Enantioselective Synthesis of Functionalized Tetrahydropyridines through Iridium-Catalyzed Formal [5+1] Annulation.

An efficient iridium-catalyzed asymmetric formal [5+1] annulation by in situ generation of enamines as N-nucleophiles for the synthesis of tetrahydropyridine derivatives is disclosed. The methodology offers direct access to a wide variety of chiral tetrahydropyridine derivatives in moderate to good yields and excellent enantioselectivity.

N-Heterocyclic Carbene-Catalyzed Atroposelective Synthesis of Pyrrolo[3,4-b]pyridines with Configurationally Stable C-N Axial Chirality.

The first atroposelective synthesis of pyrrolo[3,4-b]pyridines catalyzed by N-heterocyclic carbene has been achieved. A wide range of chiral atropisomers of pyrrolo[3,4-b]pyridines were obtained in high yields with excellent enantioselectivities (96-99% enantiomeric excess). The experimental results and density functional theory calculations showed that the C-N axial chirality of the product had high thermal stability.

Enantioselective addition of phenylacetylene to aldehydes catalyzed by polymer-supported titanium(IV) complexes of beta-hydroxy amides.

A series of polymer-supported chiral beta-hydroxy amides and C(2)-symmetric beta-hydroxy amides have been synthesized and successfully used for the enantioselective addition of phenylacetylene to aldehydes. High yields (up to 93%) and enantioselectivities (up to 92% ee) were achieved by using polymer-supported chiral beta-hydroxy amide 4b. The resin 4b is reused four times, giving the product with enantioselectivity 80% ee. Fortunately, it is found that this heterogenous system is suitable not only for aromatic aldehydes but also aliphatic aldehyde.

Sequential Visible-Light and N-Heterocyclic Carbene Catalysis: Stereoselective Synthesis of Tetrahydropyrano[2,3-b]indoles.

An efficiently stereoselective [4 + 2] cycloaddition of 3-alkylenyloxindoles and α-diazoketones through sequential visible-light photoactivation and N-heterocyclic carbene catalysis was achieved. A series of tetrahydropyrano[2,3-b]indoles with an all-carbon quaternary stereocenter were obtained in good yields with excellent diastereo- and enantioselectivities.

Oxidative NHC catalysis: direct activation of ß sp3 carbons of saturated acid chlorides.

The first activation of saturated acid chlorides by oxidative N-heterocyclic carbene catalysis has been successfully utilized to synthesize enantio-enriched spirooxindole lactones and δ-lactones. The reaction involves the transformation of the ß sp3 carbon of saturated acid chlorides into an electrophilic carbon as a key step. The product was obtained in excellent yield and stereoselectivity.

Highly enantioselective synthesis of functionalized azepino[1,2-a]indoles via NHC-catalyzed [3+4] annulation.

The enantioselective [3+4] annulation of 3-formylindol-2-methyl-malonates with 2-bromoenals catalyzed by NHCs is described to afford functionalized azepino[1,2-a]indoles in high yields with excellent enantioselectivities. This method, in which the 3-formyl group in indoles acts as a necessary mediating group, provided cycloaddition products under mild conditions.

AlAr3(THF): highly efficient reagents for cross-couplings with aryl bromides and chlorides catalyzed by the economic palladium complex of PCy3.

Novel and highly efficient cross couplings of aryl bromides and chlorides with AlAr3(THF) (Ar = Ph, 2,4,6-Me3C6H2, 2-naphthyl or 4-Me3SiC6H4) catalyzed by the economic palladium catalyst of PCy3 are reported without the use of a base and under mild reaction conditions at room temperature or temperatures < or = 60 degrees C even for couplings of bulky aryl halides and the Al(2,4,6-Me3C6H2)3(THF) reagent.

Asymmetric Synthesis of Cyclopenta[3,4]pyrroloindolones via N-Heterocyclic Carbene-Catalyzed Michael/Aldol/Lactamization Cascade Reaction.

The N-heterocyclic carbene-catalyzed asymmetric Michael/aldol/lactamization cascade reaction of enals and indole-derived enones for the synthesis of functionalized cyclopenta[3,4]pyrroloindolones with four consecutive stereogenic centers has been achieved. The products were obtained in good yield with high diastereoselectivity and excellent enantioselectivity.

Stereoselective Synthesis of Functionalized Tetrahydro-1H-1,2-diazepines by N-Heterocyclic Carbene-Catalyzed [3 + 4] Annulation.

An efficient N-heterocyclic carbene (NHC)-catalyzed asymmetric [3 + 4] annulation reaction of N-Ts hydrazones with 2-bromoenals has been developed. A series of functionalized tetrahydro-1H-1,2-diazepines with two consecutive stereocenters was obtained using NHCs as the catalyst in good yields with excellent diastereo- and enantioselectivities.

Highly stereoselective synthesis of functionalized pyrrolo[3,2-c]quinolines via N-heterocyclic carbene catalyzed cascade sequence.

An N-heterocyclic carbene-catalyzed stereoselective Michael-Mannich-lactamization cascade reaction of tosyl-protected o-amino aromatic aldimines and 2-bromoenals for the construction of functionalized pyrrolo[3,2-c]quinolines with three consecutive stereocenters was achieved in good yields with excellent diastereo- and enantioselectivities.

N-heterocyclic carbene-catalyzed stereoselective cascade reaction: synthesis of functionalized tetrahydroquinolines.

The first N-heterocyclic carbene-catalyzed stereoselective aza-Michael-Michael-lactonization cascade reaction of 2'-aminophenylenones and 2-bromoenals for the construction of chiral functionalized tetrahydroquinolines with three consecutive stereogenic centers has been achieved in high yields (up to 98%) with excellent diastereo- (>25:1) and enantioselectivities (up to 98.7% ee).

Synergistic chiral ion pair catalysts for asymmetric catalytic synthesis of quaternary α,ß-diamino acids.

The combination of a chiral phosphate anion with a silver ion has been demonstrated as a powerful and synergistic ion pair catalyst for the aza-Mannich reaction. A series of valuable quaternary α,ß-diamino acid derivatives was obtained in high yield, and with excellent diastereo- (up to 25:1 dr) and enantioselectivity (up to 99% ee). The adducts can be smoothly transformed into the corresponding protected chiral quaternary α,ß-diamino acids by a one-pot hydrolysis reaction.

[Cell proliferation inhibited by TIP-6 through autophagy in human hepatoma cell line HepG2 and human normal hepatocyte cell line L02].

AIM: To investigate the effect of 7-(4-methoxyphenyl)-5, 8a-diphenyl-1, 2, 3, 7, 8, 8a-hexahydroimidazo[1, 2-a]pyridine (TIP-6) on cell proliferation in human hepatoma cell line HepG2 and human normal hepatocyte cell line L02. METHODS: Typan blue assay was used to check the effect of TIP-6 on cell proliferation. The changes of cell morphology were observed by the phase contrast microscope. Flow cytometry (FCM) was used to check cell cycle. Autophagy and autophagic cell death were detected after acridine orange (AO) staining under fluorescent microscopy. Apoptosis was analyzed by Annexin V/7-AAD, DAPI staining and DNA ladder. NF-kappaB expression was detected with cellular immunochemistry. RESULTS: Cell proliferation inhibiting effect was appeared when treated with TIP-6 from 60 mumol/L to 200 mumol/L, which was correlated with treated concentrations and time. The proliferation rates were just 12.10% and 18.75% (vs control) under 200 mumol/L 72 h in HepG2 and L02 respectively. Vacuolization were found more and more frequently with the increasing of TIP-6 concentrations and treated time prolonged. FCM results indicated that cells were blocked in G2/M phase, and more sensitive were found in HepG2 than L02. AO staining results indicated that the phenomenon of autophagy and autophagic cell death were occurred and appeared more potent with more TIP-6 and longer time treated. No apoptosis markers were found with Annexin V/7-AAD and DAPI staining, and no DNA ladders were found either, these indicated that TIP-6 didn't induce apoptosis in these cells. NF-kappaB was found increased after treated with TIP-6, and the autophagic vacuole became more and more with the increasing of NF-kappaB protein, but the proliferation rates decreased at the same time. CONCLUSION: TIP-6 inhibited cell proliferation and induced autophagy and autophagic cell death in HepG2 and L02 cells. NF-kappaB activation may be involved in these effects.

Polystyrene-supported N-sulfonylated amino alcohols and their applications to titanium(IV) complexes catalyzed enantioselective diethylzinc additions to aldehydes.

Crosslinked polystyrene-supported resins 4, 7a, and 7b containing N-sulfonylated beta-amino alcohol in 98, 20, and 40% loadings are prepared. Asymmetric diethylzinc additions to benzaldehyde employing titanium complexes of 10 mol % resins 4, 7a, or 7b are examined and the best performed 7a/Ti(O-i-Pr)4 catalytic system applies to various aldehydes to afford desired secondary alcohols in excellent enantioselectivities up to 95% ee. The resin 7a is reused five times, giving the product with enantioselectivities >or=86% ee and an 81% ee is obtained when the resin is used the sixth time. The used resin 7a is refreshed with 1 M HCl and the asymmetric reaction employing the regenerated resin 7a gives the product in 88% ee.

Synthesis of new N-sulfonylated amino alcohols and application to the enantioselective addition of diethylzinc to aldehydes.

A series of N-sulfonylated amino alcohols were prepared and the enantioselective addition of diethylzinc to aldehydes catalyzed by titanium(IV) complexes of those ligands were carried out. Excellent enantioselectivities were obtained for the desired alcohols with enantiomeric excess values up to 94% of R-configuration.

5-Phenyl-1,3,4-thiadiazol-2-yl 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranoside.

The structure of the title compound, C22H24N2O9S2, is described. This compound consists of a sugar ring and a heterocyclic base linked unusually by an S atom. The sugar is in a 4C1 chair conformation and forms dihedral angles of 49.54 (4) and 33.42 (5)degrees with the thiadiazole and phenyl rings, respectively. The S atom occupies an equatorial position of the sugar ring and lies 1.807 (2) A out of the corresponding mean plane.