Synthesis and structural elucidation of novel camphor-derived thioureas

Nine novel (+)-camphor-derived thioureas have been prepared. 3-((Dimethylamino)methylene)camphor (2) served as the common precursor for the preparation of both, 2-thiourea 15-20 and 3-thiourea functionalized camphor derivatives 6, 7/7', respectively. Starting from 2, the latter were prepared in two or three steps whereas the former in five steps, respectively. Configuration of all novel compounds has been meticulously determined using NMR techniques and/or single crystal X-ray crystallography.     

Synthesis of 2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)-3-((dimethylamino)methyl)camphor organocatalysts

In a stereo-divergent synthesis, three novel camphor-derived bifunctional thiourea organocatalysts 7-9 have been prepared in five steps starting from (+)-camphor. In addition, borneol-derived bifunctional thiourea organocatalysts 19/19' have been prepared in three steps from (1S)-(+)-camphorquinone. Novel organocatalysts 7-9, 19/19' have been evaluated in a model reaction of Michael addition of dimethyl malonate to trans-β-nitrostyrene with low to moderate enantioselectivities (20%-60% ee). Configuration of all novel compounds has been meticulously determined using nuclear magnetic resonance (NMR) techniques.     

Synthesis of Novel Camphor‐Derived Bifunctional Thiourea Organocatalysts

Synthesis and catalyst performance of 2,3‐ (types B and C ) and 2,8‐disubstituted (type D ) thiourea bifunctional organocatalysts was attempted. The synthesis of catalyst of type B has, so far, not been realized, while catalysts of type C , i.e., the 2,3‐exo‐ and the 2‐endo‐3‐exo‐thiourea catalysts, were prepared in six steps starting from (+)‐camphor. The catalysts of type D were prepared from (+)‐camphor in eight steps. All the potential catalysts as well as most of the intermediate products were carefully structurally characterized. The thiourea bifunctional organocatalysts were tested in a model reaction of Michael addition of dimethyl malonate to trans‐β‐nitrostyrene. Chirality 27:39–52, 2015. © 2014 Wiley Periodicals, Inc.     

Synthesis, characterization and electrocatalysis of diiron propanediselenolate derivatives as the active site models of [FeFe]-hydrogenases

As an extension of our study on the H-cluster model compounds, a series of diiron propanediselenolate (PDS)-type models have been successfully synthesized. Reaction of diselenol HSe(CH₂)₃SeH with Fe₃(CO)₁₂ in THF (tetrahydrofuran) at reflux gave the parent model compound [μ-Se(CH₂)₃Se-μ]Fe₂(CO)₆ (1) in 48% yield. Further reaction of 1 with PPh₃ or PPh₂H in the presence of Me₃NO in MeCN at room temperature afforded the phosphine-monosubstituted model compounds [μ-Se(CH₂)₃Se-μ]Fe₂(CO)₅(L) (2, L = PPh₃; 3, L = PPh₂H) in 76% and 68% yields, respectively. Similarly, the N-heterocyclic carbene I_Mes-monosubstituted model compound [μ-Se(CH₂)₃Se-μ]Fe₂(CO)₅(I_Mes) (4) could be prepared in 46% yield by reaction of imidazolium salt I_Mes · HCl with n-BuLi followed by treatment of the resulting I_Mes ligand with 1 in THF at room temperature. Compounds 1-4 were fully characterized by elemental analysis and various spectroscopic methods. While the structures of 1-4 were further confirmed by X-ray crystallography, the comparative study of 1 and its analog [μ-S(CH₂)₃S-μ]Fe₂(CO)₆ demonstrates that 1 is a better catalyst for TsOH proton reduction to hydrogen under electrochemical conditions.     

Synthesis,Structural Characterization,and Chiroptical Studies of Bidentate Salen‐Type Lanthanide (III) Complexes

The salen‐type ligand prepared with (R,R) diphenylethan‐1,2‐diamine and salicylaldehyde provides stable and inert complexes KLnL₂ upon simple reaction with lanthanide halides or pseudohalides LnX₃ (Ln = Tb³⁺‐Lu³⁺; X = Cl^? or TfO^?) of its potassium salt. All the complexes were completely characterized through nuclear magnetic resonance (NMR), electronic circular dichroism (ECD) in the UV and some (Er³⁺, Tm³⁺, Yb³⁺) also with Near‐IR ECD (NIR‐ECD) and luminescence (Tb³⁺, Tm³⁺). Careful analysis of the NMR shifts demonstrated that the complexes are isostructural in solution and afforded an accurate geometry. This was further confirmed by means of Density Functional Theory (DFT) optimization of the Lu³⁺ complex, and by comparing the ligand‐centered experimental and time‐dependent TD‐DFT computed UV‐ECD spectra. As final validation, we used the NIR‐ECD spectrum of the Yb³⁺ derivative calculated by means of Richardson's equations. The excellent match between calculated and experimental ECD spectra confirm the quality of the NMR structure.  Chirality 27:857–863, 2015. © 2015 Wiley Periodicals, Inc.     

铜离子-半胱氨酸配合物的合成及表征

研究了铜离子-半胱氨酸配合物的合成方法,探讨了合成工艺的主要影响因素,确定了原料配比,pH值,最佳反应时间及温度,采用X射线衍射光谱对配合物进行表征,结果表明铜离子能与半胱氨酸形成配合物。     

Synthesis of Schiff Bases and Secondary Amines with Indane Skeleton; Evaluation of Their Antioxidant,Antibiotic, and Antifungal Activities

In this study, Schiff bases were synthesized by utilizing the reaction of 4- and 5-aminoindane with substituted benzaldehydes. After the reduction of isolated Schiff bases with NaBH₄, the corresponding secondary amine derivatives were obtained. The structures of all synthesized molecules were confirmed by ¹H-NMR, ¹³C-NMR, FT-IR, and ESI-MS. Antioxidant activities of all synthesized molecules were investigated by DPPH method, and IC₅₀ values were calculated. In addition, antibacterial activities of targets were investigated by the well diffusion method, and then MIC99 values were calculated. While only four of the sixteen synthesized molecules showed a high level of antioxidant activity, all of the molecules exhibited biological activity against Gram-positive and Gram-negative bacteria to varying degrees. In addition, all the synthesized molecules showed high antifungal activity. In antioxidant capacity studies, the IC₅₀ values of 2-(((2,3-dihydro-1H-inden-5-yl)amino)methyl)-6-methoxyphenol ( 4 d ) and 2-(((2,3-dihydro-1H-inden-4-yl)amino)methyl)-6-methoxyphenol ( 7 d ) were determined to be 18.1 μg and 35.1 μg, respectively, and these values are much stronger than BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole) used as positive controls. The fact that targets have the same core structure with different substituents has revealed a good structure-activity relationship.     

Synthesis of Indolyldiketopiperazines with NBS

Two series of indolyldiketopiperazines were synthesized starting from methyl 1‐substituted‐1,2,3,4‐tetrahydro‐β‐carboline‐3‐carboxylate hydrochlorides via N‐bromo‐succinimide (NBS) as an important reagent. All eight compounds were characterized by nuclear magnetic resonance (NMR) and elemental analysis. Furthermore, the mechanisms of NBS‐reacted rearrangements are also discussed. Chirality 26:790–792, 2014. © 2014 Wiley Periodicals, Inc.     

PDZ结构域的结构特点及其识别特异性配体的机制

PDZ结构域作为介导蛋白质之间相互作用的重要结构域之一,参与到细胞内运输、离子通道、以及各种信号传导通路等多种生物学过程.PDZ结构域是由80~100个氨基酸组成的小的球状结构域,对某些多PDZ结构域蛋白来说,需要一前一后形成串联体才能正确折叠.另外,PDZ结构域相互之间也可以形成同源或异源二聚体.这些PDZ结构域的突出特点是能特异性地识别配体靶蛋白C末端短的氨基酸序列,但有些也能识别靶蛋白的内部β发夹结构.而一些支架蛋白的PDZ结构域与细胞膜上脂类的相互作用则增加了其与膜的亲和性.本文简要概括了PDZ结构域的结构特点及其对配体的各种特异性识别的机制,从而为研究各种PDZ蛋白的功能提供了结构基础.     

Testing the Effects of Biogenic Amines and Alternative Topical Solvent Types on the Behavioral Repertoire of Two Web‐Building Spiders

Investigating the proximate mechanism underlying behavior has long been a primary goal of ethologists. With the recent focus on behavioral correlations (e.g., behavioral syndromes), a fundamental question arises regarding what mechanisms may drive positive relationships between functionally distinct behaviors. Understanding these mechanisms can inform critical questions, such as why distinct behaviors are often correlated, and can also lend insights into how behavioral similarities are conserved across species. Arthropods provide an idea system to study these questions as the biogenic amines, such as octopamine and serotonin, have long been known to mediate a large number of behaviors such as aggression, dominance, escape behavior, and others. Behaviorists have several ways in which they can manipulate these biogenic amines in vivo, including injection, feeding, and topical application. Topical application is potentially an optimal method for manipulating amine concentrations, given that it is minimally invasive and relatively precise. Here, we investigate the role of biogenic amines, octopamine, and serotonin, in mediating a range of similar and often correlated behaviors in two distantly related species of spiders, the western black widow, Latrodectus hesperus, and the funnel‐web spider, Agelenopsis pennsylvanica. Additionally, we investigate the behavioral effects associated with three commonly used carrier solvents: dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and acetone. We demonstrate that biogenic amines are involved both in mediating several behaviors, and also potentially the links between different behaviors. We also show that the same behaviors in different species are not affected by biogenic amines in the same manner, suggesting differences in the underlying neurophysiological mechanisms governing behavior. Furthermore, we discovered large and pervasive effects associated with both carrier solvents, thus calling into question the potential usefulness and interpretability of topical application methods in behavioral research.     

Amino Acids and Biogenic Amines in Cerebrospinal Fluid of Patients with Parkinson's Disease

To study changes in amino acid metabolism and biogenic amines in Parkinson's disease, we set up a prospective study and measured biogenic amines, their main metabolites, and 22 different amino acids, in cerebrospinal fluid of Parkinson's disease patients (n = 24) and age-matched controls (n = 30). A trend toward higher dopamine levels in Parkinson's disease patients was interpreted as an effect of treatment with levodopa and/or selegiline. Significantly lower concentrations of the dopamine metabolite 3,4-dihydroxyphenylacetic acid in the Parkinson's disease group might reflect dopaminergic cell loss. Our results revealed decreased serotonin catabolism that was interpreted as an effect of treatment with selegiline. Whereas all amino acid levels were unchanged, taurine was significantly lower in Parkinson's disease patients. Studies showed that taurine exerts a trophic action on the central nervous system. In this view, decreased taurine in a neurodegenerative disorder as Parkinson's disease deserves attention.     

Amines for detection of dopamine by generation of hydrogen peroxide and peroxyoxalate chemiluminescence

A range of nitrogen-containing compounds (alkyl amines, piperazines, cyclohexylamines and nitrogen heterocyclics) were investigated for generation of hydrogen peroxide from dopamine and detection by peroxyoxalate chemiluminescence. Imidazole, ethyleneurea and allantoin among the nitrogen heterocyclic compounds tested generated hydrogen peroxide from dopamine following incubation at 60°C, pH 9.5–10.5, for 0–30 min. Imidazole was the most effective for generation of hydrogen peroxide, but imidazole derivatives with a primary amine side chain (histamine) or thiol (ethylenethiourea) were not effective. The presence of a ketone group (ethyleneurea, allantoin) did not hinder the reaction. Under optimal conditions (30 min incubation, 50 mmol/L imidazole) 10.5 nmol of dopamine could be detected. The cyclohexylamines tested produced low amounts of hydrogen peroxide (0.09–2.74% of light intensity with imidazole), and the piperazines and the alkyl amines tested produced no detectable hydrogen peroxide. Imidazole reacts with the phenolic groups of dopamine in a different manner from monoamine oxidase, and a reagent containing imidazole, ethyleneurea or allantoin was useful for non-enzymatic detection of dopamine by peroxyoxalate chemiluminescence.© John Wiley & Sons, Ltd.     

Synthesis of new pryridyl alcohols and their use as catalysts in the asymmetric addition of diethylzinc to aldehydes.

Optically active new pyridyl alcohols 1-4, which can be easily synthesized by the reaction of (+)-camphor or (-)-menthone with lithiated pyridine derivatives, were applied as chiral ligands in the asymmetric addition of diethylzinc to aldehydes. Good yields with up to 94.0% enantiomeric excesses were observed in these reactions.     

Development of Novel Imaging Fluorescent Agents Bearing Anti-Inflammatory Drugs: Synthesis,Structural Characterization and Evaluation of Biological Activity

Russian Journal of Bioorganic Chemistry - A new series of 5,6-benzocoumarin derivatives carrying anti-inflammatory drugs were synthesized via alkylamide spacers, the target to develop novel imaging...     

Acetylcholinesterase Inhibitory Activity of Modified Lupane,Oleanane, and Ursane A-seco-Triterpenoids

A series of new lupane, ursane, and oleanane type triterpenic A-seco-derivatives containing bromo-, azido-, alkyne-, 1H-tetrazol-5-yl-, 5-methyloxazol-2-yl-, N-(4-(4-methylpiperazin-1-yl)but-2-yn-1-yl), and a carbonyl group at C2, C24, C28, C30 positions has been synthesized. The bioactivity was evaluated by Ellman's method, and the results showed that most of the compounds displayed moderate acetylcholinesterase inhibitory activities in vitro. Among them, A-seco-derivatives of 28-oxo-allobetuline and betulinic acid with bromo- and azido-groups exhibited the most potent inhibitory activity against AChE. Extra experiments showed methyl 2-cyano-3,4-seco-dibromo- and 2-cyano-3,4-seco-diazido-derivatives of betulinic acid as mixed-type inhibitors, with Ki values as low as K_i=0.18 μM and K_i=0.21 μM, respectively.     

Design,Synthesis, Structural and Functional Characterization of Novel Melanocortin Agonists Based on the Cyclotide Kalata B1

Obesity is an increasingly important global health problem that lacks current treatment options. The melanocortin receptor 4 (MC4R) is a target for obesity therapies because its activation triggers appetite suppression and increases energy expenditure. Cyclotides have been suggested as scaffolds for the insertion and stabilization of pharmaceutically active peptides. In this study, we explored the development of appetite-reducing peptides by synthesizing MC4R agonists based on the insertion of the His-Phe-Arg-Trp sequence into the cyclotide kalata B1. The ability of the analogues to fold similarly to kalata B1 but display MC4R activity were investigated. Four peptides were synthesized using t-butoxycarbonyl peptide chemistry with a C-terminal thioester to facilitate backbone cyclization. The structures of the peptides were found to be similar to kalata B1, evaluated by Hα NMR chemical shifts. KB1(GHFRWG;23–28) had a K_i of 29 nm at the MC4R and was 107 or 314 times more selective over this receptor than MC1R or MC5R, respectively, and had no detectable binding to MC3R. The peptide had higher affinity for the MC4R than the endogenous agonist, α-melanocyte stimulation hormone, but it was less potent at the MC4R, with an EC₅₀ of 580 nm for activation of the MC4R. In conclusion, we synthesized melanocortin analogues of kalata B1 that preserve the structural scaffold and display receptor binding and functional activity. KB1(GHFRWG;23–28) is potent and selective for the MC4R. This compound validates the use of cyclotides as scaffolds and has the potential to be a new lead for the treatment of obesity.     

Effects of Seasoning and Heating Device on Mutagenicity and Heterocyclic Amines in Cooked Beef

Pan-roasted beef showed a lower mutagenicity after various degrees of cooking than charcoaled one. The high mutagenicity of charcoaled beef was due to the formation of more heterocyclic amines, especially AαC (2-amino-9 H-pyrido- [2,3-b]indole) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) because of rapid and direct heating on the surface of the meat at a high temperature. Seasoning decreased mutagenicity of pan-roasted beef except the very well done sample with unchanged heterocyclic amine contents, but increased mutagenicity of charcoaled beef with decreased levels of AαC and PhIP, probably due to the change of heterocyclic amine precursors or alternatively to the occurrence of other mutagens.     

Characterization and comparison of adipose tissue‐derived cells from human subcutaneous and omental adipose tissues

Different fat depots contribute differently to disease and function. These differences may be due to the regional variation in cell types and inherent properties of fat cell progenitors. To address the differences of cell types in the adipose tissue from different depots, the phenotypes of freshly isolated adipose tissue‐derived cells (ATDCs) from subcutaneous (SC) and omental (OM) adipose tissues were compared using flow cytometry. Our results showed that CD31^?CD34⁺CD45^?CD90^‐CD105^?CD146⁺ population, containing vascular smooth muscle cells and pericytes, was specifically defined in the SC adipose tissue while no such population was observed in OM adipose tissue. On the other hand, CD31^?CD34⁺CD45^?CD90^?CD105^?CD146^? population, which is an undefined cell population, were found solely in OM adipose tissue. Overall, the SC adipose tissue contained more ATDCs than OM adipose tissue, while OM adipose tissue contained more blood‐derived cells. Regarding to the inherent properties of fat cell progenitors from the two depots, adipose‐derived stem cells (ADSCs) from SC had higher capacity to differentiate into both adipogenic and osteogenic lineages than those from OM, regardless of that the proliferation rates of ADSCs from both depots were similar. The higher differentiation capacity of ADSCs from SC adipose tissue suggests that SC tissue is more suitable cell source for regenerative medicine than OM adipose tissue. Copyright © 2009 John Wiley & Sons, Ltd.