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Pyrrolocarbazole skeletons are well known to possess a variety of biological activities that might be therapeutically useful in the treatment of cancers. Herein, an acid-catalyzed stereoselective hydroarylation/Diels-Alder cycloaddition/aromatization of ynamide-indoles is described. We newly designed and synthesized a variety of piperazine-fused pyrrolocarbazole derivatives that could be further applied to the synthesis of potent Wee1 inhibitors.

Disclosed herein is a rhodium(III)-catalyzed intramolecular cyclization of ynamides with propargyl esters. A variety of highly functionalized 2,5-dihydropyrroles were obtained in moderate to good yields with high E / Z selectivities. Subsequent oxidation of the products gave valuable pyrrole derivatives. Additionally, scale-up reactions and late-stage derivatizations highlight the potential synthetic utility of this methodology.

UDPG/P2Y 14 R signaling pathway has been considered as a potential therapeutic target for innate immune system diseases. Based on the scaffold hopping strategy, a series of pyrazole analogues were designed and synthesized as novel P2Y 14 R antagonists with improved physicochemical properties, together with potential anti-inflammatory activities. Additionally, we designed and synthesized a fluorescent probe based on highly selective and potent PPTN to study the affinity of synthesized compounds. The optimized compound 16 (1-(4-fluorobenzyl)-5-(4-methylbenzamido)-1 H -pyrazole-3-carboxylic acid, P2Y 14 R IC 50 = 1.93 nM) showed strong binding ability to P2Y 14 R, high selectivity, notably improved solubility, and more favorable pharmacokinetic profiles. Moreover, compound 16 possessed extremely low cytotoxicity and anti-inflammatory effect in vitro . In an acute peritonitis model, compound 16 could effectively reduce the levels of inflammatory factor IL-6, IL-1β, and TNF-α of mice induced by LPS. Compound 16 , with potent in vitro and in vivo efficacy and favorable druggability, can be a promising candidate for further research.

The biochemical elucidation of the early biosynthetic pathways of miharamycins and amipurimycin revealed the roles of several enzymes, which include GMP hydrolase, represented by MihD/ApmD, and hypothetical proteins, MihI/ApmI, unexpectedly exhibiting the dual function of the guanylglucuronic acid assembly and GMP cleavage. In addition, MihE, a carbonyl reductase that functions on the C2 branch of high-carbon sugars, and MihF, a rare guanine O -methyltransferase, were also functionally verified.

Formation of 3-monochloropropanediol (3-MCPD) esters from monostearoyl glycerol (MSG) was investigated under high temperature and low moisture conditions. Different organic and inorganic chlorides, including lindane, KCl, CaCl 2 , NaCl, MgCl 2 , AlCl 3 , CuCl 2 , MnCl 2 , SnCl 2 , ZnCl 2 , and FeCl 3 , were evaluated for their potential to react with MSG to form 3-MCPD and glycidyl esters at 120 and 240 °C using a UPLC-Q-TOF MS analysis. The results indicated that different chlorine compounds differed in their capacity to react with MSG and formed different products including 3-MCPD mono- and diesters, distearoylglycerol, and glycidyl esters. According to electron spin resonance (ESR) and Fourier transform infrared (FT-IR) spectroscopies, free radical mediated formation mechanisms involving either five-membered or six-membered cyclic acyloxonium free radicals (CAFR) from monoacylglycerol (MAG) were proposed. Tandem quadrupole-time-of-flight (Q-TOF) MS and MS/MS analyses confirmed the free radical mechanisms. In addition, the results from the present study showed that 3-MCPD monoester could be degraded upon thermal treatment and suggested a possible catalytic role of Fe 3+ under the experimental conditions.

The adsorption of six symmetrical cationic (dimethylammonium bromide) gemini surfactants with four different partially fluorinated chains at three different surfaces--the air/water, the hydrophilic silica/water, and the hydrophobic (octadecyltricholorosilane (OTS))/water--has been investigated by neutron reflectometry. The corresponding single chain trimethylammonium bromides have also been studied at the two solid surfaces. Four of the geminis with a C(6) spacer and chains with differing amounts of fluorocarbon have identical limiting areas per molecule at the air/water interface (106 ± 5 Å(2)). This is similar to the value for the corresponding hydrocarbon gemini with a C(6) spacer and C(12) side chains, but unlike the hydrocarbon gemini, it is significantly more than twice the area per molecule of the corresponding single chain cationic. In adsorbed aggregates on hydrophilic silica the area per molecule decreases from the air/water value by an average of about 25%, indicating a substantial improvement in the packing of these geminis in the aggregate, which can be attributed to the stronger interaction between the hydrophobic chains in the interior of the aggregates. On the hydrophobic OTS surface the area per molecule in the adsorbed monolayer for three partially fluorinated geminis decreased by about 15% from the air/water value, again indicating much more favorable packing next to the hydrophobic OTS, but for one of the geminis, fC(8)C(6)-C(6)-C(6)fC(8), the change in area was reversed. This reversal is accompanied by a marked thinning of the layer, which is attributed to a shift in the balance between the interactions of the hydrocarbon spacer and fluorocarbon chain fragments and the OTS surface.

We here report our experimental study of the quantum size effect modulated metalation reaction of phthalocyanine (H(2)Pc) by low temperature scanning tunneling microscopy. When iron atoms were deposited onto Pb(111) thin films (2-5 nm thick) precovered by a self-assembled H(2)Pc monolayer, a surface metalation reaction to iron phthalocyanine (FePc) was observed. The amount of the FePc products was found to change prominently whenever the film thickness varies by one atomic layer and exhibits thickness-dependent oscillatory behavior. We show that the oscillation can be well-understood by the quantum size effect in the Pb thin films. The present study gives direct proof for tailoring a surface chemical reaction by quantum confinement.