Communication: A Facile Synthesis of a Glycoconjugate Cationic Polymer Carrying the 3,6-Branched α-D-Mannosyl Trisaccharide Cluster

Receptor-mediated gene transfection¹ has gained central interests since Wu and Wu² demonstrated successful gene transfection into hepatocytes by using an asialoglycoprotein-poly(L-lysine) complex as a nonviral gene vector. Besides the hepatoma cells possessing galactose-specific receptor proteins, macrophages bearing mannose-specific receptors can also become a target of the gene transfection.^3-5 Though partially mannosylated poly(L-lysine)^3,4 and mannosylated avidin⁵ have been tested for this purpose, development of more effective vectors with higher cytoselectivity is required for gene therapies. As a part of our research efforts to develop and apply artificial glycoconjugate polymers carrying biologically active oligosaccharides,^6-8 our interest has been directed to the potential utility of 3,6-branched α-D-mannoside for the receptor mediated gene transfer targeting macrophages. The 3,6-branched mannosyl trisaccharide is reported to be the much better ligand of mannose-specific binding proteins than mono- and linear oligomannosides.⁹ In this communication, we report a facile synthesis of a glycoconjugate cationic polymer carrying the 3,6-branched α-D-mannoside cluster^10,11 and evaluate its binding affinity to a mannose-specific lectin, concanavalin A.     

Synthesis and Characterization of Photosensitive Phosphorus Based Polymers Containing α,β‐Unsaturated Ketones in the Main Chain

1,3‐Bis(4‐hydroxyphenyl)propenone (BHPP) and 3‐(4‐hydroxy‐3‐methoxy phenyl)‐1‐(4‐hydroxyphenyl)propenone (HMPHPP) were used as monomers for preparing photosensitive phosphorus containing polyesters. The photosensitive monomers BHPP and HMPHPP were prepared respectively by refluxing 4‐hydroxybenzaldehyde and 3‐methoxy‐4‐hydroxybenzaldehyde with 4‐hydroxy acetophenone. The polyesters were synthesized by interfacial polycondensation of photosensitive diols with N‐phenylphosphoramidic dichloride using hexadecyltrimethyl ammonium bromide (HDTMAB) as phase‐transfer catalyst. Copolymers were also prepared by incorporating terephthaloyl chloride in the polymer backbone. The synthesized monomers and polymers were characterized by UV, FT‐IR and ¹H, ¹³C and ³¹P‐NMR spectroscopic techniques. The resulting polymers had inherent viscosities in the range of 0.15–0.51 dL/g and showed good solubility in polar organic solvents. The thermal properties of the polymers were studied by thermogravimetric analysis and differential scanning calorimetry under nitrogen atmosphere. The TGA data revealed that the 10% weight loss occurs at 275–320°C and all the synthesized polymers showed high char residues. DSC studies indicate that these polymers possess T_g in the range of 48 to 64°C. The photosensitive property of the polymers in film and solution state was investigated by ultraviolet spectroscopy. The effect of incorporation of terephthaloyl unit on photocrosslinking and thermal properties of the polymers was also studied.     

Microwave Assisted Synthesis of Biologically Active α-Aminophosphonates Catalyzed by Nano-BF3·SiO2 under Solvent-Free Conditions

Abstract

An efficient and high-yield synthesis of a class of new α-aminophosphonate derivatives as diethyl α-aryl/2-thienyl-α-[2-(phenylthio)phenylamino]methylphosphonates 6a–j in short reaction times from three component coupling reactions (Kabachnik-Fields reaction) of 2-aminodiphenylsulfide 3, substituted phenyl/heterocyclic aldehydes 4a–j, and diethyl phosphite 5 is reported. The reaction proceeds smoothly in the presence of the catalyst, nano-silica-supported boron trifluoride (BF₃·SiO₂) without using solvent under microwave irradiation. The title compounds were tested for in vitro antibacterial and antifungal activities at concentrations of 100 and 200 μg/disc. Minimum inhibitory concentrations (MICs) were also examined.

Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures and tables.     

Stereocontrolled Synthesis of 6′-Deoxy-6′-Fluoro Derivatives of Methyl α-Sophoroside, α-Laminaribioside, α-Kojibioside and α-Nigeroside

Abstract

Sequential tritylation, benzoylation and detritylation of D-glucose, followed by resolution of the crude product by chromatograpEy gave crystalline 1,2,3,4-tetra-O-benzoyl-α- (1) and β-D-glucopyranose (2). Compound 1, 2, and the corresponding methyl α-glycoside 5 were treated with dimethylaminosulfur trifluoride (methyl DAST) to give, respectively, the 6-deoxy-6-fluoro derivatives 3, 4, and 6. Crystalline 2,3,4-tri-O-benzoyl-6-deoxy-6-fluoro-α-D-glucopyranosyl chloride (10) could be obtained from either 3, 4, or 5 by reaction with dichloromethyl methyl ether in the presence of anhydrous zinc chloride. Silver trifluoromethanesulfonate-promoted reaction of 10 with methyl 2-O-(9) and 3-O-benzyl-4,6-O-benzylidene-α-D-glucopyranoside (8) gave the corresponding, (β-linked disaccharidës in high yield. Subsequent deprotection afforded the 6′-deoxy-6′-fluoro derivatives of methyl α-sophoroside (13) and methyl 6′ -deoxy-o′-fluoro-α-laminaribioside (16). Condensation of 8 and 9 with 6-O-acetyl-2,3,4-tri-O-benzyl-α-D-glucopyranosyl chloride in the presence of silver perchlorate was highly stereoselective and produced the α-linked disaccharidës 17 and 21, respectively, in excellent yield. Deacetylation of 17 and 21, followed by fluorination of the resulting alcohols 18 and 22 with methyl DAST and subsequent hydrogenolysis, gave 6′-deoxy-6′-fluoro derivatives of methyl α-kojibioside and methyl α-nigeroside 20 and 24, respectively.     

Synthesis,Transport, and Ionophoric Properties of α,ω-Diphosphorylated Azapodands: XI. Membrane Transport of Metals by Phosphorylated Diazapodands

The membrane transport of rare-earth metals and scandium by new diphosphorylated diazapodands was studied. It was found that the introduction of butyl groups and an additional phosphoryl group on the nitrogen atoms of the terminal aminomethylphosphinoyl groups of azapodands decreases the efficiency of transport of rare-earth metals and increases the selectivity to scandium ion.     

Synthesis of the 3-0, 4-0 and 6-0 Sulfates of Methyl 2-amino-2-deoxy-α-D-Glucopyranoside

Abstract

Starting with methyl 2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside (1), the isomeric methyl 2-amino-2-deoxy-α-D-glucopyranoside 3-, 4-, and 6-sulfates have each been prepared by sulfation of suitably blocked intermediates. Tritylation and acetylation of 1 followed by detritylation gave methyl 3,4-di-0-acetyl-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside (3), having a free 6-hydroxyl group. Base catalyzed 0–4→0–6 acetyl migration provided the corresponding 3,6 di-O-acetyl derivative (4) posessing a free 4-hydroxyl group. Preparation of methyl 4,6-0-benzylidene-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside (9) provided the intermediate bearing a free 3-hydroxyl group. 0-sulfation of 3, 4, and 9 was effected with the pyridine sulfur trioxide complex in dry pyridine.     

Cu(II) Complexes with Optically Active α-Alkylamino Oximes of Caryophyllene Type: Synthesis,Structure, and Properties

Paramagnetic complexes Cu(HL¹)Cl₂ (I), Cu(HL²)Cl₂ · 2H₂O (II), and Cu(HL¹)Br₂ (III) are synthesized by the reaction of copper(II) halides with the optically active -alkylamino oximes HL¹ and HL² of caryophyllene type. Crystal and molecular structures of complex I are determined. The crystals are orthorhombic: a = 9.038(2) Å, b = 11.990(2) Å, c = 11.990(2) Å, V = 2004.8(7) ų, space group P2₁2₁2₁, Z = 4, (calcd) = 1.812 g/cm³, R ₁ = 0.0632. In a mononuclear complex I, the coordination polyhedron of CuCl₂N₂ is a distorted square. The structures of complexes II and III are suggested on the basis of EPR, IR and Raman spectroscopy data.     

Synthesis and Dehydrohalogenation of 3 β-Chloro-5 α,7 α-dibromo-6-ketosteroids of the Stigmastane and Cholestane Series

3-Chloro-5,7-dibromo-6-ketosteroids 5a and 5b are synthesized from -sitosterol (1a) and cholesterol (1b). Dehydrohalogenation of these forms 7-bromo-2,4-dien-6-ones (6a-b), 2,4-dien-6-ones (7a-b), and 14-hydroperoxy-2,4,7-trien-6-ones (8a-b). Woodward hydroxylation of dienone 6a produces 2-iodo-7-bromo-3-acetoxy-⁴-6-ketone 9 and 7-bromo-2,3-diacetoxy-⁴-6-ketone 10. 2-Iodo-3-acetoxy-^4,7,14-trien-6-one 11 is prepared analogously from trienone 8a.     

Synthesis of new α-chloropyridine derivatives of steroidal 3β,5α,6β-triols and 3β,5-dihydroxy-6-ketones

New steroid derivatives containing 6-chloropyridine groups characteristic of the alkaloid epibatidine and neonicotinoid insecticides were synthesized by reacting 3β,5α,6β-trihydroxysteroids or 3β,5-dihydroxy-6ketosteroids with 2-chloro-5-chloromethylpyridine. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 180-182, March-April, 2009.     

Synthesis of an Optically Active Trisubstituted α,β-Butenolide, (S)-4, 6-Dihydroxy-2, 3-dimethyl-2-hexesoic Acid 1, 4-Lactone,from 2-Deoxy-D-ribose

The title compound has been synthesized efficiently from 2-deoxy-D-ribose. The synthesis involves : 1) an aldol like carbon-carbcr. bond formation of (S)-3, 5-dibenzyioxy-2-pentanor.e (8) with a lithium enolate of methyl propanoate, and 2) O-de-benzylation of the aldol adducts (11) for a γ-lactonization followed by β-elimination of the desired butenolide skeleton.     

Synthesis and Characterization of α,ω‐bi[2,4‐dinitrophenyl (DNP)] poly(2‐methoxystyrene) Functional Polymers. Initial Evaluation of the Interaction of the Functional Polymers with RBL Mast Cells

Two series of functional polymers, α,ω‐bi[2,4‐dinitrophenyl][poly(ethylene oxide)‐b‐poly(2‐methoxystyrene)‐b‐poly(ethylene oxide)] (DNP‐PEO‐P2MS‐PEO‐DNP) and α,ω‐bi[2,4‐dinitrophenyl caproic][poly(ethylene oxide)‐b‐poly(2‐methoxystyrene)‐b‐poly(ethylene oxide)] (CDNP‐PEO‐P2MS‐PEO‐CDNP), were synthesized by anionic living polymerization. The polymers were characterized by FT‐IR, ¹H‐NMR and Gel Permeation Chromatography (GPC). The molecular weight distributions for the lower molecular weight functional polymers were slightly broad (1.3–1.5). However, the molecular weight distributions for higher molecular weight polymers were narrower (1.1–1.2). Differential scanning calorimetry (DSC) studies showed thermal transitions indicative of the presence of microphases in the polymer solid state. The polymers were white powders and soluble in tetrahydrofuran. The binding affinity of DNP‐PEO‐P2MS‐PEO‐DNP ligands towards anti DNP IgE was determined by titrations with fluorescently labeled FITC‐IgE. A water soluble CDNP‐PEO‐P2MS‐PEO‐CDNP/DMEG (dimethoxyethylene glycol) complex binds and achieves steady state binding with solution IgE within a few seconds. This strongly suggests that CDNP functional polymers with improved water solubility have potential in therapeutics. Higher molecular weight (water insoluble) CDNP‐PEO‐P2MS‐PEO‐CDNP polymers were electrosprayed as fibers (500 nm) on silicon surface. Fluorescence spectroscopy clearly showed that RBL mast cells were interacting with the fibers suggesting that the cell‐surface receptors were clustered along the fiber surface. These observations suggest that the functional polymers hold promise for developing an antibody detection device.     

Synthesis of 3, 4, 4a, 5, 6, 7, 8, 8a α-Octahydro-4a β, 8α-Dimethyl-2(1H)-Naphthalenones from the Wieland-Miescher Ketone

Conversion of the Wieland-Miescher ketone to a bicyclic dienophile capable of providing the AB rings of the picrasane skeleton of the guassinoids required the introduction of a C-8α methyl group in a 2-decalone. Among the routes explored, the conversion of the Wieland-Miescher ketone to a 4,4a,5,6,7,8-hexahydro-4aβ-methyl-8-methylene-2(3H)-napthalenone and subsequent reduction to a 3,4,4a,5,6,7,8,8aα-octahydro-4aβ,8α-dimethyl-2(1H)-napthalenone proved most useful.     

New Synthetic Methodes 6: Facile High Yield Synthesis of α-Hydroxycarboxylic Esters,by Mild Solvolysis of Trithioorthoesters with HgO/50% Aqueous HBF4/ROH

α-hydroxycarboxylic esters are generally available by the methode of D. Seebach²⁾, by reacting aldehydes with the carbanions of trithioorthoformic esters. An important and quite often limiting step in this procedure is the solvolysis of the trithioorthoesters, mainly done by prolonged refluxing a solution of the α-hydroxytrithioorthoesters in the presence of heavy metal salts^3).     

Synthesis of the Four Configurational Isomers of N-Benzoyl-2, 3, 6-Trtdeoxy-3-C-Methyl-3-Amino-L-Hexose from the (2S, 3R)-Diol Obtained from α-Methylcinnamaldehyde by Fermentation with Baker'S Yeast

Abstract

The erythro and threo chiral C₅ methyl ketones (4) and (5), prepared from the (2S, 3R)-methyl diel (1b), were converted into the phenylsulfenimines (6) and (7), which, in turn, on reaction with allyl-magnesiutn bromide, yielded after acid hydrolysis and benzoylation, the diastereoisomeric C₈-N-aminodiol derivatives (9) and (11), with threo stereochemistry relative to positions 4 and 5. Ozonolysis of (9) and (11) yielded the l-arabino and l-xylo 3-O-methyl branched aminodeoxysugar derivatives (13) and (15), respectively. Using diallylzinc as the reagent, the diastereoisomeric erythro products (8) and (10) were obtained. The latter materials gave the l-ribo-and l-lyxo-(lL-vancosamine) derivatives (12) and (14) upon oxonolysis. The ¹H and ¹³C NMR spectra of the four isomeric aminodeoxysugar derivatives (12)—(15) were discussed.     

The Reaction of 2-Ethoxy-3-Phenylbenzo[D]-1,3, 2-Oxazaphosphorin-6-One with α-Ketocarboxylic Acid Esters: Synthesis of Benzo[d]-1,3,2-Oxazaphosphepine Derivatives

Abstract

The reactions of 2-ethoxy-3-phenylbenzo[d]-1,3,2-oxazaphosphorin-6-one with R-carbonylcarboxylic acids ethyl esters (R = CF₃, Ph, and Me) lead to the formation of seven-membered heterocycles, 2-ethoxy-9-ethoxycarbonyl-2,8-dioxo-3-phenyl-9-R-benzo[d]-1,3,2-oxazaphosphepines.     

Charge Transfer Salt with Substituted Lindquist Polyoxometalate: Synthesis, Crystal Structure, and Physical Properties of α-(BEDT-TTF)6(VW5O19)⋅DMF⋅2H2O

A new charge transfer salt based on bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) and the vanadium substituted Lindquist anion [VW₅O₁₉]^3– was synthesized and characterized by X-ray and spectroscopic analysis. Monoclinic, C2, F _w =3789.2, a=41.5019(5), b=11.2600(2), c=12.7514(2) Å, =101.877(5)°, Z=2, R=0.060, based on 12095 reflections with I>2(I). The structure consists of alternating organic and inorganic layers. The inorganic layer is generated by [VW₅O₁₉]^3– anions, dimethylformamide (DMF) and water molecules. The organic layer, which is generated by three different BEDT-TTF units, belongs to the -type of packing and consists of trimerized chains parallel to the c direction. The compound is a semi-conductor with _{300 K} =1.1 Scm^–1 and E _a =0.1 eV. Polarized reflectance spectra of single crystals were measured over the spectral range from 650 to 25000 cm^–1. FT-NIR Raman spectra of powdered crystals dispersed in KBr pellets were also recorded. Vibrational and electronic features are discussed.     

Synthesis and High-Field NMR of α-D-Arabinofuranosyl-(1→6)-2-AcetamidO-2-Deoxy-O-D-Glucopyranosyl-(1→3)-6-Deoxy-L-Talose,the Repeating Unit of an O-Specific Lipopolysaccharide from Pseudomonas Maltophilia N.C.I.B. 9204

Abstract

Starting from L-rhamnose, benzyl 2,4-di-O-benzyl-6-deoxy-α-L-talopyranoside (7) was prepared by hydrogenolysis of a dioxolane-type benzylidene acetal and used as the aglycon to prepare 2-acetamido-2-deoxy-6-D-glucopyranosyl-(1–3)-6-deoxy-L-talose (13) and the title trisacchafide (20). Due to fast interconvirsion between the α-, β- -pyranose/furanose forms at the reducing end of the molecule in aqueous solutions, the di- and trisaccharides occur as mixtures of four isomers all in significant concentration. By two-dimensional (20) methods, the proton (400) and carbon (100 MHz) NMR spectra of the individual tri-saccharide isomers were completely assigned and interpreted in terms of stereochemistry of the 6-deoxy-L-talose residue.     

The Allyl Group for Protection in Carbohydrate Chemistry,Part 14.1 Synthesis of 2, 3-Di-O-Methyl-4-O-(3, 6-Di-O-Methyl-β-D-Glucopyranosyl)-L-Rhamnopyranose (and its α-Propyl Glycoside): A Haptenic Portion of the Major Glycolipid from Mycobacterium Leprae

Abstract

3, 6-Di-O-methyl-d-glucose was prepared via 5-O-allyl-1, 2-O-isopropylidene-3-O-methyl-αd-glucofuranose and was converted into 2, 4-di-O-acetyl-3, 6-di-o-methyl-dD-glucopyranosy 1 chloride. Condensation of the chlorosugar with methanol or allyl 2, 3-O-isopropylidene-α-l-rhamnopyranoside gave the corresponding crystalline β-glycbsides. The allyl 4-O-(2,4-di-O-acetyl-3, 6-di-O-Tnethyl-β-dD-glucopyranosyl)-2, 3-O-isopropylidene-α-l-rhamnopyranoside was converted into the title compounds and into crystalline 2, 3-di-O-acetyl-4-O-(2, 4-di-O-benzyl-3, 6-di-O-methyl-β-d-glucopyranosyl)-l-rhamnopyranosyl chloride which should serve as an intermediate for the synthesis of the trisaccharide portion of the major glycolipid of Mycobacterium leprae.     

Synthesis and Crystal Structure of α-（1,2,4-Triazol-1H-yl）-ρ-chloro Acetophenone, [ClC6H4COCH2（C2H2N3）]

1 INTRODUCTION Triazole nuclei appear frequently in the struc- tures of various natural products and biologically active compounds, notably thiamine (vitamin B), penicillins, antibiotics such as micrococcin[1], and many metabolic products of fungi and primitive marine animals, including 2-(aminoalky)triazole-4- carboxylic acids[2]. Numerous triazole derivatives exhibit pharmacological activity[3], e.g., 4-amino-N- (triazole-2-yl)benzenesulfonamide is a commercial drug. We report herein …