Shengyong Zhang

Highly Enantioselective Nitro-Mannich Reaction Catalyzed by Cinchona Alkaloids and N-Benzotriazole Derived Ammonium Salts

The catalytic enantio- and diastereoselective nitro-Mannich reaction of α-amido sulfones in the mixed solvent of toluene/H(2)O has been realized using a phase-transfer catalyst (PTC) derived from cinchona alkaloids and N-benzotriazole. It performed well over a wide range of substrates to give the desired products in good yields (up to 94%) with excellent enantioselectivities (up to 99% ee) and diastereoselectivities (up to 99:1).

Autophagy stimulates apoptosis in HER2‐overexpressing breast cancers treated by lapatinib

HER2‐overexpressing breast cancers often show hyperactivation of the HER2/AKT/mTOR signaling pathway. Lapatinib is an oral dual tyrosine kinase inhibitor (TKI) that targets both EGFR and HER2 to inhibit the proliferation of breast cancer cells. However, it is obscure whether and how lapatinib could induce autophagy in breast cancer cells, an important cell response with drug treatment. In this study, we investigated the apoptosis and the autophagy in the HER2‐overexpressing breast cancer cells BT474 and AU565 treated with lapatinib, and further examined their relationship. Lapatinib inhibited the proliferation and the rate of DNA synthesis in HER2‐positive cells, as observed by MTT, colony formation and EDU assays. Lapatinib not only induced apoptosis accompanied by an increased expression of cleaved Caspase‐3 and cleaved PARP, but it also induced autophagy in vitro, as confirmed by electron microscopy (EM), acridine orange (AO) staining and LC3‐II expression. Meanwhile, lapatinib inhibited the phosphorylation of HER2, AKT, mTOR, and p70S6K, whereas that of AMPK was activated. When the cells were pre‐incubated with 3‐Methyladenine (3‐MA), the specific autophagy inhibitor, the growth inhibitory ratio and apoptosis rate were frustrated, whereas colony formation and DNA synthesis ability were encouraged. In addition, 3‐MA application could up‐regulate Caspase‐3 and PARP expression, compared with the treatment with lapatinib alone. The addition of 3‐MA could attenuate the inhibitory role on HER2/AKT/mTOR pathway and the active role on AMPK that was raised by lapatinib. Therefore, lapatinib simultaneously induced both apoptosis and autophagy in the BT474 and AU565 cells, and in these settings, autophagy facilitates apoptosis. J. Cell. Biochem. 114: 2643–2653, 2013.

Bifunctional ferrocene-based squaramide-phosphine as an organocatalyst for highly enantioselective intramolecular Morita–Baylis–Hillman reaction

This work demonstrates that, in accord with metal catalysis, ferrocene could be an excellent scaffold for organocatalysts. The simple and easily accessible bifunctional ferrocene-based squaramide-phosphine shows high enantioselectivity in the intramolecular Morita-Baylis-Hillman reaction of 7-aryl-7-oxo-5-heptenals, giving a variety of 2-aroyl-2-cyclohexenols in up to 96% ee.

Ferrocene as a scaffold for effective bifunctional amine–thiourea organocatalysts

A simple and readily accessible prototype of the ferrocene-based bifunctional amine–thioureas shows high enantioselectivity in the Michael addition of acetylacetone to nitroolefins, giving the enantioselectivity of up to 96% ee. This work demonstrates that, in accord with metal catalysis, ferrocene could be an excellent scaffold for chiral organocatalysts.

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

A novel single isomer of positively charged β-cyclodextrin, mono-6-deoxy-6-((2S,3S)-(+)-2,3-O-isopropylidene-1,4-tetramethylenediamine)-β-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.

Enantioselective separation of chiral vicinal diols in capillary electrophoresis using a mono‐6A‐aminoethylamino‐β‐cyclodextrin as a chiral selector

This paper describes an improved access to mono-6(A)-aminoethylamino-beta-CD (beta-CDen), a very efficient cationic chiral selector for CZE in the separation of eight chiral aromatic vicinal diols. The beta-CDen concentration has a strong influence on the efficiency of enantioseparation. The effects of the pH and concentration of the BGE, the capillary temperature, and the applied voltage on the resolution and separation selectivity have been studied. Excellent chiral resolution was achieved under the optimal conditions of beta-CDen 10 mM, pH 10, 200 mM borate buffer at 15 kV and 20 degrees C within 20 min. Moreover, the developed method was successfully applied to the determination of the enantiomeric purity of the catalytic asymmetric dihydroxylation (AD) reaction products.

A new approach to the synthesis of (−)-2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane(diop)

Abstract (–)-2,3-0-Isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane (DIOP) has been prepared by reaction of (−)-1,2:3,4-diepoxybutane with lithium diphenylphosphide followed by ketalisation with 2,2-dimethoxypropane.

Highly modular dipeptide-like organocatalysts for direct asymmetric aldol reactions in brine

A novel series of dipeptide-like organocatalysts derived from proline, amino acids and primary amines have been prepared for direct asymmetric aldol reactions between various aromatic aldehydes and acetone to afford aldol products in good yields (up to 82%) and moderate enantioselectivities (up to 67% ee) with only 1 mol% of catalyst-loading in brine. Under the same conditions, the direct asymmetric aldol reactions of aromatic aldehydes and cyclohexanone give aldol products with high yields (up to 91%) and moderate to good enantioselectivities (up to 88% ee) and excellent diastereoselectivities (up to 99% dr). These organocatalysts are easily synthesized from commercially available materials in multi-gram scale with high modularity in their structural and stereogenic properties.

Facile Total Synthesis of Xanthotoxol

Abstract Xanthotoxol, a biologically active linear furocoumarin, has been efficiently synthesized from 7‐hydroxycoumarin in six steps. The key steps included two efficient rearrangements—Fries rearrangement and Claisen rearrangement—and a Baeyer–Villiger oxidation process. The overall yield of xanthotoxol was 29%. This approach also provided a new strategy to furnish easily furocoumarins with a hydroxyl group in the framework.

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 molecules are linked into dimers by pairs of C—H⋯O hydrogen bonds, generating a ring of graph-set motif R 2 2(10).