Asymmetric dihydroxylation of d-glucose derived alpha,beta-unsaturated ester: synthesis of azepane and nojirimycin analogues

The asymmetric dihydroxylation of a d-glucose derived alpha,beta-unsaturated ester 3 afforded syn vicinal diols in good to high diastereoselectivity. The conversion of these vicinal diols to the corresponding cyclic sulfate, regio-, stereoselective nucleophilic ring opening by sodium azide, and LAH reduction afforded amino heptitols 7a,b that were converted to azepane 1c,d and nojirimycin analogues 2c,d.     

Regioselective esterification of vicinal diols on monosaccharide derivatives via Mitsunobu reactions

We have carried out a series of esterification reactions of secondary alcohols derived from d-glucose, d-mannose, and d-galactose via the Mitsunobu reaction. The benzoylation reaction of vicinal diols derived from monosaccharides under Mitsunobu conditions afforded monobenzoates with retention of stereochemistry only. The regioselectivity of these reactions depends on the stereochemistry of the sugar starting material. The Mitsunobu reactions on these diols may be used for the selective protection of other vicinal secondary hydroxyl groups.     

Kinetics and mechanism of the oxidation of some diols by benzyltrimethylammoniumtribromide

The kinetics of oxidation of five vicinal and four non-vicinal diols, and two of their monoethers by benzyltrimethylammonium tribromide (BTMAB) have been studied in 3:7 (v/v) acetic acid-water mixture. The vicinal diols yield the carbonyl compounds arising out of the glycol bond fission while the other diols give the hydroxycarbonyl compounds. The reaction is first-order with respect to BTMAB. Michaelis-Menten type kinetics is observed with respect to diol. Addition of benzyltrimethylammonium chloride does not affect the rate. Tribromide ion is postulated to be the reactive oxidizing species. Oxidation of [1,1,2,2-²H₄] ethanediol shows the absence of a kinetic isotope effect. The reaction exhibits substantial solvent isotope effect. A mechanism involving a glycol-bond fission has been proposed for the oxidation of the vicinal diols. The other diols are oxidized by a hydride ion transfer to the oxidant, as are the monohydric alcohols.     

Regioselective enzymatic acylation of vicinal diols of steroids

Monoacylated derivatives of a complete set of 2,3- and 3,4-vicinal diols of steroids were prepared by regioselective lipase-catalysed transesterification reactions. The enzymes displayed different selectivities towards the vicinal diols depending on the configuration of the hydroxyl groups.     

Capacity gradient anion chromatography with a borate complex as eluent

Complex formation between borate compounds and vicinal diols is well recognized. Generally, in a chemically bonded anion-exchange resin, many hydroxyl groups are introduced on the surface of the resin in order to make the resin hydrophilic. The borate as an eluting reagent also reacts to these hydroxyl groups, and this complex formation decreases the apparent ion-exchange capacity of the column by being dissociated to the anion depending on the eluent pH. In the present work a method is described for the simultaneous determination of anions based on the capacity gradient for suppressed ion chromatography. A Tosoh IC-Anion-PW column and dihydroxyphenylborane–mannitol eluent system were used. To maintain baseline stability, it was helpful to keep the borate concentration constant during a gradient of 16 to 0 mM mannitol as a modifier to prevent the complex formation with the hydroxyl on the resin. The chemical composition of the eluents and gradient profiles are discussed and the application to the analysis of the condensed phosphates with widely varying retention times as food additives in a cheese sample is presented.     

Deuterium NMR studies of inositol liquid crystals [1]

Deuterium NMR investigations are presented on members of two new mesogenic series derived from the naturally occurring stereoisomers myo- and scW/o-inositol. Tetraethers of these two series exhibit thermotropic columnar phases in which the columns are apparently formed by stacked hydrogen bonded dimers of these molecules which chemically are vicinal diols. Deuterium NMR measurements were performed on the tetraoctyl homologues 2e (a cis diol) and 3e (a trans diol) of these series. We have investigated mixtures of these diols with small amounts of benzene-d₆ as probe molecules as well as samples of the neat diol compounds deuteriated at their hydroxyl groups. The results obtained show that the mesophases of both compounds are uniaxial and align partially in a magnetic field upon slow cooling from their isotropic liquids. The alignment is with the director parallel to the field direction indicating that the anisotropic magnetic susceptibility of this mesophase is positive. The deuterium quadrupole splitting of the benzene-d₆ probe in both systems is temperature dependent and in the trans diol 3e it even changes sign. This is interpreted in terms of a model in which the benzene-d₆ probe equilibrates rapidly between two (or more) solvation sites with quadrupole splittings of opposite signs The deuterium spectra of the neat deuterium labelled cis diol 2e exhibit two different signals due to the two deuterons which are located at the axial and equatorial hydroxyl groups. This indicates that there is no fast intra- or intermolecular exchange of the hydroxyl hydrogens. The overall quadrupole splittings of the hydroxyl deuterons in this compound are highly reduced compared to their static values and this is interpreted in terms of motional modes involving both reorientation of the hydroxyl deuterons about their C-O axis and overall reorientation of the molecules (or pairs of molecules) around the columnar axes. The corresponding spectra of the neat deuteriated trans diol 3e exhibit a single spectrum indicating that both hydroxyl deuterons in this compound are equivalent, or very nearly so. Within the mesophase region the spectrum undergoes gradual changes due to the increase in the molecular mobility, but the overall motional narrowing is less than in the cis isomer 2e. Apparently due to stronger hydrogen bonding in the trans isomer 3e the precession of the hydroxyl groups is hindered and a fast molecular reorientation is only possible at high temperatures.     

Investigations into the selective oxidation of vicinal diols to α-hydroxy ketones with the NaBrO3/NaHSO3 reagent: pH dependence, stoichiometry, substrates and origin of selectivity

The NaBrO₃/NaHSO₃ reagent is one of the few oxidizing agents that chemoselectively oxidizes vicinal diols to α-hydroxy ketones with little overoxidation to the corresponding vicinal-dione or dicarboxylic acid. Oxidation reactions performed with this reagent showed strong pH dependence. cis-Vicinal diols reacted faster than trans-vicinal diols to the α-hydroxy ketone product. Hydroxy functional groups at axial ring positions were more readily oxidized than equatorial hydroxy groups. The application of the NaBrO₃/NaHSO₃ reagent for the chemoselective oxidation of vicinal diols was limited to simple systems and failed with more complex monosaccharide compounds probably due to acid catalyzed dehydrogenation reactions. Despite the simple reaction set-up and good selectivity towards the α-hydroxy ketone product, the actual oxidation reaction mechanism is highly complex and postulated to involve at least six different equilibria with a plethora of bromine containing species. A possible oxidation reaction mechanism is discussed.     

Kinetics and mechanism of the oxidation of some vicinal and non-vicinal diols by tetrabutylammonium tribromide

Kinetics of oxidation of five vicinal and four non-vicinal diols, and two of their monoethers, by tetrabutylammonium tribromide (TBATB) has been studied. The vicinal diols yield products arising out of glycol-bond fission, while the non-vicinal diols produce the hydroxycarbonyl compounds. The reaction is first-order with respect to TBATB. Michaelis-Menten type kinetics is observed with respect to diols. The reaction fails to induce the polymerization of acrylonitrile. There is no effect of tetrabutylammonium chloride on the reaction rate. The proposed reactive oxidizing species is the tribromide ion. The effect of solvent composition indicates that the rate increases with increase in the polarity of the solvent. The oxidation of [1,1,2,2-²H₄] ethanediol shows the absence of any primary kinetic isotope effect. Values of solvent isotope effect, k(H₂O)/k(D₂O), at 288 K for the oxidation of ethanediol, propane-1,3-diol and 3-methoxybutan-1-ol are 3.41, 0.98 and 1.02 respectively. A mechanism involving a glycol-bond fission has been proposed for the oxidation of vicinal diols. Non-vicinal diols are oxidised by a hydride-transfer mechanism, as they are monohydric alcohols.     

Asymmetric reduction of α-hydroxy aromatic ketones to chiral aryl vicinal diols using carrot enzymes system

Asymmetric reduction ofα-hydroxy aromatic ketones was carried out by using carrot enzymes system,yielding corresponding chiral vicinal diols with special functional groups.The optimum reaction conditions were obtained after investigation of various influencing factors.Chiral aryl vicinal diols were produced with good yields and excellent enantiomeric excesses under appropriate conditions.Meanwhile,the steric factors and electronic effects of the substituents on the aromatic ring were shown to have an interesting influence on both yield and enantioselectivity.     

Ab initio conformational studies on diols and binary diol-water systems using DFT methods. Intramolecular hydrogen bonding and 1:1 complex formation with water

Studies on the conformational equilibrium for the following diols, ethane-1,2-diol (12EG, CAS 107-21-1), 2R-D-(-)-propane-1,2-diol (12PG, CAS 4254-14-2), (2S,3S)-L-(+)-butane-2,3-diol (L23BD, CAS 19132-06-0), and (2S,3R)-meso-butane-2,3-diol (m23BD, CAS 5341-95-7), are described using Gaussian ab initio calculations involving density functional theory (DFT) methods. We also report in this article results on the stability and conformation for the 1:1 water-diol complex formed by ethane-1,2-diol, propane-1,2-diol, and L- and meso-butane-2,3-diol. The relative stability of the intramolecular (internal) hydrogen bond in a range of diols (n = 2 to 6), based on ab initio geometry optimization and determination of the -O...H- distance, dOH, and -O-H...O- angle, theta, increases through the sequence 1,2 approximately equals 2,3 < 1,3 < 1,4 approximately equals 1,5 approximately equals 1,6, as judged from the bond linearity and -O...H- separation. Quantum mechanical and topological analysis of possible intramolecular hydrogen bonding in this complete series of diols provides convincing evidence for this in diols in which the hydroxyl groups are separated by three or more carbon atoms, that is, in (n, n+m) diols for m > or = 2, but not for ethane-1,2-diol or other vicinal diols, which do not satisfy Popelier's topological and electron density criteria based on the AIM theory of Bader. Based on these criteria it is unlikely that vicinal diols are in fact capable of forming an intramolecular hydrogen bond, in spite of geometric and spectroscopic data in the literature suggesting otherwise.     

Grafting and initiation reactions

Grafting of acrylic monomers onto cellulose substrates in acid aqueous medium using complex of Mn³⁺ ions as a redox initiator is described. Assuming that the /Mn³⁺/ ions react with aldehydes and vicinal diols, the rate of these reactions has been measured spectroscopically. (ESR and visible light) using model compounds. It is concluded that the /Mn³⁺/ grafting onto cellulose is a radical reaction initiated mainly by oxidation of aldehydes at reducing end groups and C-C bond scission of vicinal diols at the end groups and along the cellulose chains. The initiation rates of the Ce⁴⁺, /Mn³⁺/ and VO₂²⁺ redox ions are related to their oxidation potential.     

Molecular interpretation of water structuring and destructuring effects: hydration of alkanediols

Molecular electrostatic potential (MESP) guidelines are employed for understanding the reactivity and hydration patterns in alkanediol molecules. The deeper oxygen lone pair MESP minima indicate stronger basicity of 1,n-diols and 2,4-pentanediol (2,4-PeD) as compared to that of vicinal diols. The existence and strength of the intramolecular hydrogen bond in diols are gauged in terms of the electron density at the bond saddle points. A model named electrostatic potential for intermolecular complexation (EPIC) is used for generating the structures of hydrated complexes, which are subsequently subjected to ab initio calculations at M?ller-Plesset second-order perturbation level of theory. Further, the nature of water...water as well as diol...water interactions is appraised employing many-body energy decomposition analysis. It is seen that water...water interactions are more favorable in vicinal diol...6H(2)O than those in 1,n-diol...6H(2)O (n=3, 4, 5,...) complexes. Exactly opposite trends are shown by diol...water interaction energies. Thus vicinal diols, being more effective at strengthening water...water network, are expected to act as water structuring agents, whereas the non-vicinal diols are expected to be water destructuring agents.     

Domino reactions of 5-deoxy-5-iodo-d-xylo- and -l-arabinofuranose derivatives with organometallic reagents. A way towards polyfunctionalized building-blocks

Domino reactions involving metal-halogen exchange, furanose ring-opening and nucleophilic addition from 3-O-benzyl-5-deoxy-5-iodo-1,2-O-isopropylidene-α-d-xylofuranose and the epimeric l-arabino derivative with various organometallic reagents are reported. In anhydrous conditions, with a large excess of organolithium or Grignard reagents, vicinal diols are obtained with good yields and a fair diastereoselectivity. Interestingly, with α-trimethylsilyl organolithium reagents, the fragmentation of the furanose ring to the substituted pent-4-enal is followed by a Peterson olefination giving dienic compounds in a four-step one-pot process.     

Conformational study and electron density analysis of 9-[tetrahydropyran-3-yl]purine derivatives

A conformational analysis was carried out on cis-6-chloro-9-[2-(2-hydroxyethyl)-2,3,5,6-tetrahydro-4H-pyran-3-yl]purine and several related model compounds at the HF/6-31++G(d,p) and B3LYP/6-311++G(2d,2p) levels, and also using the semiempirical methods AM1 and PM3. The result of this analysis shows that the molecule prefers an axial disposition of the purine ring, with an approximate cis orientation of C4-N9-C1′-H1′ dihedral angle. The stability of this conformation comes mainly from the formation of a C-H?O?H-O intramolecular three-center hydrogen bond. In this structure, the tetrahydropyran oxygen acts as an acceptor, while both H8 of the purine ring and the hydroxylic hydrogen of the hydroxyethyl group act as donors. Also, the equatorial disposition of the hydroxyethyl group in this conformer reduces its repulsions with the purine ring and the tetrahydropyran hydrogens. The quantum theory of atoms in molecules was applied to study the electronic effects produced by the conformational changes, bonding between tetrahydropyran and purine rings, chlorine substitution, and intramolecular hydrogen bonding.     

Photo-Induced Dihydroxylation of Alkenes with Diacetyl,Oxygen, and Water

Herein reported is a photo-induced production of vicinal diols from alkenes under mild reaction conditions. The present dihydroxylation method using diacetyl (= butane-2,3-dione), oxygen, and water dispenses with toxic reagents and intractable waste generation.     

Flavonoids with Vicinal Hydroxyl Groups Inhibit Human Calcitonin Amyloid Formation

Human calcitonin (hCT) is a 32-residue peptide hormone that can aggregate into amyloid fibrils and cause cellular toxicity. In this study, we investigated the inhibition effects of a group of polyphenolic molecules on hCT amyloid formation. Our results suggest that the gallate moiety in epigallocatechin-3-gallate (EGCG), a well-recognized amyloid inhibitor, is not critical for its inhibition function in the hCT amyloid formation. Our results demonstrate that flavonoid compounds, such as myricetin, quercetin, and baicalein, that contain vicinal hydroxyl groups on the phenyl ring effectively prevent hCT fibrillization. This structural feature may also be applied to non-flavonoid polyphenolic inhibitors. Moreover, our results indicate a plausible mechanistic role of these vicinal hydroxyl groups which might include the oxidation to form a quinone and the subsequent covalent linkage with amino acid residues such as lysine or histidine in hCT. This may further disrupt the crucial electrostatic and aromatic interactions involved in the process of hCT amyloid fibril formation. The inhibition activity of the polyphenolic compounds against hCT fibril formation may likely be attributed to a combination of factors such as covalent linkage formation, aromatic stacking, and hydrogen bonding interactions.     

手性芳基邻二醇的不对称合成

具有特定功能基团的手性芳基邻二醇是许多具有特殊功能的药物、农药和信息素的重要中间体,近年来手性芳基邻二醇类化合物的合成与应用研究引起了人们的广泛关注。本文从生物催化不对称合成和化学催化不对称合成两方面综述了近年来手性芳基邻二醇的合成进展,概述了前手性底物上取代基的电子效应和空间效应、手性催化剂的种类和反应体系等因素对合成手性芳基邻二醇产率及光学活性的影响,并对手性芳基邻二醇不对称合成的发展趋势进行了展望。     

Inclusion complexes of alcohols with α-cyclodextrin

Calorimetric studies of the inclusion complexes of straight and branched alcohols and of diols with alpha-cyclodextrin (-CD) have been carried out in water solvent. The data suggest that straight and branched chain alcohols enter the cavity of -CD alkyl end first. The hydroxyl group hydrogen bonds to the outer oxygen ring of the cyclodextrin. For branched chain alcohols the longer alkyl part of the molecule penetrates the -CD cavity up to the hydroxyl group. Diols form two hydrogen bonds to the outer oxygen ring of the cyclodextrin with some penetration into its interior.     

POTENTIAL ENERGY SURFACES OF α-(1→3)-LINKED DISACCHARIDES CALCULATED WITH THE MM3 FORCE-FIELD

The adiabatic conformational surfaces of sixteen 4′,6′,6-trideoxy-α-d-(1→3)-linked disaccharides were obtained using the MM3 force-field at two different dielectric constants. Calculations were carried out on disaccharides with different configurations at C2, C4 and C2′, which are neighbors to the glycosidic linkage, as well as that of the linked carbon (C3). The resulting maps were similar, indicating that the substituents do not play a major role in the conformational features of these disaccharides. However, the preferred minimum conformation and the flexibility were found to be slightly dependant on the configurations of the carbons. Although equatorial bonds and vicinal axial substituents tend to increase the overall flexibility, it was found that these factors can have a cross over effect; i.e., an axial hydroxyl group on C2 may decrease the flexibility if the glycosyl group on C3 is also axial. The relative stabilities of the minimal energy conformations of the 16 compounds also show deviations of the predicted increased stabilities of equatorially substituted compounds over axially substituted ones: these deviations occur mainly for the C2 substituent.