and 1,2,5-Oxadiazole Backbones With Low Insensitivity and Good Detonation Performance.

Design and synthesis of new compounds with both high detonation performances and good safety properties have always been a formidable task in the field of energetic materials. By introducing -ONO2 and -NHNO2 moieties into 1,2,4-oxadiazole- and 1,2,5-oxadiazole-based backbones, a new family of energetic materials, including ammonium 3-nitramino-4-(5-hydroxymethyl-1,2,4-oxadiazol-3-yl)-furazan (4), 3,3'-bis[5-nitroxymethyl-1,2,4-oxadiazol-3-yl]-4,4'-azofuroxan (6), [3-(4-nitroamino-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5-yl]-methylene nitrate (8), and its energetic ionic salts (10-12), were synthesized and fully characterized. The energetic and physical properties of the materials were investigated through theoretical calculations and experimental determination. The results show that the oxadiazole-based compounds exhibit high enthalpy of formations, good detonation performances, and extraordinary insensitivities. In particular, the hydrazinium salt (11) shows the best energetic properties (11: d = 1.821 g cm-3; P = 35.1 GPa, v D = 8,822 m s-1, IS = 40 J, FS > 360N). The ESP and Hirshfeld surface analysis indicated that a large number of hydrogen bonds as well as π-π stacking interactions within molecules might be the key reason for their low sensitivities and high energy-density levels.

Bioactive spirans and other constituents from the leaves of Cannabis sativa f. sativa.

In this paper, 17 compounds (1-17) were isolated from the leaves of Hemp (Cannabis sativa f. sativa). Among the isolates, two were determined to be new spirans: cannabispirketal (1), and α-cannabispiranol 4'-O-ß-D-glucopyranose (2) by 1D and 2D NMR spectroscopy, LC-MS, and HRESIMS. The known compounds 7, 8, 10, 13, 15, and 16 were isolated from Hemp (C. sativa f. sativa) for the first time. Furthermore, compounds 8 and 13 were isolated from the nature for the first time. All isolated compounds were evaluated for cytotoxicity on different tissue-derived passage cancer cell lines through cell viability and apoptosis assay. Among these compounds, compounds 5, 9 and 16 exhibited a broad-spectrum antitumor effect via inhibiting cell proliferation and promoting apoptosis. These results obtained have provided valuable clues to the understanding of the cytotoxic profile for these isolated compounds from Hemp (C. sativa f. sativa).

6,8-Di-bromo-3-nitro-2-phenyl-2H-chromene.

In the title compound, C15H9Br2NO3, the chromene unit is not quite planar (r.m.s. deviation from planarity = 0.0888 Å). The di-hydro-pyran ring adopts an envelope conformation with the phenyl-substituted C atom fused to the di-hydro-pyran ring as the flap. The dihedral angle between the plane defined by this C atom and the adjacent C and O atoms and the mean plane of the di-hydro-pyran ring excluding the phenyl-substituted C atom is 25.1 (3)°. The dihedral angle between the mean plane of the chromene unit and the phenyl ring is 85.7 (1)°. The crystal structure features C-H⋯O hydrogen bonds and Br⋯O contacts [3.289 (3) Å] involving the nitro O atoms.

Isopropyl 3-phenyl-isoxazole-5-carboxyl-ate.

In the title compound, C13H13NO3, the isoxazole ring is approximately coplanar with the phenyl ring, the dihedral angle between their planes being 7.37 (19)°. In the crystal, centrosymmetrically related mol-ecules are linked into dimers by pairs of C-H⋯O hydrogen bonds, generating a ring of graph-set motif R 2 (2)(10).

One-pot tandem cyclization of enantiopure asymmetric cis-2,5-disubstituted pyrrolidines: Facile access to chiral 10-heteroazatriquinanes.

A series of chiral 10-heteroazatriquinanes were synthesized from enantiopure asymmetric cis-2,5-disubstituted pyrrolidines through a one-pot tandem cyclization procedure. The structures and configurations of these new chiral 10-heteroazatriquinanes are confirmed by X-ray single-crystal diffraction analysis.

Efficient synthesis of unnatural dipeptides based on cis-2,5-disubstituted pyrrolidine.

The well-defined unnatural dipeptides based on cis-2,5-disubstituted pyrrolidine backbone were synthesized from commercially available starting materials meso-diethyl-2,5-dibromoadipate, (S)-(-)-1-phenylethylamine, and phenylalanine. The configurations of all the chiral centers in these unnatural dipeptides are confirmed by X-ray crystal diffraction analysis.

Ethyl 4-benzamido-5-phenyl-4H-1,2,4-triazole-3-carboxyl-ate monohydrate.

In the title compound, C(18)H(16)N(4)O(3)·H(2)O, the dihedral angles between the triazole ring and the phenyl rings are 84.8 (4) and and 39.8 (4)°. The phenyl rings make a dihedral angle of 84.5 (9)°. In the crystal, the molecules are linked by N-H⋯O and O-H⋯N hydrogen bonds. An intra-molecular O⋯N inter-action also occurs [2.827 (3) Å].

Synthesis and application of a novel single-isomer mono-6-deoxy-6-((2S,3S)-(+)-2,3-O-isopropylidene-1,4-tetramethylenediamine)-ß-cyclodextrin as chiral selector in capillary electrophoresis.

A novel single isomer of positively charged ß-cyclodextrin, mono-6-deoxy-6-((2S,3S)-(+)-2,3-O-isopropylidene-1,4-tetramethylenediamine)-ß-CD (MIPTACD) was designed and synthesized in seven steps starting from commercially available (2R,3R)-tartaric acid. The chiral resolution abilities of the new cationic chiral selector were studied by capillary electrophoresis using 10 different dansyl (Dns)-amino acids and N-acetylphenylalanine (N-Ac-Phe) as model analytes. The effects of running buffer pH and chiral selector concentration on the separation selectivity, resolutions, and migration times of analytes were studied in detail. MIPTACD shows a very good chiral recognition ability even at very low concentrations at the investigated pH values, as shown by the very large values of selectivity and resolution towards amino acids enantiomers to be assessed.

Synthesis of chiral vicinal diols and analysis of them by capillary zone electrophoresis.

This paper describes an improved access to 1,4-bis (9-O-quininyl) phthalazine [(QN)(2)PHAL], a very useful chiral ligand for catalytic asymmetric dihydroxylation (AD), by using CaH(2) as acid-binding reagent in a high yield under mild conditions. The application of (QN)(2)PHAL to the AD reactions of eight olefins exhibited excellent enantioselectivity and activity with corresponding chiral vicinal diols. Furthermore, a capillary zone electrophoresis method was developed to separate the aforementioned chiral vicinal diols by using of neutral beta-cyclodextrin (beta-CD) as chiral selector and borate as running buffer. High resolution was achieved under the optimal conditions of beta-CD 2.2% (w/v), pH 10, 200 mM borate buffer at 15 kV, and 20 degrees C within 15 min. The relative standard deviations of the corrected peak areas and migration time were less than 3.9% and 1.3%, respectively. In addition, the developed method was successfully applied to the determination of the purity and the enantiomeric excesses value (%ee) of the AD reaction products.

Facile synthetic route to enantiopure unsymmetric cis-2,5-disubstituted pyrrolidines.

The (+/-)-cis-5-arylcarbamoyl-2-ethoxycarbonylpyrrolidines 6a-g were firstly synthesized in 53-64% yields by using meso-diethyl-2,5-dibromoadipate 3 and (S)-(-)-1-phenylethylamine in three steps. The diastereomeric mixture (S;2S,5R)-(-)-7 and (S;2R,5S)-(+)-8 were prepared by the Grignard reaction and separated by a flash column chromatography in 29 and 52% yields. The absolute configurations of (+)-8 was confirmed by X-ray crystallographic analysis and the enantiopure pyrrolidines (2S,5R)-(-)-9/(2R,5S)-(+)-9 and (2S,5R)-(-)-10/(2R,5S)-(+)-10 were obtained in good yields.

Determination of enantiomeric excess for 2,3-dihydroxy-3-phenylpropionate compounds by capillary electrophoresis using hydroxypropyl-beta-cyclodextrin as chiral selector.

A new capillary zone electrophoresis (CZE) method was developed to separate three chiral 2,3-dihydroxy-3-phenylpropionate enantiomers using neutral hydroxypropyl-beta-CD (HP-beta-CD) as chiral selector and borate as background electrolyte. The results showed that HP-beta-CD exhibited good enantioselectivity and high resolution was achieved under the optimum condition of pH 10.3, 200 mM borate buffer containing 6% methanol and 50 mM HP-beta-CD at 15 kV and 20 degrees C within 16 min. The precision of the method was <0.9% for migration time and 4.5% for corrected peak area. In addition, the developed method was successfully applied to the determination of enantiomeric excess (ee) of synthetic 2,3-dihydroxy-3-phenylpropionate samples. With this method, low as 0.2% impurity of the undesirable enantiomer in the presence of high amount of target enantiomer was determined. The results demonstrated that the proposed CZE method is a simple and useful technique and is applicable to ee assay of 2,3-dihydroxy-3-phenylpropionate enantiomers.

Investigation on 1,4-dichlorophthalazine-derivatized cinchona alkaloids-catalyzed asymmetric "interrupted" Feist-Bénary reaction.

Different 1,4-dichlorophthalazine-cinchona alkaloid derivatives have been used to catalyze the asymmetric "interrupted" Feist-Bénary reaction of ethyl bromopyruvate/substituted bromoketoesters and beta-dicarbonyl compounds. The corresponding hydroxydihydrofurans have been obtained in excellent yields and with up to 91%ee.

Analysis of optical purity and impurity of synthetic D-phenylalanine products using sulfated beta-cyclodextrin as chiral selector by reversed-polarity capillary electrophoresis.

A new capillary electrophoresis (CE) method has been achieved for simultaneous separation and quantification of phenylalanine, N-acetylphenylalanine enantiomers, and prochiral N-acetylaminocinnamic acid, possibly co-existent in reaction systems or synthesized products of D-phenylalanine. The separation was carried out in an uncoated capillary under reversed-electrophoretic mode. Among the diverse charged cyclodextrins (CDs) examined, highly sulfated (HS)-beta-CD as the chiral selector exhibited the best enantioselectivity. The complete separation of the analytes was obtained under the optimum conditions of pH 2.5, 35 mM Tris buffer containing 4% HS-beta-CD, applied voltage -15 kV, and capillary temperature 25 degrees C. Furthermore, the proposed method was applied to the determination of optical purity and trace impurities in three batches of the asymmetric synthetic samples of D-phenylalanine, and satisfactory results were obtained. The determination recoveries of the samples were in the range of 97.8-103.8%, and precisions fell within 2.3-5.0% (RSD). The results demonstrate that this CE method is a useful, simple technique and is applicable to purity assays of D-phenylalanine.