Remaining Hydroxy Groups Research Articles

Wychimicins E and F from a rare actinomycete of the genus Cryptosporangium.

Two new spirotetronate class compounds designated wychimicins E (1) and F (2) were isolated from the culture extract of an actinomycete Cryptosporangium sp. RD061707. Their structures were determined through extensive NMR analysis in comparison with wychimicin C. Both compounds lack one hydroxy group in the decalin moiety, and the relative configuration of the remaining hydroxy group was assigned by NMR analysis of triacetylwychimicin E (3). Compounds 1 and 2 showed potent antimicrobial activity against Kocuria rhizophila and Staphylococcus aureus. These compounds were also modestly cytotoxic against P388 murine leukemia cells.

Chlorido(2-{(2-hydroxyethyl)[tris(hydroxymethyl)methyl]amino}ethanolato-κ5 N,O,O′,O′′,O′′′)copper(II)

The title complex, [Cu(C8H18NO5)Cl] or [Cu(H4bis-tris)Cl], was obtained starting from the previously reported [Cu(H5bis-tris)Cl]Cl compound. The deprotonation of the aminopolyol ligand H5bis-tris {[bis(2-hydroxyethyl)amino]tris(hydroxymethyl)methane, C8H19NO5} promotes the formation of a very strong O—H...O intermolecular hydrogen bond, characterized by an H...O separation of 1.553 (19) Å and an O—H...O angle of 178 (4)°. The remaining hydroxy groups are also engaged in hydrogen bonds, forming R 2 2(8), R 4 4(16), R 4 4(20) and R 4 4(22) ring motifs, which stabilize the triperiodic supramolecular network.

Revisiting the Synthesis of Cellulose Acrylate and Its Modification via Michael Addition Reactions.

The synthesis of cellulose acrylate from cellulose with acryloyl chloride has been problematic due to unexpected gelation of the reaction mixture, but we discovered that the use of bulky amines was crucial for the reproducibility of the synthesis of cellulose acrylate. The solubility of the obtained cellulose acrylate depended on the reaction conditions due to the possible cross-linking oxa-Michael reaction between a remaining hydroxy group and the introduced acrylate group. The synthesized cellulose acrylate worked as a useful precursor of chemically modified cellulose materials because it reacted with various functionalized nucleophiles such as secondary amines and thiols as a Michael donor. This method was applied to the synthesis of N-methyl-d-glucamine-modified cellulose that works as an adsorbent for the removal of B(OH)3 in water.

Crystal structures of fac-tri-carbonyl-chlorido-(6,6'-dihy-droxy-2,2'-bi-pyridine)-rhenium(I) tetra-hydro-furan monosolvate and fac-bromido-tricarbon-yl(6,6'-dihy-droxy-2,2'-bi-pyridine)-manganese(I) tetra-hydro-furan monosolvate.

The structures of two facially coordinated Group VII metal complexes, fac-[ReCl(C10H8N2O2)(CO)3]·C4H8O (I·THF) and fac-[MnBr(C10H8N2O2)(CO)3]·C4H8O (II·THF), are reported. In both complexes, the metal ion is coordinated by three carbonyl ligands, a halide ligand, and a 6,6'-dihy-droxy-2,2'-bi-pyridine ligand in a distorted octa-hedral geometry. Both complexes co-crystallize with a non-coordinating tetra-hydro-furan (THF) solvent mol-ecule and exhibit inter-molecular but not intra-molecular hydrogen bonding. In both crystal structures, chains of complexes are formed due to inter-molecular hydrogen bonding between a hy-droxy group from the 6,6'-dihy-droxy-2,2'-bi-pyridine ligand and the halide ligand from a neighboring complex. The THF mol-ecule is hydrogen bonded to the remaining hy-droxy group.

Semisynthesis of Intact Complex-Type Triantennary Oligosaccharides from a Biantennary Oligosaccharide Isolated from a Natural Source by Selective Chemical and Enzymatic Glycosylation.

Attachment of oligosaccharides to proteins is a major post-translational modification. Chemical syntheses of oligosaccharides have contributed to clarifying the functions of these oligosaccharides. However, syntheses of oligosaccharide-linked proteins are still challenging because of their inherent complicated structures, including diverse di- to tetra-antennary forms. We report a highly efficient strategy to access the representative two types of triantennary oligosaccharides through only 9- or 10-step chemical conversions from a biantennary oligosaccharide, which can be isolated in exceptionally homogeneous form from egg yolk. Four benzylidene acetals were successfully introduced to the terminal two galactosides and two core mannosides of the biantennary asialononasaccharide bearing 24 hydroxy groups, followed by protection of the remaining hydroxy groups with acetyl groups. Selective removal of one of the benzylidene acetals gave two types of suitably protected glycosyl acceptors. Glycosylation toward the individual acceptors with protected Gal-β-1,4-GlcN thioglycoside and subsequent deprotection steps successfully yielded two types of complex-type triantennary oligosaccharides.

Pd(II) Complexes Ligated by 1,3-Bis(diphenylphosphino)calix[4]arene: Preparation, X-ray Structures, and Catalyses

syn-1,3-Bis(diphenylphosphino)-2,4-dimethoxycalix[4]arene (7) was synthesized via an Ullmann-type phosphinoylation of the syn-1,3-bis(triflate ester) (2) of p-tert-butylcalix[4]arene, followed by reduction of the phosphinoyl moieties and subsequent methylation of the remaining hydroxy groups. The treatment of diphosphine 7 with 2 molar equiv of PdCl2(MeCN)2 in benzonitrile afforded di-μ-chloro-bridged dinuclear palladium complex 8, formulated as Pd2(7)Cl4, whereas the same reaction conducted in acetonitrile with 1 molar equiv of PdCl2(MeCN)2 yielded mononuclear palladium complex 9, formulated as [Pd(7)Cl(MeCN)]Cl. Complex 9 was transformed into dicationic complex 11, formulated as [Pd(7) MeCN)2](BF4)2, by treatment with AgBF4 in dichloromethane, followed by the addition of acetonitrile. On the other hand, refluxing complex 9 in 1,2-dichloroethane yielded neutral complex 12, formulated as Pd(7)Cl2. In each of the mononuclear complexes, the palladium ion adopts a tetracoordinated square-planar geometry perp...

Positional Effects of Hydroxy Groups on Catalytic Activity of Proton-Responsive Half-Sandwich Cp*Iridium(III) Complexes

Proton-responsive half-sandwich Cp*Ir(III) complexes possessing a bipyridine ligand with two hydroxy groups at the 3,3′-, 4,4′-, 5,5′-, or 6,6′-positions (3DHBP, 4DHBP, 5DHBP, or 6DHBP) were systematically investigated. UV–vis titration data provided average pKa values of the hydroxy groups on the ligands. Both hydroxy groups were found to deprotonate in the pH 4.6–5.6 range for the 4–6DHBP complexes. One of the hydroxy groups of the 3DHBP complex exhibited a low pKa value of <0.4 because the deprotonation is facilitated by the strong intramolecular hydrogen bond formed between the generated oxyanion and the remaining hydroxy group, which in turn leads to an elevated pKa value of ∼13.6 for the second deprotonation step. The crystal structures of the 4- and 6DHBP complexes obtained from basic aqueous solutions revealed their deprotonated forms. The intramolecular hydrogen bond in the 3DHBP complex was also observed in the crystal structures. The catalytic activities of these complexes in aqueous phase reactions, at appropriate pH, for hydrogenation of carbon dioxide (pH 8.5), dehydrogenation of formic acid (pH 1.8), and transfer hydrogenation reactions using formic acid/formate as a hydrogen source (pH 2.6 and 7.2) were investigated to compare the positional effects of the hydroxy groups. The 4- and 6DHBP complexes exhibited remarkably enhanced catalytic activities under basic conditions because of the resonance effect of the strong electron-donating oxyanions, whereas the 5DHBP complex exhibited negligible activity despite the presence of electron-donating groups. The 3DHBP complex exhibited relatively high catalytic activity at low pH owing to the one strong electron-donating oxyanion group stabilized by the intramolecular hydrogen bond. DFT calculations were employed to study the mechanism of CO2 hydrogenation by the 4DHBP and 6DHBP complexes, and comparison of the activation free energies of the H2 heterolysis and CO2 insertion steps indicated that H2 heterolysis is the rate-determining step for both complexes. The presence of a pendent base in the 6DHBP complex was found to facilitate the rate-determining step and renders 6DHBP a more effective catalyst for formate production.

On a Chemoenzymatic Desymmetrization-Ring Expansion Strategy towards Functionalized N-Heterocycles

The direct combination of the desymmetrization of N-heterocyclic meso-diols using lipase from Mucor miehei as biocatalyst and subsequent ring expansion of the optically active products by activation of the remaining hydroxy group gives rise to functionalized nonsymmetrical piperidines in a highly enantio- and dia­stereoselective manner.

Synthesis and Structure of Ethyl 2-[bis(4-hydroxy-2-oxo-2&lt;i&gt;H&lt;/i&gt;-chromen-3-yl)methyl]benzoate

The structure of ethyl-2-[bis(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]benzoate was determined by single-crystal X-ray crystallography. The compound crystallizes in the triclinic crystal system, space group P1 with cell constants: a = 9.4098(5)A, b = 9.5848(5)A, c = 12.8982(7)A, a = 78.556(3)˚, b = 86.524(3)˚, g = 72.310(3)˚; V = 1086.26(10)A 3 , Z = 2. In the title compound, one intramolecular hydrogen bond is formed between the hydroxy group of one coumarin unit and the carbonyl group of the second one; the remaining hydroxy group as well as the carbonyl oxygen atom of the benzoate group are involved in intermolecular hydrogen bonding to the corresponding groups of a neighbouring biscoumarin

FeCl3-mediated Direct Chalcogenation of Phenols

Abstract Direct sulfenylation and selenylation of phenols using a stoichiometric amount of FeCl3 under an oxygen atmosphere has been developed. The chalcogenated phenols were shown to be suitable for preparing S- and Se-containing compounds using the reaction of the remaining hydroxy group.

Comparison of thermal effects of stilbenoid analogs in lipid bilayers using differential scanning calorimetry and molecular dynamics: correlation of thermal effects and topographical position with antioxidant activity

In previous studies it was shown that cannabinoids (CBs) bearing a phenolic hydroxyl group modify the thermal properties of lipid bilayers more significantly than methylated congeners. These distinct differential properties were attributed to the fact that phenolic hydroxyl groups constitute an anchoring group in the vicinity of the head-group, while the methylated analogs are embedded deeper towards the hydrophobic region of the lipid bilayers. In this work the thermal effects of synthetic polyphenolic stilbenoid analogs and their methylated congeners have been studied using differential scanning calorimetry (DSC). Molecular dynamics (MD) simulations have been performed to explain the DSC results. Thus, two of their phenolic hydroxyl groups orient in the lipid bilayers in such a way that they anchor in the region of the head-group. In contrast, their methoxy congeners cannot anchor effectively and are embedded deeper in the hydrophobic segment of the lipid bilayers. The MD results explain the fact that hydroxystilbenoid analogs exert more significant effects on the pretransition than their methoxy congeners, especially at low concentrations. To maximize the polar interactions, the two phenolic hydroxyl groups are localized in the vicinity of the head-group region, directing the remaining hydroxy group in the hydrophobic region. This topographical position of stilbenoid analogs forms a mismatch that explains the significant broadening of the width of the phase transition and lowering of the main phase-transition temperature in the lipid bilayers. At high concentrations, hydroxy and nonhydroxy analogs appear to form different domains. The correlation of thermal effects with antioxidant activity is discussed.

Synthesis of novel dihydroxydiphosphines and dihydroxydicarboxylic acids having a tetra(thio-1,3-phenylene-2-yl) backbone

Novel tetradentate PPh2–OH hybrid ligands 5 and CO2H–OH hybrid ligands 6 have been successfully synthesised from tetra(thio-5-tert-butyl-2-hydroxy-1,3-phenylene) (2 4 ) by replacing the hydroxy groups at both the 2-position and either the 2′-, 2″- or 2‴-position with diphenylphosphino or carboxy groups, after converting into bistriflates 8; the substitution positions of newly introduced substituents are denoted hereafter by superscript 1,n as 5 1, n . Bistriflates 8 1,3 and 8 1,4 can be readily prepared by the regioselective detriflation of tetrakistriflate 7 with tetrabutylammonium fluoride (TBAF), conducted under different conditions. On the other hand, the preparation of bistriflate 8 1,2 requires a four-step process through protection/deprotection. Thus, the silylation of tetraol 2 4 with an excess of 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane gives O,O′- and O″,O‴-disiloxane-1,3-diyl-capped derivative 9. One of the two disiloxane bridges is removed by the treatment with 0.5 mol equiv. of TBAF to give diol 10. Triflation of diol 10, followed by the removal of the remaining disiloxane bridge, affords bistriflate 8 1,2 . Bistriflates 8 are subjected to palladium-catalysed phosphorylation, followed by the reduction of the resulting phosphine oxide 12 1, n to give PPh2–OH hybrid ligands 5 1, n (n = 2–4), while CO2H–OH hybrid ligands 6 1, n (n = 3,4) are obtained from 8 via acetylation of the remaining hydroxy groups, followed by palladium-catalysed methoxycarbonylation of the TfO moieties, and subsequent hydrolysis of the resulting tetraesters 14. X-ray structural analyses of dicarboxylic acids 6 1,3 and 6 1,4 reveal that they form quite different 3D network structures to each other. Interestingly, 6 1,4 constructs a porous channel with a potential for serving as a supramolecular host, by the stacking of its cyclic dimer that is formed by intermolecular hydrogen bondings between the carboxy groups.

Synthesis, characterization, and gas permeation properties of the silyl derivatives of cellulose acetate

Silylation of cellulose acetate having different acetyl contents ( 1: DS Ac = 1.80 and 2: DS Ac = 2.46) was carried out by the reaction of various chlorosilanes [R = SiMe 3 ( a), SiEt 3 ( b), SiMe 2C 8H 17 ( c), SiMe 2C 18H 37 ( d), SiMe 2Ph ( e)] with remaining hydroxy groups of cellulose acetate, and complete substitution was confirmed by 1H NMR and FT-IR spectroscopy. All of the silylated derivatives ( 1a– e and 2a– e) were soluble in common organic solvents and displayed enhanced solubility in relatively non-polar solvents. The onset temperatures of weight loss of 1a– e and 2a– e were higher than 220 °C, indicating fair thermal stability. Silylation of 1 and 2 accompanied a decrease in glass transition temperature, and the decrease became more pronounced as the length of alkyl chain in the silyl group increased. Free standing membranes of 1a– e and 2a– e could be fabricated, and the silylated derivatives displayed remarkably improved gas permeability as compared to 1 and 2. Incorporation of longer silyl groups was more effective to enhance gas permeability, for instance, the P values of 1c were the highest, and its P C O 2 (160 barrers) was 94 times higher than that of 1. The P C O 2 / P N 2 of the silylated polymers ( 1a– e and 2a– e) was appreciably large (19–36), and the values for 1a– c, 2a, and 2c were located either on the upper bound or above it in the plot of permselectivity versus permeability for the CO 2/N 2 gas pair.

Intramolecular rearrangement of 1,3-bistriflate ester of thiacalix[4]arene to 1,2-counterpart: an efficient di-O-protection method for the stereoselective synthesis of anti-1,2-diethers

A net anti-selective dialkylation of the proximal hydroxy groups of thiacalix[4]arene 2 is achieved for the first time via the initial protection of the two proximal hydroxy groups of compound 2 with Tf moieties by intramolecular rearrangement of easily preparable 1,3-bistriflate ester 3 to 1,2-counterpart 4, followed by anti-selective dialkylation of the remaining hydroxy groups with alkyl halides or under the Mitsunobu conditions and subsequent removal of the Tf moieties.

Peptide dithiodiethanol esters for in situ generation of thioesters for use in native ligation

A new approach is described for the general Fmoc-based solid-phase synthesis of C-terminal peptide (thio)esters. One hydroxy group of 2,2-dithiodiethanol (used in large excess) was anchored on trityl resin, and the remaining hydroxy group was loaded with the first amino acid. Standard chain elongation and TFA-based peptide release yielded peptide C-terminal dithiodiethanol esters in good purities. Under standard conditions of native chemical ligation (excess thiol, neutral pH), the dithiodiethanol function is presumably reduced and rearranged (or equilibrated) to the thioester via a 5-membered intermediate. The resulting thioesters are shown to undergo native chemical ligation with N-terminal cysteine peptides. Notably, hydrolysis of the reduced ester is a major competing reaction, especially in the presence of 6 M guanidinium chloride, which is often required for solubilization of large peptide fragments.

Stereoselective dialkylation of the proximal hydroxy groups of calix- and thiacalix[4]arenes.

Treatment of p-tert-butylcalix[4]arene (C1) and its sulfur-bridged analog T1 with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane in the presence of imidazole gives proximally O,O'-disiloxane-1,3-diyl-bridged calixarenes C2 and T2 in excellent yields, respectively. Subsequent base-catalyzed etherification of the remaining hydroxy groups with alkyl halides gives syn- and anti-O'',O'''-dialkylated products, the stereoselectivity of which varies depending on the nature of the macrocycle, as well as the metal cation of the base employed. Thus, conventional calixarene C2 preferentially affords syn compounds of 1,2-alternate conformation (C3) with the aid of tert-BuOK and K(2)CO(3) and anti counterparts of partial-cone conformation (C4) with Cs(2)CO(3). On the other hand, thiacalixarene T2 affords syn compounds of 1,2-alternate conformation (T3) with any of the bases. The disiloxanediyl bridge of the resulting products can readily be removed by treatment with tetrabutylammonium fluoride. Thus, the net process provides an efficient method for the regio- and stereoselective synthesis of proximally dialkylated calix[4]arenes.

SUBPOL: a novel SUcrose-Based Polymer support for solid-phase peptide synthesis and affinity chromatography applications.

A novel SUcrose-Based Polymer support (SUBPOL) with tailored morphology suitable for the use in solid-phase peptide synthesis (SPPS) is described, and its application as a hydrophilic affinity matrix for the specific removal of fibrinogen from human plasma is demonstrated. After suspension polymerization of partly methacrylated 2,1':4,6-di-O-isopropylidene sucrose and subsequent removal of the protecting groups, hydrophilic spherical polymer beads were obtained. The morphology of the resulting resin was controlled by variation of the porogen as well as the average degree of substitution with respect to the methacryloyl groups of the monomer mixture. After introduction of amino groups for a permanent attachment of immobilized peptide ligands, prevention of unintended esterification during SPPS was achieved by silylation of remaining hydroxy groups. Alternatively, a Rink amide linker was introduced prior to SPPS to allow cleavage and subsequent analysis of the peptide assembled on the SUBPOL resins. Two hexapeptides of sequence kwiivw and hffflw, consisting of d-amino acids, as well as a 19-mer peptide corresponding to the sequence GSGVRGDFGSLAPRVARQL of the VP1 protein from the foot-and-mouse disease virus (FMDV) were successfully prepared both manually or in a semi-automated process on SUBPOL resins according to the Fmoc/tBu strategy. Yields and purities were comparable to peptides prepared on commercially available polystyrene resins. A specific affinity adsorbent containing the fibrinogen-binding pentapeptide GPRPK was prepared by SPPS on SUBPOL resins of different morphology, and the strong impact of the affinity matrix on adsorption performance was demonstrated.

Anomeric Anhydro Sugars

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of 3-Sila Derivatives ofl-Ascorbic Acid via Mitsunobu Reaction

Various 3-sila derivatives of L-ascorbic acid were synthesized in satisfactory yields. The ether link was formed by an unusual aspect of the Mitsunobu reaction, without the need of protecting the remaining hydroxy groups.

Kinetics and Thermodynamics of Complex Formation between FeIII and Two Synthetic Chelators of the Dicatecholspermidine Family

This report deals with a kinetic and thermodynamic study of complex formation between FeIII and a new series of synthetic chelators, 2,3- (FR401) and 3,4-dicatecholspermidine (FR295). For the following data, the first value concerns FR295 and the second FR401. Each ligand undergoes five acid-base dissociations, four of which involve the hydroxy groups of the catechol moieties and the final one the central ammonium group. They occur with average at pK2a = 8.40 and 7.95 for the first two hydroxy groups, pK3a = 12.6 and 12.20 for the two remaining hydroxy groups and pK1a = 5.50 and 4.90 for the ammonium group. Complex formation with both chelators occurs rapidly in acidic media (pH < 2), resulting in the second-order complex formation rate constants k1 = 450 M−1 s−1 and 500 M−1 s−1 and first-order complex dissociation rate constants k−1 = 0.82 s−1 and 0.28 s−1. From these two elementary rates, the complex dissociation constant is determined in acidic media: K1 = 1.82·10−3 M and 5.6·10−4 M. The FeIII complexes also undergo five proton dissociations with marked decreases in the catechol pKa value: ΔpK1a = 1.25 and 1.25, ΔpK2a = 6.60 and 6.50, ΔpK3a = 6.55 and 6.95. From ΔpKa and K1, the affinity of both FR295 and FR401 for FeIII is determined: log β = 29 and 31 with pFe = 22 and 25. This new series of chelators is aimed for antibiotic targeting. It proved efficient in inhibiting Plasmodium falciparum growth and delivered iron ions to Gram-negative bacteria.