A novel injectable poly(epsilon-caprolactone)/calcium sulfate system for bone regeneration: synthesis and characterization

A novel poly(epsilon-caprolactone)/calcium sulfate system was prepared and characterized in order to enhance calcium sulfate (gypsum) performance as bone graft substitute overcoming its brittleness and fast resorption rate. A poly(epsilon-caprolactone) (PCL) photo-crosslinkable derivative (PCLf) was synthesized by reaction of a low molecular weight PCL diol with methacryloyl chloride and confirmed by FT-IR and 1H NMR analyses. An injectable and easy mouldable mixture of PCLf and calcium sulfate hemi-hydrate (PCLf/CHS) was obtained. Thermal analyses and solvent extraction proved the occurrence of PCLf photo-crosslinking, even in the presence of CHS, in a time suitable for clinical applications. Swelling studies demonstrated that the encapsulation of the inorganic filler increases network hydrophilicity making it more permeable to water. Scanning electron microscopy, performed on crosslinked PCLf/CHS and on the same material after incubation in a PBS solution, showed the feasibility to obtain, in situ, gypsum entrapped into a degradable polymeric network. In vitro cytotoxicity tests, performed according to ISO 10993-5, proved that the developed system was not cytotoxic supporting its potential use in tissue engineering as a new, injectable, photocurable bone graft material. SEM micrograph of calcium sulfate di-hydrate (gypsum) entrapped in the PCL network.     

SmI2－Mediated Addition Reaction of α－Halomethylsulfones to Carbonyl Compounds. A Convenient Synthesis of β－Hydroxysulfones

Due to the chemoselective dehalogenation by SmI2, the addition of a-halomethylsulfones to carbonyl compounds afforded ,β-hydroxysulfones. Those reactions with α-bromomethylsulfones gave the products in moderate to good yields. The SmI2-mediated addition of gem-dihalomethylsulfones to ketones also afforded α-halo-β-hydroxysulfones in moderate yields.     

Palladium-catalyzed asymmetric alkylation of 2-azaallyl acetates for the synthesis of β-carboxyaspartic acid derivatives

Palladium-catalyzed asymmetric alkylation of 2-azaallyl acetate, N-(diphenylmethylene)acetoxyglycine ester with a sodium salt of malonate ester was successfully carried out. High enantioselectivities were achieved using sodium dimethyl methylmalonate (98%ee) or sodium dimethyl malonate (93%ee) as a nucleophile with t-butyl ester of 2-azaallyl acetate in the presence of (S)-BINAP in acetonitrile.     

Complete (1)H and (13)C NMR spectral assignment of alpha- and beta-adenosine, 2'-deoxyadenosine and their acetate derivatives

(1)H and (13)C NMR chemical shifts of alpha- and beta-anomers of adenosine, 2'-deoxyadenosine and their acetate derivatives were completely and definitely assigned using the concerted application of one- and two-dimensional experiments (gCOSY, gNOESY, gHSQC and gHMBC). The influence of the stereochemistry of the purine base on the NMR data of the hydrogen and carbon atoms of the furanose moiety was estimated.     

Kallisteine A and B, two new coumarins from the roots of Peucedanum paniculatum L, a species endemic to Corsica

From the dichloromethane extract of the roots of Peucedanum paniculatum L., two new coumarins, a species endemic to Corsica, have been isolated. Their structures were elucidated, on the basis of spectroscopic studies, particularly 1D and 2D NMR spectroscopy, as 6-(7'-beta-cyclolavandulyl)-7-hydroxycoumarin 1 and a spirodihydrofurano-coumarin 2 (Kallisteine A and B).     

Molecular modeling of A1 and A2A adenosine receptors: comparison of rhodopsin- and beta2-adrenergic-based homology models through the docking studies

Adenosine receptors (ARs) are members of the superfamily of G protein-coupled receptors. The homology models of adenosine A1 and A2A receptors were constructed. The high-resolution X-ray structure of bovine rhodopsin and crystal structure of beta2-adrenergic receptor were used as templates. The binding sites of the A1 and A2A ARs were constructed by using data obtained from mutagenesis experiments as well as docking simulations of the respective AR antagonsists DPCPX and XAC. To compare rhodopsin- and beta2-adrenergic-based models, the binding mode of A1 (KW-3902, LUF-5437) and A2A (KW-6002, ZM-241385) ARs antagonists were also examined. The differences in the binding ability of both models were noted during the study. The beta2-adrenergic-based A2A AR model was much more capable to stabilize the ligand in the binding site cavity than the corresponding rhodopsin-based A2A AR model, however, such differences were not so clear in case of A1 AR models. It was suggested that for the A1 AR it is possible to use the crystal structure of rhodopsin as a template as well as beta2-adrenergic receptor, but for A2A AR, with the now available beta2-adrenergic receptor X-ray structure, docking studies should be avoided on the rhodopsin-based model. However, taking into account that the beta2AR shares about 31% of the residues with the AR in comparison to 21% in case of bRho, we suggest using beta2-adrenergic-based models for the A1 and A2A ARs for further in silico ligand screening also because of their generally better ability to stabilize ligands inside the binding pocket.     

Preparation of alpha-diazocarbonyl compounds from beta-lapachone derivatives and other 1,2-naphthoquinones: use of the 2D NMR 1H,15N and 1H,13C HMBC techniques in assigning regiochemistry

The assignment of the diazo site in products of the reaction of p-toluenesulfonylhydrazine with beta-lapachone, 3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione, and other 1,2-naphthoquinones in methanol solution at room temperature has been accomplished using 1H,13C HMBC and 1H,15N HMBC NMR experiments. Only one diazo-naphthalenone product was isolated in yields ranging from 50-100% from each reaction. The site of diazo substitution of beta-lapachone and derivatives is the 1-position, in contrast to substitution at the 2-position in 4-MeO-1,2-naphthoquinone. Steric factors, rather than electronic factors, control the reaction site. Along with 2-diazo-1(2H)-naphthalenone, an additional product isolated from the reaction of p-toluenesulfonylhydrazide with 1,2-naphthoquinone was 2-diazo-4-hydroxy-1(2H)-naphthalenone. Confirmation of the formation of 6-diazo-2,2-dimethyl-2,3,4,6-tetrahydro-2H-benzo[h]cromen-5-one, obtained from beta-lapachone, was achieved using single crystal X-ray diffraction.     

A Facile Method for the Epoxidation of Cyclic Enone Catalyzed by tert-BuNH2 with 30% Hydrogen Peroxide as Oxidant

It was found that tert-BuNH_2 is an efficient catalyst for epoxidation of α,β-unsaturated ketones with 30% H_2O_2under mild conditions.For most of the cyclic unsaturated ketones used,moderate to excellent yields (45%—93%)were obtained within 24 h period.     

Fe3O4@ZrO2/SO42‐: A recyclable magnetic heterogeneous nanocatalyst for synthesis of β‐amino carbonyl derivatives and synthesis of benzylamino coumarin derivatives through Mannich reaction

In the present work, we developed an effective protocol for the synthesis of β‐amino carbonyl compounds and synthesis of benzylamino coumarin derivatives through Mannich type reaction in high yields. Fe₃O₄@ZrO₂/SO₄^2‐ was employed as an effective heterogeneous nanocatalyst for the Mannich reaction. This research consists of two sections. In first section, β‐amino carbonyl derivatives were synthesized under solvent‐free condition. In the other section, benzylamino coumarin compounds were synthesized at room temperature. The present approach offers several advantages such as short reaction times, low cost, easy work‐up, mild reaction conditions, high yields and ease of recovery and reusability of the catalyst without significant loss of activity.     

Characterization of the complex formation of 1,6‐anhydro‐β‐maltotriose with potassium using 1H and 39K NMR spectroscopy

The ¹H and ³⁹K longitudinal relaxation times (T₁) and ¹H diffusion coefficients were measured to investigate the complex formation of 1,6‐anhydro‐β‐maltotriose and potassium ions. Although the ¹H‐T₁ values of H3′, H5′, H1″ and H4″ decreased in the presence of potassium ions, ¹H chemical shifts and ¹H diffusion coefficients did not show significant changes. The long‐range coupling constants of ³J_C?H around the glycosyl bonds did not show significant changes either. In the measurements of ³⁹K spectra, the ³⁹K signal obviously broadened and the ³⁹K‐T₁ values decreased in the presence of 1,6‐anhydro‐β‐maltotriose, indicating the complex formation of 1,6‐anhydro‐β‐maltotriose and potassium ions. These results indicate that the conformation and molecular volume were unaffected in the complex formation. Copyright © 2009 John Wiley & Sons, Ltd.     

New approach to the synthesis of 4-amino-2-pyridone and 1-phenyl-1,6-naphthyridinone derivatives based on substituted 3-and 5-formyl-2-pyridones

The reactions of 3-cyano-3(5)-formyl-2-oxo-4-(phenylamino)-1,2-dihydropyridines with CH acids were studied. The previously unknown fused 2-pyridone derivatives containing the 4-aminopyridine fragment were synthesized by the Knoevenagel reaction. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1416-1420, August, 2006.     

Cu(OTf)_2-catalyzed ring-opening of epoxides with anilines:A convenient synthesis of β-amino alcohols

The regioselective ring-opening of epoxides with aniline and p-chlorop niline catalyzed by copper(Ⅱ) triflate provides the corresponding β-amino alcohols in excellent yields.     

Some Novel Dinuclear phenylboronates of biologically potent β‐enaminoesters: Synthesis,Spectroscopic characterization,antimicrobial activity and their antiandrogenic effect

Organoboron derivatives of biologically potent β‐enamino esters of the type [Where R = CH₃(1a), C₂H₅ (1b), C₃H₇(1c) and C (CH₃)₃ (1d)] have been prepared by the reactions of β‐enamino esters and Phenyl boronic acid [PhB (OH)₂] in 1:2 molar ratio in refluxing tetrahydrofuran (THF). All these derivatives have been characterized by physico‐chemical properties, elemental analyses and molecular weight measurements. The structures of these compounds have been proposed on the basis of IR, ¹H, ¹³C, ¹¹B NMR spectral data and GC‐mass spectrometry. Phenyl boronic acid, β‐enamino esters and their respective phenylboronates derivatives have been screened for the antibmicrobial activities against pathogenic bacteria (B. subtilis and E. coli) and fungi (A. niger and P. peniculosum) to access their growth inhibiting potential. In addition to this, antiandrogenic effect of Ligand, L^aH₂ and its boron derivative (1a) has also been tested in male albino rats.     

Ni(OAc)2: a highly efficient catalyst for the synthesis of enaminone and enamino ester derivatives under solvent‐free conditions

Ni(OAc)₂ was found to be an efficient catalyst for the synthesis of β‐enamino ketones or esters from β‐dicarbonyl compounds and amines under solvent‐free conditions. The reusability of the catalyst was successfully examined without noticeable loss of its catalytic activity. Copyright © 2010 John Wiley & Sons, Ltd.     

首次合成来源于鼠李属植物中的两个新颖的蒽环鼠李糖苷，2’, 3’-Di-O-acetylfrangulin A 和 Prinoidin

首次全合成来源于鼠李属植物中的两个天然产物2’, 3’-di-O-acetylfrangulin A (1) 和 prinoidin (2),它们对KB细胞表现出较好的细胞毒活性。通过1H NMR, 13C NMR, 1H-1H COSY, HMQC 和 HMBC确证了两个化合物的结构。     

Asymmetric Henry reaction catalysed by L‐proline derivatives in the presence of Cu(OAc)2: isolation and characterization of an in situ formed Cu(II) complex

Synthesis of asymmetric β‐nitroalcohols by the Henry reaction is one of the most exploited carbon–carbon bond‐forming reactions owing to the versatility of both functional groups for synthetic manipulation by functional group interconversion. Here we report synthesis of a series of proline‐derived compounds to study their catalytic activities for asymmetric Henry reaction in the presence of Cu(OAc)₂.H₂O. The proline derivative, 2‐((E)‐(((S)‐1‐benzylpyrrolidinyl)diphenylmethylimino)methyl)phenol 1 showed optimum catalytic activity. The catalytic species Cu(II)–1 complex, formed in situ, was isolated and characterized by various spectroscopic techniques and X‐ray crystallography to show a cis‐N₂O₂ coordination geometry. Asymmetric β‐nitroalcohols were achieved without the use of added base, unlike most of the reported protocols. Copyright © 2014 John Wiley & Sons, Ltd.     

羟丙基-β-环糊精磁性复合微粒的合成及作为阿霉素载体的体外释药研究

羟丙基-β-环糊精因具有内部疏水和外部亲水锥形圆筒空腔结构和良好的生物相容性在磁性药物载体方面有潜在应用价值。本研究将羟丙基-β-环糊精修饰在超顺磁性纳米四氧化三铁粒子表面制备磁性复合微粒,用红外光谱,透射电镜,振动磁强计,电感耦合等离子发射等方法对该复合微粒进行了表征,并将其用于抗肿瘤药物阿霉素的体外载药与释药实验研究。结果表明该复合微粒的粒径大小在10-20nm,饱和磁化强度59.9 emu/g,铁含量55.4%。对阿霉素的载药量为87.8 μg/mg。体外释药结果显示载药复合粒子在PBS中1天,4天,10天的累积释药量分别为35.5%, 49.3%, 76.5%,表明该载体具有一定的药物缓释功能。由此可知,羟丙基-β-环糊精磁性复合微粒可作为磁性靶向给药系统的有效载体。     

A novel synthetic route to 2-alkylpropane-1,3-sultones and its application to the synthesis of 2-alkyl derivatives of tramiprosate

A practical synthetic route to various 2-alkylpropane-1,3-sultones, the key intermediates for the preparation of 2-substituted homotaurines as analogs of tramiprosate, was developed.     

Pyrazinium Di(hydrogen sulfate) as a Novel,Highly Efficient and Homogeneous Catalyst for the Condensation of Enolizable Ketones with Aldehydes,Acetonitrile and Acetyl Chloride

A highly efficient protocol for the synthesis of β‐acetamido ketone or ester derivatives in the presence of pyrazinium di(hydrogen sulfate) {Py(OSO₃H)₂} as a novel, green and homogeneous solid acid catalyst at room temperature is described. One‐pot multi‐component condensation of enolizable ketones or alkyl acetoacetates with aldehydes, acetonitrile and acetyl chloride affords the title compounds in high to excellent yields and in relatively short reaction times. In this work, the efficiency of our recently reported solid acid catalyst, saccharin sulfonic acid (Sa‐SO₃H), in the synthesis of β‐acetamido ketones/esters is also studied. Moreover, in this research, some new β‐acetamido ketones and esters (i.e. one complex structure) are prepared.     

Catecholborane Reductive Cleavage of Allyl and Propargyl Acetals and Ketals: A Simple Route to Allyl and Prop-2-ynyl Ethers

the chemoselective conversion of allyl and prop-2-ynyl acetals as well as ketals by reductive cleavage with catecholborane into the corresponding allyl and prop-2-ynyl ethers is described.