Acyclic Diols Research Articles

Synthesis of Conformationally-Locked cis- and trans-Bicyclo[4.4.0] Mono-, Di-, and Trioxadecane Modifications of Galacto- and Glucopyranose; Experimental Limiting 3JH,H Coupling Constants for the Estimation of Carbohydrate Side Chain Populations and Beyond.

Hexopyranose side chains populate three staggered conformations, whose proportions can be determined from the three sets of ideal limiting 3JH5,H6R and 3JH5,H6S coupling constants in combination with the time-averaged experimental coupling constants. Literature values for the limiting coupling constants, obtained by the study of model compounds, the use of the Haasnoot-Altona and related equations, or quantum mechanical computations, can result in computed negative populations of one of the three ideal conformations. Such values arise from errors in the limiting coupling constants and/or from the population of nonideal conformers. We describe the synthesis and analysis of a series of cis- and trans-fused mono-, di-, and trioxabicyclo[4.4.0]octane-like compounds. Correction factors for the application of data from internal models (-CH(OR)-CH(OR)-) to terminal systems (-CH(OR)-CH2(OR)) are deduced from comparison of further models, and applied where necessary. Limiting coupling constants so-derived are applied to the side chain conformations of three model hexopyranosides, resulting in calculated conformer populations without negative values. Although, developed primarily for hexopyranose side chains, the limiting coupling constants are suitable, with the correction factors presented, for application to the side chains of higher carbon sugars and to conformation analysis of acyclic diols and their derivatives in a more general sense.

DNA functionalization by dynamic chemistry.

Dynamic combinatorial chemistry (DCC) is an attractive method to efficiently generate libraries of molecules from simpler building blocks by reversible reactions under thermodynamic control. Here we focus on the chemical modification of DNA oligonucleotides with acyclic diol linkers and demonstrate their potential for the deoxyribonucleic acid functionalization and generation of libraries of reversibly interconverting building blocks. The syntheses of phosphoramidite building blocks derived from D-threoninol are presented in two variants with protected amino or thiol groups. The threoninol building blocks were successfully incorporated via automated solid-phase synthesis into 13mer oligonucleotides. The amino group containing phosphoramidite was used together with complementary single-strand DNA templates that influenced the Watson–Crick base-pairing equilibrium in the mixture with a set of aldehyde modified nucleobases. A significant fraction of all possible base-pair mismatches was obtained, whereas, the highest selectivity (over 80%) was found for the guanine aldehyde templated by the complementary cytosine containing DNA. The elevated occurrence of mismatches can be explained by increased backbone plasticity derived from the linear threoninol building block as a cyclic deoxyribose analogue.

Observations on the Influence of Precursor Conformations on Macrocyclization Reactions

AbstractMacrocycles hold great promise in drug discovery as an underutilized class of lead compounds. The low abundance of these molecules can, in part, be explained by the inherent difficulties in the synthesis of macrocycles and the lack of general methods for their rapid assembly. We have undertaken a research program aimed at developing methods for facile synthesis of macrocycles from simple precursors. The synthesis of two new cyclization precursors is described and the results of their reaction with thionyl chloride are presented and discussed. Whereas one acyclic diol smoothly underwent macrocyclization to afford a mixture of diastereomeric sulfites, subjection of the other precursor to identical reaction conditions resulted in the isolation of the linear dichloride. We hypothesize that there is a difference in the ability of the two molecules to adopt a conformation that is germane to macrocyclization, a proposition that is supported by conformational analyses using molecular mechanics.

Facile access to novel [60]fullerenyl diethers and [60]fullerene-sugar conjugates via annulation of diol moieties.

A general and facile annulation of various diol motifs to [60]fullerene has been developed. This protocol can afford not only 6- to 10-membered-ring fullerenyl diethers in one step from simple acyclic diols but also directly couple [60]fullerene with a variety of structurally diverse sugars. The [60]fullerene-sugar conjugates formed do not require any linker moiety and maintain their inherent structural integrity. The electrochemistry of the fullerenyl diethers and [60]fullerene-sugar conjugates has also been investigated.

Alcohol Cross-Coupling for the Kinetic Resolution of Diols via Oxidative Esterification

We present an organocatalytic C-O-bond cross-coupling strategy to kinetically resolve racemic diols with aromatic and aliphatic alcohols, yielding enantioenriched esters. This one-pot protocol utilizes an oligopeptide multicatalyst, m-CPBA as the oxidant, and N,N'-diisopropylcarbodiimide as the activating agent. Racemic acyclic diols as well as trans-cycloalkane-1,2-diols were kinetically resolved, achieving high selectivities and good yields for the products and recovered diols.

1H NMR spectra of butane‐1,4‐diol and other 1,4‐diols: DFT calculation of shifts and coupling constants

The proton nuclear magnetic resonance (NMR) spectra of butane-1,4-diol, pentane-1,4-diol, (S,S)-hexane-2,5-diol, 2,5-dimethylhexane-2,5-diol and cyclohexane-1,4-diols (cis and trans) in benzene and some other solvents have been analysed. The conformer distribution and the NMR shifts of these diols in benzene have been computed on the basis of the density functional theory, the solvent being included by means of the integral-equation-formalism polarizable continuum model implemented in Gaussian 09. Relative Gibbs energies of all conformers are calculated at the Perdew, Burke and Ernzerhof (PBE)0/6-311+G(d,p) level and NMR shifts by the gauge-including atomic orbital method with the PBE0/6-311+G(d,p) geometry and the cc-pVTZ basis set. Vicinal three-bond coupling constants for the acyclic diols are calculated from the relative conformer populations, the geometries and generalized Karplus equations developed by Altona's group; these correlate well with the experimental values. The solvent dependence of coupling constants for butane-1,4-diol is attributed to conformational change. Coupling constants for the rigid cyclohexane-1,4-diols do not change with solvent and are readily explained in terms of their geometries. The NMR shifts of hydrogen-bonded protons in individual conformers of alkane-1,n-diols show a very rough correlation with the OH · · · OH distances. The computed overall NMR shifts for CH protons in 1,2-diols, 1,3-diols and 1,4-diols are systematically high but correlate very well with the experimental values, with a gradient of 1.07 ± 0.01; those for OH protons correlate less well.

Synthesis of oxathiane and morpholine from acyclic precursors: a modified Mitsunobu reaction

Synthesis of a set of isomeric 2,4,6-triarylmorpholines and 2,6-diaryloxathianes from the corresponding 1,5-diols has been described. The method provides an efficient route to six-membered heterocycles from acyclic diols and is found to be better than Mitsunobu procedure in yield and waste management. In a related study, the ring contraction of pyranone to two isomeric cyclopentenone derivatives through Nazarov reaction has been noticed.

Scientific Opinion on Flavouring Group Evaluation 92 (FGE.92): Consideration of aliphatic acyclic diols, triols, and related substances evaluated by JECFA (68th meeting) structurally related to aliphatic primary and secondary saturated and unsaturated alc

Scientific Opinion on Flavouring Group Evaluation 92 (FGE.92): Consideration of aliphatic acyclic diols, triols, and related substances evaluated by JECFA (68th meeting) structurally related to aliphatic primary and secondary saturated and unsaturated alc

ChemInform Abstract: Thermal and Lewis Acid Promoted Novel Asymmetric Hetero Diels-Alder Reactions of a 1-Thiabuta-1,3-diene System (Thiochalcones) with (-)- Dimenthyl Fumarate.

Thermal and Lewis acid-promoted reactions of thiochalcones with (–)-dimenthyl fumarate gave two 3,4-cis-cycloadducts, 4 and 5, in good yields with 100%endo-diastereoselectivity and with a high level of diastereofacial selectivity. The major product 4 could be obtained stereochemically pure by recrystallization and this, when reduced with LiAlH4, gave the optically active diol 6. The latter was converted into the acyclic diol 8 by Raney-Ni desulphurization.

ChemInform Abstract: Selective Monoalkylation of Acyclic Diols by Means of Dibutyltin Oxide and Fluoride Salts.

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ChemInform Abstract: Enantioselective Synthesis of Functionalized Cyclopentenone and Alkylidenecyclopentane Derivatives from an Acyclic Bisallylic Diol Framework.

ChemInform Abstract: Enantioselective Synthesis of Functionalized Cyclopentenone and Alkylidenecyclopentane Derivatives from an Acyclic Bisallylic Diol Framework.

ChemInform Abstract: Chemo- and Stereoselective Monobenzoylation of 1,2-Diols Catalyzed by Organotin Compounds.

A new facile method for monoacylation of diols has been developed. A variety of cyclic and acyclic diols, in particular 1,2-diols, were selectively monobenzoylated in good yields by the reaction with benzoyl chloride in the presence of a catalytic amount of dimethyltin dichloride and inorganic bases such as potassium carbonate. Furthermore, the method was successfully applied to a kinetic resolution of racemic 1-phenyl-1,2-ethanediol using a chiral organotin catalyst. The ee was dependent on the kind of base, water as an additive, and the reaction temperature.

Flavouring Group Evaluation 64 (FGE.64): Consideration of aliphatic acyclic diols, triols, and related substances evaluated by JECFA (57th meeting) structurally related to aliphatic primary and secondary saturated and unsaturated alcohols, aldehydes, acet

Flavouring Group Evaluation 64 (FGE.64): Consideration of aliphatic acyclic diols, triols, and related substances evaluated by JECFA (57th meeting) structurally related to aliphatic primary and secondary saturated and unsaturated alcohols, aldehydes, acet

The reaction of photochemically generated α-hydroxyalkyl radicals with alkynes: a synthetic route to γ-butenolides

The photomediated generation of α-hydroxyalkyl radicals from simple acyclic and cyclic alcohols, and acyclic diols, and their subsequent carbon-carbon bond forming reaction with propiolate esters and acetylenedicarboxylates, gives a mixture of a β-(hydroxyalkyl)enoate, the result of a formal cis addition, and the unsaturated lactone (γ-butenolide) resulting from the spontaneous cyclization of the corresponding trans addition product. Treatment of the cis adduct with NBS converts it to the same lactone, and so the method overall constitutes a particularly direct route to this important structural unit. Cyclic alcohols give rise to spiro-γ-butenolides. The use of supported photomediators simplifies product isolation and allows for the recovery and reuse of the photomediator.

Ruthenium(salen)‐Catalyzed Aerobic Oxidative Desymmetrization of meso‐Diols and Its Kinetics.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Ruthenium(salen)-Catalyzed Aerobic Oxidative Desymmetrization ofmeso-Diols and Its Kinetics

Chiral (nitrosyl)ruthenium(salen) complexes were found to be efficient catalysts for aerobic oxidative desymmetrization of meso-diols under photoirradiation to give optically active lactols. The scope of the applicability of this reaction ranges widely from acyclic diols to mono-cyclic diols, although fine ligand-tuning of the ruthenium(salen) complexes was required to attain high enantioselectivity (up to 93% ee). In particular, the nature of the apical ligand was found to affect not only enantioselectivity but also kinetics of the desymmetrization reaction. Spectroscopic analysis of the oxidation disclosed that irradiation of visible light is indispensable not only for dissociation of the nitrosyl ligand but also for single electron transfer from the alcohol-bound ruthenium ion to dioxygen.

A more convenient and general procedure for O-monobenzylation of diols via stannylenes: a critical reevaluation of the Bu2SnO method.

A more consistent, straightforward, and economical protocol for generation of stannylene species and their reaction with BnBr leading to products of O-monobenzylation of diols has been set. It has shown to be specially indicated for substrates bearing vicinal trans 1,2-diol moieties on cyclohexane backbones, which are more resistant to these transformations. Such protocol has been successfully applied to myo-inositol derivatives and acyclic diols.

Synthesis and resolution of 2,2-dimethyl-1,3-diphenyl-1,3-propanediol, a new C2-symmetric and conformationally rigid acyclic diol

Diastereomerically pure (+)- and (−)-2,2-dimethyl-1,3-diphenyl-1,3-propanediols were synthesized starting from diethyl malonate and resolved through diesters of (−)-camphanic acid and also N-carbethoxy- l-proline. The absolute configuration of the (−)-enantiomer was established by X-ray crystallography.

Enantioselective properties of Fusarium solani pisi cutinase on transesterification of acyclic diols: activity and stability evaluation

The regio and enantioselectivity of a recombinant cutinase from Fusarium solani pisi was tested on three racemic and one prochiral phenylalkanediols via irreversible transesterification with vinyl acetate. The optimization of the reaction conditions involved the screening of different organic solvents as well as the variation of the substrate concentrations. Thus, the enzymatic activity was checked by measuring initial reaction rates, overall yields, and enantiomeric excess of the reaction products. Only the smaller molecules were recognized by the enzyme, and a denaturing effect of the acyl donor was observed. Nevertheless, a stabilising effect on the enzyme caused by a pre-incubation with the diol was also noted.

Metabolites from the Sponge Plakortis simplex. Part 3: Isolation and Stereostructure of Novel Bioactive Cycloperoxides and Diol Analogues

The known plakortide H ( 1), the novel cycloperoxide polyketides plakortide I ( 2) and J ( 3), and the diol analogues seco-plakortide H ( 4) and seco-plakortide I ( 5), have been isolated from the Caribbean marine sponge Plakortis simplex as their methyl esters 1a– 5a, and their structures fully characterized by spectroscopic and chemical means. The absolute stereochemistry at the three chiral sites C-3, C-4, and C-6 of plakortide H ( 1) and of the novel compounds 2– 5 have been determined by applying the modified Mosher method on certain reaction products. The isolated compounds exhibited good cytotoxic activity against WEHI 164, a murine fibrosarcoma cell line. Cycloperoxide esters and carboxylic acids were found considerably more active than the corresponding acyclic diol analogues.