Amino Alcohol Groups Research Articles

Crystal structure of bis-{μ-2-[bis-(2-hy-droxy-eth-yl)amino]-ethano-lato}bis-(μ-3,5-di-methyl-pyrazolato)tricopper(II) dibromide sesquihydrate.

In the title bicyclic trinuclear pyrazolate amino-alcohol complex, [Cu3(C5H7N2)2(C6H14NO3)2]Br2·1.5H2O, the central Cu atom lies on a center of symmetry and is involved in the formation of two five-membered rings. It has a coordination number of 4, is in a distorted tetra-hedral environment and is connected by the bridging oxygen atoms of the deprotonated OH groups of different amino-alcohol groups, and by the N atoms of deprotonated di-methyl-pyrazole ligands. The peripheral Cu atom is in a trigonal-bipyramidal coordination environment formed by the nitro-gen atom of the deprotonated bridging di-methyl-pyrazole unit, the bridging oxygen atom of the deprotonated OH group, two oxygen atoms of the protonated hy-droxy groups and the nitro-gen atom of tri-ethano-lamine. One of the C atoms and the Br- anion were found to be disordered over two positions with occupancy factors of 0.808 (9):0.192 (9) and 0.922 (3):0.078 (3), respectively.

Catalytic Lewis and Brønsted acid syn-diastereoselective benzylic substitutions of α-hydroxy-β-nitro- and α-hydroxy-β-azido-alkyl arenes

A series of alkyl and alkenyl p-methoxy arenes containing α,β-disubstituted diamino and amino alcohol groups were synthesized from β-nitro and β-azido benzylic alcohols in the presence of AuCl3 as catalyst. The formation of predominantly syn-disubstituted products were rationalized on the basis of mechanistic considerations and transition state models relying on A1,3-allylic strain. The products could have utility in the design of medicinally relevant compounds and as chiral ligands for asymmetric catalysis. A new synthesis of (+)-sertraline (Zoloft) was achieved.

Synthesis and Structure of Tin and Germanium Complexes as Precursors Containing Alkoxyaminoalkoxide Ligands for Thin Film Transistors

This paper describes the preparation of four novel Sn and Ge complexes containing alkoxyaminoalkoxide type ligands {L1H = 1‐[methoxy(methyl)amino]‐2‐methylpropan‐2‐ol; L2H = 1‐[methoxy(methyl)amino]‐2‐methylbutan‐2‐ol} for potential use as precursors for thin film transistors. All compounds were prepared at room temperature by stirring a solution containing Sn(btsa)2 [btsa = bis(trimethylsilyl)amide] or Ge(btsa)2 with two equivalents of L1H or L2H to form Sn(L1)2 (1), Sn(L2)2 (2), Ge(L1)2 (3) and Ge(L2)2 (4). All of the complexes were characterized by NMR and FTIR spectroscopy as well as elemental and thermogravimetric analyses. When the more symmetric and compact ligand L1H was applied, solid products 1 and 3 were generated and their structures were studied using X‐ray diffraction. Applying the strategy of ligand design at the molecular level, the symmetric ligand was changed to an asymmetric one, replacing one of the two neighboring methyl groups of the amino alcohol group with an ethyl group, and forming liquid complexes 2 and 4 for both metals.

Self-assembling water-soluble polymethacrylate-MTX conjugates: The significance of macromolecules architecture on drug conjugation efficiency, the final shape of particles, and drug release.

Water-soluble polymer-methotrexate (MTX) conjugates were obtained via efficient carbodiimide-mediated amidation (E = 17-100%). Binding abilities between water-soluble V-shaped or star-shaped copolymers and MTX were studied by isothermal titration calorimetry spectroscopic (UV-vis, NMR) and microscopic (scanning electron microscopy and transmission electron microscopy) techniques. The efficiency of the amidation reaction has depended on the amount of pendant amino alcohol groups and zeta potential (ZP) values of polymeric carries. The sizes of aggregates formed by polymer-drug conjugates in water increased with the number of copolymer arms (202-774 nm at 37°C). Moreover, the conjugates with the high amount of bounded MTX molecules (nMTX > 78) exhibited negative ZP values. The drug release experiments revealed that the amount of the released MTX depends on pH and can be controlled via shape, topology, and composition of polymeric carrier. Preliminary cytotoxicity studies of V-shaped-MTX conjugate on human immortalized nontumorigenic keratinocyte (HaCaT) cells indicated cytocompatibility of the compound in a wide range of concentrations. The results of our studies have shown that physicochemical and drug release properties of obtained polymer-MTX prodrugs can be tailored via the structure and the topology of the polymeric carrier. Thus conjugates might find the application in a different type of treatment (cancer or psoriasis therapy) and administration (intravenous, dermal, or pulmonary). © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2476-2487, 2019.

A Colorimetric Probe for the Selective Detection of Norepinephrine Based on a Double Molecular Recognition with Functionalized Gold Nanoparticles

A simple colorimetric probe for the selective and sensitive detection of neurotransmitter norepinephrine (NE), an important biomarker in the detection of tumors such as pheochromocytoma and paraganglioma, is described. The sensing strategy is based on the use of spherical gold nanoparticles functionalized with benzaldehyde and boronic acid-terminated moieties. A double molecular recognition involving on one hand the aromatic aldehyde and the aminoalcohol group of NE, and on the other hand the boronic acid and the catechol moiety of the neurotransmitter, results in analyte triggered aggregation of the gold nanoparticles, leading to a bathochromic shift of the SPR band in the UV–vis spectrum of the probe and a clear change in the color of the solution from red to blue. Probe P1 shows a remarkable selectivity toward NE versus other catecholamine neurotransmitters (dopamine and epinephrine) and selected biomolecules (5-HIAA, l-Tyr, glucose, uric acid, Lys and glutamic acid). Moreover, a linear response to NE ...

Triazin bazlı kiral floresans bileşiklerin sentezi ve enantiyomerik tanınma çalışmaları

In this study novel fluorescence active, two triazine based thiazole derivatives, (2R,2'R)-2,4,6-triamine-N2-[2-(4-benzothiazolyl)phenyl]-N4,N6-[di(butan-1-ol)]-1,3,5-triazine and (1S,1'S,2R,2'R)-2,4,6-triamine-N2-[2-(4-benzothiazolyl)phenyl]-N4,N6-[di(1,2-diphenylethanol)]-1,3,5-triazine with chiral aminoalcohol groups were synthesized conveniently. Their enantiomeric recognition abilities toward the enantiomers of carboxylic acids such as mandelic acid and 2-chloromandelic acid were examined in DMSO/H2O (30:70) system using fluorescence spectroscopy. It was observed that DMSO solutions of chiral selectors showed no fluorescence emission while the emission increased 38 and 43 fold in 95% H2O for butan-1-ol and diphenylethanol derivatives, respectively similar with the aggregation-induced emission (AIE) characterized compounds. In the light of the experiment results, it was determined that the R-isomers of carboxylic acids formed more favourable complexes with the chiral selectors when compared to S-isomers.

Synthesis and Reaction of ortho-Benzoquinone Monohemiaminals.

The preparation and reactions of ortho-benzoquinone monohemiaminals are described. The oxidative dearomatization of phenols bearing amino alcohol groups induced N-cyclization to afford ortho-benzoquinone monohemiaminals. The N-cyclization stereoselectively affords the product when a chiral amino alcohol is used as the substituent. The chiral ortho-benzoquinone monohemiaminal undergoes stereoselective Diels-Alder reactions with electron-deficient alkenes, as expected, confirming the promising utility of ortho-benzoquinone monohemiaminals.

Novel hydroxyamides and amides containing D-glucopyranose or D-fructose units: Biological assays in MCF-7 and MDST8 cell lines.

A novel library of 15 compounds, hydroxyamides and amides containing a β-D-glucopyranose (D-Gluc) or a β-D-fructose (D-Fruc) units was designed and synthesized for antiproliferative assays in breast (MCF-7) and colon (MDST8) cancer cell lines. Twelve of them were hydroxyamides and were successfully synthesized from β-D-glucuronic acid (D-GluA). Six of these hydroxyamides which were acetylated hydroxy-β-D-glucopyranuronamide 2a-2f (1st Family) and the other six were their respective isomers, that is, hydroxy-β-D-fructuronamide 3a-3f (2nd Family), obtained by acid-base catalyzed isomerization. These compounds have the general structure, D-Gluc-C=ONH-CHR-(CH2)n-OH and D-Fruc-C=ONH-CHR-(CH2)n-OH, where R=an aromatic, alkyl or a hydrogen substituent, with n=0 or 1. Eight of these contained a chiral aminoalcohol group. Three compounds were amides containing a D-glucopyranose unit (3rd Family). SAR studies were conducted with these compounds. Antiproliferative studies showed that compound 4a, the bromo-amide containing the β-D-glucopyranose ring, potently inhibits the proliferation of the MDST8 cells. Five compounds (2e, 2f, 3d, 3e, and 3f) were shown to potently selectively inhibit the proliferation of the MCF-7 cells. Compound 4b was the only one showing inhibition in both cell lines. In general, the more active compounds were the amides and hydroxyamides containing the β-D-fructose moiety, and containing an alkyl group or hydrogen. Half-inhibitory concentrations (IC50) of between 0.01 and 10 μM, were observed.

Selective fluorescent sensors for malate anion using the complex of phenanthroline-based Eu(III) in aqueous solution

The compounds L1, L2 and D1 based on phenanthroline Schiff base bearing chiral amino alcohol groups had been synthesized and demonstrated. The sensing ability of the compounds in the presence of metal cations (Li+, Na+, K+, Mg2+, Co2+, Mn2+, Zn2+, Cd2+, Hg2+, Al3+, Cr3+, Fe3+, Eu3+) was studied by fluorescent spectroscopy. The experimental results indicated that compounds L1 and D1 could act as selective fluorescent sensors for Cd2+, Zn2+ with fluorescence enhancement and for the Eu3+ ion with fluorescence quenching in aqueous solution. Additionally, the emission properties of the L1–Eu3+ complex could be applied as selective sensor to distinguish malate anion from other carboxylate anions in an aqueous solution.

A highly selective fluorescence-enhanced chemosensor for Al3+ in aqueous solution based on a hybrid ligand from BINOL scaffold and β-amino alcohol

A chemosensor (R)-OH bearing an amino alcohol group was synthesized for the highly selective fluorescent recognition of Al3+ with low limit of detection (16 ppb). “Turn-on” type fluorescence changes were observed upon the addition of Al3+ in aqueous solution. The significant enhancement (35.4-fold) of fluorescence intensity was ascribed to the complex formation between (R)-OH and Al3+ which denoted as the chelation-enhanced fluorescence (CHEF) process.

Synthesis of Aminoalcohols in the Cyclohexa[b]furanic Series

On the basis of previous studies on aminoalcohol derivatives, we sought to synthesize new bicyclic furan derivatives bearing the hydroxyethylamine motif. The cyclohexa[b]furanic skeleton was obtained in two steps. The introduction of a 2-hydroxyethylamine functionality on the 5 and 6 position was rendered difficult by conjugation between the ketone and the aromatic ring. This conjugation was suppressed by reducing the ketone group allowing the easy introduction of the appropriate functional groups on C-4 and C-5 to yield 5-amino-4-hydroxy-2-phenyl-4, 5, 6, 7-tetrahydrobenzo[b]furane (11) incorporating the desired aminoalcohol group.

Novel pyrazolo[1,5- a]pyrimidines as c-Src kinase inhibitors that reduce IKr channel blockade

To improve the in vitro potency of the c-Src inhibitor 1a and to address its hERG liability, a structure–activity study was carried out, focusing on two regions of the lead compound. The blockade of the delayed cardiac current rectifier K + ( I Kr) channel was overcome by replacing the ethylenediamino group with an amino alcohol group at the 7-position. In addition, modifying the substituents at the 5-position and the side chain groups on the amino alcohols at the 7-position enhanced the intracellular c-Src inhibitory activity and increased central nervous system (CNS) penetration. In the present study, 6l exhibited significant in vivo efficacy in a middle cerebral artery (MCA) occlusion model in rats.

Formation of Stable Holographic Polymer Dispersed Liquid Crystal Grating with High Diffraction Efficiency Assisted by in situ Hydrolysis-Condensation of Trialkoxysilylalkyl Group of Methacrylate Component

Stable transmission holographic polymer dispersed liquid crystal grating with reasonably high diffraction efficiency (72%, induction period 576 s) could be prepared via radical network formation of trimethylolpropane triacrylate (only 10 wt %, photo-cross-linkable, further diluted with 10 wt % 1-vinyl-2-pyrrolidone) and 3-methacryloxypropyltrimethoxysilane (80 wt %, non cross-linkable by radical polymerization, but cross-linkable by hydrolysis-condensation) in the presence of 35 wt % TL 203 as a liquid crystal, assisted by simultaneous hydrolysis-condensation of trimethoxysilyl group. The hydrolysis-condensation was induced by moisture in reagents and proton species produced from 3, 3′-carbonylbis[7′-diethylaminocoumarine] as a photo-sensitizer and diphenyliodonium hexafluorophosphate as a photo-initiator. Grating could not be formed for the same system with 3-methacryloxypropyltrimethylsilane (non hydrolyzable and not cross-linkable).Rather decreased efficiency of 3-methacryloxypropyltriethoxysilane system (13% efficiency, 693 s induction period) was remarkably improved to 75% (75 s induction period) by introducing hydrophilic urethane group into the spacer to facilitate easier hydrolysis. The long grating spacing of 0.9 μm indicates very small volume shrinkage. The maximum diffraction efficiency (85%) was observed at 60–70 wt % 3-N-(2-methacryloxyethoxycarbonyl)aminopropyltriethoxysilane, but with a little larger volume shrinkage.Introduction of aminoalcohol group in the spacer could further shorten the induction period to 18 s, but the diffraction efficiency was rather low (20%).

Crystal structures of bis-ligand complexes of copper(II) with 2-[(2-hydroxyethylamino)-methyl]-4,6-dinitrophenol, 2,4-dichloro-6-[(2-hydroxyethylamino)-methyl]phenol, and 2,4-dibromo-6-[(2-hydroxyethylamino)-methyl]phenol

The crystal structures of bis{2,4-dibromo-6-[(2-hydroxyethylamino)-methyl]phenolato}copper (I), bis{2,4-dichloro-6-[(2-hydroxyethylamino)-methyl]phenolato}copper (II), and bis{2-[(2-hydroxyethylamino)-methyl]-4,6-dinitrophenolato}copper (III) in which the metal atom is located at the center of symmetry are determined using X-ray diffraction. Crystals of compounds I and II are isostructural. The copper atom in the structures of compounds I and I coordinates two singly deprotonated bidentate molecules of the ligand through the phenol oxygen atoms and the azomethine nitrogen atoms with the formation of a distorted planar square. In the crystals, complexes I and II form one-dimensional infinite chains along the b axis. In the structure of compound III, the coordination polyhedron of the central atom is an elongated tetragonal bipyramid with the base formed by the azomethine nitrogen atoms and the phenol oxygen atoms. Both vertices of the bipyramid are occupied by the oxygen atoms of the amino alcohol groups of the neighboring complexes, which are related to the initial complex through the center of symmetry. In turn, the oxygen atoms of the alcohol groups of the initial complex are located at the vertices of the coordination bipyramids of the metal atoms of the neighboring centrosymmetric complexes, thus forming infinite polymer chains along the a axis.

Synthesis of Glycidyl Methacrylate-Divinylbenzene Microsheres with Aminoalcohol Groups and Their Adsorption Properties for Boron

New adsorbents (AP, AMP, AHMP and MG) were prepared by introducing the aminoalcohol groups such as 3-amino-1, 2-propanediol, 2-amino-2-methyl-1, 3-propanediol, 2-amino-2-hydroxymethyl-1, 3-propandiol and N-methyl-D (-) -glucamine, respectively, to glycidyl methacrylate-divinylbenzene microspheres (GD) in order to investigate the adsorption properties of boron. All experiments were carried out using a batch method. The amount of OH group introduced to microspheres is the following order: MG>AMP>AHMP>AP. The adsorption of boron showed maximums at pH 6-8 for all adsorbents. The adsorption capacity and the adsorption equilibrium constant were determined using the Langmuir equation. Their adsorption capacities for boron are the following order: AHMP>MG>AP>AMP. Although the amount of OH group introduced to AP is less than AMP, the adsorption capacity of AP is higher than AMP. This result suggests that boron prefers the five-membered chelating ring to the six-membered chelating ring. Boron adsorbed on AMP was easily desorbed using 1 mol·dm-3 hydrochloric acid.

New Synthons for the Synthesis of Lanthanide Containing Macrocyclic Schiff Bases Featuring Substituents Available for Tethering

2,6-Diacetylpyridine substituted with amine or alcohol groups in the 4-position have been prepared from chelidamic acid. The key 4-chloro derivative was synthesized in high yield via a diazo intermediate and was protected as a bis-1,3-dioxane before substitution with various amino alcohol groups. Lanthanide macrocyclic tetra–imine complexes were obtained by a template procedure that leads to stable paramagnetic and/or fluorescent derivatives with anchor groups available for linkage to macromolecules.

Asymmetric reduction of acetophenone with chiral polymeric reagents: Supported sodium borohydride on chiral amino-alcohol bound to a polymer

We have shown the possibility of enantiomeric induction in the reduction of prochiral ketones by NaBH 4 supported on a chiral support. The supports involved polymers (porous or gel type) containing chiral amino-alcohol groups in the side chain. Three chemical ways were tested to obtain these types of support: (i) chemical modification of styrene divinylbenzene copolymers (type 1); (ii) Merrifield synthesis (type 2); or (iii) polymerization of a functional chiral monomer (type 3). The reduction with type 1 copolymers gives good yield (60%) and enantiomeric excess (ee) (56%). The ee increases with introduction of a spacer between the amino and alcohol functions. The ee obtained for the reduction of acetophenone with type 2 copolymers depend on the method used for coupling the amino-alcohol. With triethyl amine the ee is low (38%) but if the cesium salt method is used ee reaches 60%. The cesium salt method in comparison of triethylamine method has the advantage of avoiding quaternary salt formation, this salt acting with NaBH 4 as an ion exchange resin. The best ee (75%) are obtained with supports synthesized by polymerization of a chiral functional monomer. For these supports the yield depends on the texture: 20% for porous support and 50% for gel type support. In comparison model compounds in homogeneous condition lead to very low ee (10%).

Isolation of an Inhibitor for the Independent Mannose 6-Phosphate Receptor Endocytosis of Bovine β-Glucuronidase by Human Fibroblasts

Adsorptive endocytosis of bovine β-glucuronidase by human fibroblasts is mediated by two different membrane receptors: one recognizes phosphomannosyl residues on the enzyme, the other is yet a undefined recognition marker (A. González-Noriega, R. Coutiño, V. M. Saavedra, and R. Barrera (1989) Arch. Biochem. Biophys. 268, 649-658). We have purified a bovine liver inhibitor for the endocytosis of the bovine β-glucuronidase mediated by the recently proposed recognition marker. The inhibitor is partially susceptible to periodate oxidation, can be released from a peptide backbone by mild alkali treatment, can be reduced by sodium borohydride, and can be adsorbed to anionic but not to cationic resins. Although the chemical structure of the isolated marker has not been determined, results indicate a 122-Da molecule which may contain amino alcohol groups and may be found in a 1800-Da glycosidic chain.