Blockade of TGF-β/Smad signaling by the small compound HPH-15 ameliorates experimental skin fibrosis.

Background: Transforming growth factor-β (TGF-β)/Smad signaling is well known to play a critical role in the pathogenesis of systemic sclerosis (SSc). We previously developed an artificial molecule, the histidine-pyridine-histidine ligand derivative HPH-15, which may have an antifibrotic effect. The purpose of the present study was to clarify the effects of this drug in human skin fibroblasts and in a preclinical model of SSc.

A novel inhibitor of farnesyltransferase with a zinc site recognition moiety and a farnesyl group.

Protein prenylation such as farnesylation and geranylgeranylation is associated with various diseases. Thus, many inhibitors of prenyltransferase have been developed. We report novel inhibitors of farnesyltransferase with a zinc-site recognition moiety and a farnesyl/dodecyl group.

Efficient Decarbonylation of Furfural to Furan Catalyzed by Zirconia-Supported Palladium Clusters with Low Atomicity.

Decarbonylation of furfural to furan was efficiently catalyzed by ZrO -supported Pd clusters in the liquid phase under a N atmosphere without additives. Although Pd/C and Pd/Al O have frequently been used for decarbonylation, Pd/ZrO exhibited superior catalytic performance compared with these conventional catalysts. Transmission electron microscopy and X-ray absorption fine structure measurements revealed that the size of the Pd particles decreased with an increase in the specific surface area of ZrO .

Direct C-H arene homocoupling over gold nanoparticles supported on metal oxides.

The direct CH/CH bond coupling of dimethyl phthalate was performed successfully over supported gold nanoparticle catalysts. Gold on reducible metal oxides, such as Co3 O4 , and on inert oxides that have an oxygen-releasing capacity, such as ZrO2 , showed the highest catalytic activity for the production of biphenyl tetracarboxylate using O2 as the sole oxidant. Supported Pd(OH)2 also catalyzed the reaction, but the catalytic activity was inferior to that of gold.

Homogeneous Pd-catalyzed transformation of terminal alkenes into primary allylic alcohols and derivatives.

Synthesis of primary alcohols from terminal alkenes is an important process in both bulk and fine chemical syntheses. Herein, a homogeneous Pd-complex-catalyzed transformation of terminal alkenes into primary allylic alcohols, by using 5 mol % [Pd(PPh3)4] as a catalyst, and H2O, CO2, and quinone derivatives as reagents, is reported. When alcohols were used instead of H2O, allylic ethers were obtained.

Hydrolytic enantioselective protonation of cyclic dienyl esters and a β-diketone with chiral phase-transfer catalysts.

Hydrolytic enantioselective protonation of dienyl esters and a β-diketone catalyzed by phase-transfer catalysts are described. The latter reaction is the first example of an enantio-convergent retro-Claisen condensation. Corresponding various optically active α,β-unsaturated ketones having tertiary chiral centers adjacent to carbonyl groups were obtained in good to excellent yields and enantiomeric ratios (83-99%, up to 97.

Synthesis and Preliminary Evaluation of Duocarmycin Analogues Incorporating the 1,2,11,11a-Tetrahydrocyclopropa[c]naphtho[2,3-e]indol-4-one (CNI) and 1,2,11,11a-Tetrahydrocyclopropa[c]naphtho[1,2-e]indol-4-one (iso-CNI) Alkylation Subunits.

Efficient syntheses and a preliminary evaluation of 1,2,11,11a-tetrahydrocyclopropa[c]-naphtho[2,3-e]indole (CNI) and 1,2,11,11a-tetrahydrocyclopropa[c]naphtho[1,2-e]indole (iso-CNI), and their derivatives containing an anthracene and phenanthrene variant of the CC-1065 or duocarmycin alkylation subunit are detailed.

One-pot synthesis of indoles and aniline derivatives from nitroarenes under hydrogenation condition with supported gold nanoparticles.

One-pot sequences of hydrogenation/hydroamination to form indoles from (2-nitroaryl)alkynes and hydrogenation/reductive amination to form aniline derivatives from nitroarenes and aldehydes were catalyzed by Au nanoparticles supported on Fe(2)O(3). Nitro group selective hydrogenations and successive reactions were efficiently catalyzed under the conditions.

Enhancement of reaction efficiency by functionalized alcohols on gold(I)-catalyzed intermolecular hydroalkoxylation of unactivated olefins.

Intermolecular hydroalkoxylation of unactivated olefins catalyzed by the combination of gold(I) and electron deficient phosphine ligands has been developed. Although pairings of unactivated olefins and common aliphatic alcohols gave unsatisfactory results in gold catalyzed hydroalkoxylations, the use of alcohol substrates bearing coordination functionalities such as halogen or alkoxy groups showed great improvement of reactivity.

Antiviral activities against herpes simplex virus type 1 by HPH derivatives and their structure-activity relationships.

The compound named Histidine-pyridine-histidine (HPH) is an oxygen-activating ligand derived from the structure of bleomycin. We synthesized HPH derivatives, namely HPH-1 to -8, and investigated their antiviral activities against herpes simplex virus type 1. HPH-8 showed potent antiviral activity with an EC50 of 15 microM, and relatively high cytotoxicity with a CC50 of 37 microM.

Two novel 1,2,4,5-tetrazines that participate in inverse electron demand Diels-Alder reactions with an unexpected regioselectivity.

[reaction: see text] Two new unsymmetrical 1,2,4,5-tetrazines, 3-methylsulfinyl-6-methylthio-1,2,4,5-tetrazine (4) and 3-(benzyloxycarbonyl)amino-6-methylsulfinyl-1,2,4,5-tetrazine (5), were prepared, and the scope of their participation in intermolecular inverse electron demand Diels-Alder reactions was defined. As anticipated, sulfoxides 4 and 5 (4 > 5) display a reactivity that is substantially greater than that of their corresponding sulfides (2 and 3), being derived from their enhanced electron-deficient character and resulting in a wider range of potential dienophile choices or the use of milder reaction conditions. The cycloaddition reactions were expectedly regioselective, typically producing a single cycloadduct, ensuring their synthetic utility, but both were found to proceed with a regioselectivity opposite what would be anticipated and complementary to that observed with 2 and 3.

Total synthesis of ningalin D.

A concise (nine-step) and effective (19% overall yield) total synthesis of ningalin D (1a) is disclosed and is based on a key 1,2,4,5-tetrazine --> 1,2-diazine --> pyrrole Diels-Alder strategy to assemble a fully substituted pyrrole core central to its structure. Additional highlights of the synthesis include a double Dieckmann condensation to introduce the C and D aryl rings enlisting substituents judiciously placed on the dienophile and intrinsic to the widely used tetrazine 2, a highly effective Suzuki coupling of the resulting C and D phenol triflates for introduction of the sterically demanding F and G aryl rings, and an unusually effective formal oxidative decarboxylation reaction cascade initiated by a Curtius rearrangement to directly provide the biphenylene quinone methide found imbedded in the structure of ningalin D. The cytotoxic and multidrug resistance (MDR) reversal activity of ningalin D, its derivatives, and the key synthetic intermediates are detailed.

A novel metal-chelating inhibitor of protein farnesyltransferase.

A novel metal chelator comprising a 4-(naphthalen-1-yl)pyridine and 2-aminoethanethiol was synthesized. This showed inhibitory activity against human protein farnesyltransferase with IC(50) 1.9 microM, induced morphological change in K-ras-NRK cells at 0.