Diol Derivatives Research Articles

Synthesis of the pyruvic acid acetal containing tetrasaccharide repeating unit corresponding to the K82 capsular polysaccharide of Acinetobacter baumannii LUH5534 strain

An efficient synthetic strategy has been developed to achieve a pyruvic acid acetal containing tetrasaccharide repeating unit corresponding to the K82 capsular polysaccharide of Acinetobacter baumannii LUH5534 strain in very good yield. The synthetic scheme involves the use of suitably functionalized monosaccharide thioglycosides as glycosyl donors and a combination of N-iodosuccinimide (NIS) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) as thiophilic glycosylation activator to furnish satisfactory yield of the products with appropriate stereochemistry at the glycosidic linkages. Incorporation of the (R)-pyruvic acid acetal in the D-galactose moiety was achieved in very good yield by the treatment of the diol derivative with methyl 2,2-bis(p-methylphenylthio)propionate in the presence of a combination of NIS and triflic acid.

A New Approach to the Synthesis of Vicinal Diol Derivatives from Eugenol and Evaluation of Biological Activities of Synthetics

A New Approach to the Synthesis of Vicinal Diol Derivatives from Eugenol and Evaluation of Biological Activities of Synthetics

Synthesis and Characteristic Valuation of a Thermoplastic Polyurethane Electrode Binder for In-Mold Coating.

A polyurethane series (PHEI-PU) was prepared via a one-shot bulk polymerization method using hexamethylene diisocyanate (HDI), polycarbonate diol (PCD), and isosorbide derivatives (ISBD) as chain extenders. The mechanical properties were evaluated using a universal testing machine (UTM), and the thermal properties were evaluated using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The PHEI-PU series exhibited excellent mechanical properties with an average tensile strength of 44.71 MPa and an elongation at break of 190%. To verify the applicability of different proportions of PU as an electrode binder, PU and Ag flakes were mixed (30/70 wt%) and coated on PCT substrates, the electrodes were evaluated by four-point probe before and after 50% elongation, and the dispersion was evaluated by scanning electron microscopy (SEM). The electrical resistance change rate of PHEI-PU series was less than 20%, and a coating layer with well-dispersed silver flakes was confirmed even after stretching. Therefore, it exhibited excellent physical properties, heat resistance, and electrical resistance change rate, confirming its applicability as an electrode binder for in-mold coating.

Elucidation of the mechanism of the esterification of boric acid with aliphatic diols: a computational study to help set the record straight.

We present a theoretical investigation on the esterification process for boron ester synthesis, considering boric acid and 2(R),4(S)-pentanediol as model boron and diol derivatives, respectively. We report an unprecedented mechanistic pathway, able to rationalise, in contrast with the reported ones, the relatively low Gibbs energies of activation and the pH dependence experimentally observed in the formation of boron esters. We believe that these findings will improve the possibility to predict cross-link reaction rates of boron esters as a fundamental tool in the rational design of functional materials based on boron-oxygen linkages.

Synthesis and medicinal chemical characterisation of antiproliferative O,N-functionalised isopulegol derivatives.

Benzylation of isopulegol furnished O-benzyl-protected isopulegol, which was transformed into aminodiols via epoxidation followed by ring opening of the corresponding epoxides and subsequent hydrogenolysis. On the other hand, (-)-isopulegol was oxidised to a diol, which was then converted into dibenzyl-protected diol derivatives. The products were then transformed into aminotriols by using a similar method. The antiproliferative activity of aminodiol and aminotriol derivatives was examined. In addition, structure-activity relationships were also explored from the aspects of substituent effects and stereochemistry on the aminodiol and aminotriol systems. The drug-likeness of the compounds was assessed by in silico and experimental physicochemical characterisations, completed by kinetic aqueous solubility and in vitro intestinal-specific parallel artificial membrane permeability assay (PAMPA-GI) measurements.

Convenient Synthesis of the Branched Hexasaccharide Repeating Unit of the Cell Wall O-Antigen of Escherichia coli O80 Strain

AbstractChemical synthesis of a branched hexasaccharide corresponding to the cell wall O-antigen of Escherichia coli (E. coli) O80 strain has been achieved in very good yield with satisfactory stereochemical outcome around the glycosidic linkages by applying a regio- and stereoselective [4+2] block glycosylation strategy. The tetrasaccharide diol derivative was synthesized from suitably functionalized monosaccharide intermediates using sequential stereoselective glycosylations and the disaccharide thioglycoside donor was obtained applying a regio- and stereoselective orthogonal armed-disarmed glycosylation strategy using protected thioglycoside derivatives. A late-stage TEMPO and bis(acetoxy)iodobenzene (BAIB) mediated regioselective oxidation of the primary hydroxyl group of the protected hexasaccharide derivative to the carboxylic acid was achieved leaving secondary hydroxyl groups unaffected.

Gold and Biocatalysis for the Stereodivergent Synthesis of Nor(pseudo)ephedrine Derivatives: Cascade Design Toward Amino Alcohols, Diols, and Diamines

AbstractThe combination of gold(I) and enzyme catalysis has provided access to a series of nor(pseudo)ephedrine derivatives in a regio‐ and stereoselective manner. The approach involves developing IPrAuNTf2‐catalyzed hydration of 1‐phenylprop‐2‐yn‐1‐yl acetate orN‐(1‐phenylprop‐2‐yn‐1‐yl)acetamide, followed by (dynamic) asymmetric biotransamination or bioreduction of the corresponding keto ester or keto amide intermediates. Enzyme actions were completely selective towards the modification of the methyl ketones in a highly stereoselective manner, allowing the synthesis of enantio‐ and diastereomerically enriched products using either racemic or optically active starting materials. Thus, a series of amino alcohol, diol, and diamine derivatives were produced from propargyl esters or amides (57 to 86% isolated yield), the biocatalyst of choice determining the (stereo)selectivity of the overall cascade process (70–99% diastereomeric excess and >98% enantiomeric excess), and providing access to nor(pseudo)ephedrine compounds in a straightforward manner.magnified image

Development of diverse adjustable axially chiral biphenyl ligands and catalysts

Development of highly efficient and practical chiral ligands and catalysts is an eternal theme in asymmetric synthesis. Here, we report the design, synthesis, and evaluation of a new kind of adjustable axially chiral biphenyl ligands and catalysts, in which six model reactions including asymmetric additions of diethylzinc or alkynes to aldehydes in the presence of axially chiral [1,1'-biphenyl]-2,2'-diol ligands, palladium-catalyzed asymmetric cycloadditions in the presence of phosphoramidite ligands, and chiral phosphoric acid-catalyzed asymmetric synthesis of 1,1'-spirobiindane-7,7'-diol derivative and [4+ 3] cyclization were attempted. The results showed that variation of 2,2'-substituent groups could provide different types of ligands and catalysts, and adjustment of substituent groups at the 3,3', 5,5', 6,6'-positions could make ligands and catalysts more efficient in the asymmetric catalytic synthesis. Therefore, our present research should provide a new and useful strategy for development of diverse axially chiral ligands and catalysts.

Transient Stabilization Effect of CO2 in the Electrochemical Hydrogenation of Azo Compounds and the Reductive Coupling of α‐Ketoesters

AbstractThe carbon dioxide (CO2) capture and utilization has attracted a great attention in organic synthesis. Herein, an unpresented transient stabilization effect (TSE) of CO2 is disclosed and well applied to the electrochemical hydrogenation of azo compounds to hydrazine derivatives. Mechanistic experiments and computational studies imply that CO2 can capture azo radical anion intermediates to protect the hydrogenation from potential degradation reactions, and is finally released through decarboxylation. The promotion effect of CO2 was further demonstrated to work in the preliminary study of electrochemical reductive coupling of α‐ketoesters to vicinal diol derivatives. For the electrochemical reductive reactions mentioned above, CO2 is indispensable. The presented results shed light on a different usage of CO2 and could inspire novel experimental design by using CO2 as a transient protecting group.

Transient Stabilization Effect of CO2 in the Electrochemical Hydrogenation of Azo Compounds and the Reductive Coupling of α-Ketoesters.

The carbon dioxide (CO2 ) capture and utilization has attracted a great attention in organic synthesis. Herein, an unpresented transient stabilization effect (TSE) of CO2 is disclosed and well applied to the electrochemical hydrogenation of azo compounds to hydrazine derivatives. Mechanistic experiments and computational studies imply that CO2 can capture azo radical anion intermediates to protect the hydrogenation from potential degradation reactions, and is finally released through decarboxylation. The promotion effect of CO2 was further demonstrated to work in the preliminary study of electrochemical reductive coupling of α-ketoesters to vicinal diol derivatives. For the electrochemical reductive reactions mentioned above, CO2 is indispensable. The presented results shed light on a different usage of CO2 and could inspire novel experimental design by using CO2 as a transient protecting group.

Alternating copolymerization of carbon dioxide with alicyclic epoxides using bimetallic nickel(II) complex catalysts containing benzotriazole-based salen-type derivatives: Catalysis and kinetics

A series of dinuclear nickel complexes based on hexadentate bis(benzotriazole iminophenolate) derivatives with the 1,4-butylene diimine bridging backbone have been synthesized and characterized by single crystal x-ray crystallography. Dinickel complex 1 was demonstrated to be an efficient catalyst for alternating copolymerization of carbon dioxide (CO2) with cyclohexene oxide (CHO) or 4-vinyl-1,2-cyclohexene oxide (VCHO), affording CO2-based polycarbonates with >99% carbonate linkages under the optimized conditions. Particularly, not only the effective catalytic property of binickel complex 1 for CO2-copolymerization of alicyclic epoxides is enabled, but also 1 has been demonstrated to reveal an “immortal” manner in the CO2/VCHO copolymerization. Using the dinickel catalyst 1 in combination with excess diol derivatives as the chain transfer agents could produce very narrowly distributed poly(vinylcyclohexene carbonate) polyols having molecular weights ranging from 5000 to 12000 g/mol. In addition, detailed kinetic studies of the CO2/CHO copolymerization by Ni catalyst 1 were investigated. The results showed that such copolymerization follows a first-order kinetics on both catalyst 1 and CHO concentrations.

Semisynthesis of Hypothemycin Analogues Targeting the C8-C9 Diol.

Hypothemycin, an epoxide derivative of (5Z)-7-oxozeaenol, was used in the semisynthesis of a series of C8-C9 diol derivatives, with many inhibiting TAK1 at submicromolar concentrations. A step-economical approach was chosen, whereby nonselective reactions functionalized the diol to generate multiple analogues in a single reaction. Using this approach, 35 analogues were synthesized using 12 reactions, providing a wealth of information about the role that the C8-C9 diol plays in TAK1 inhibition and cytotoxicity in ovarian and breast cancer cell lines. Monofunctionalized analogues exhibited strong inhibition of TAK1, showing potential for modification of this section of the molecule to assist with solubility, formulation, and other desirable properties. Most analogues were cytotoxic, and three compounds had similar or slightly increased potency with >100-fold improvement in solubility profiles.

Synthesis, DFT study, molecular docking and drug-likeness analysis of the heteroaryl substituted new pregnenolone derivatives

The hybrid molecules having heterocyclic structures in the D-ring of steroids have significant biological activities. Pregnenolone was converted to the hetero-arylidene derivatives by the aldol condensation reaction with two different heteroaromatic aldehydes in the alkali medium. New N- thiocarbomyl and N-acetyl substituted non-fused pyrazoline derivatives were synthesized from the reaction of the resulting hetero-arylidene steroid derivatives with thiosemicarbazide and hydrazine hydrate, respectively, in different reaction conditions. Also, the endocyclic double bond of the 2-pyridinyl substituted hetero-arylidene molecule was converted with stereo- and regioselective dihydroxylation reaction to the new trans-diaxial diol derivative. The theoretical binding affinities of nine compounds with human microsomal cytochrome protein P450 (CYP17; PDB: 1RUK) were evaluated using molecular docking simulations with the AutoDockVina program, and the obtained scores were compared lengthily in the relevant section. Additionally, ADME and drug-likeness analysis were performed for newly synthesized steroids. Finally, using the theoretical MEP analysis over the optimized structures, electrophilic and nucleophilic attack sites of the steroids were clearly determined and evaluated.

Synthesis of nucleoside-substituted carbonate and diol derivatives through the carbon dioxide reaction using polyionic liquid catalysts

Under the combined action of water and polyionic liquids, nucleoside drug intermediates was synthesized through CO2 conversion.

Insight into the corrosion inhibition of new bis-quinolin-8-ols derivatives as highly efficient inhibitors for C35E steel in 0.5 M H2SO4

Both new bis-quinolin-8-ols, namely 5,5′ ((methylenebis(oxy))bis(methylene))bis(quinolin-8-ol)(MBQ), 5,5′-((propane-1,3-diylbis(oxy))bis(methylene))bis(quinolin-8-ol) (PBQ) were prepared in moderate yields through the O-alkylation of 5-(chloromethyl)-quinolin-8-ol hydrochloride by diol derivatives. FT-IR, elemental analysis, and NMR confirmed their molecular structures. The corrosion inhibitory potency of these new bis-quinolin-8-olswas assessed on C35E steel in 0.5 M H2SO4 electrolyte through several approaches such as weight loss, electrochemical measurements, UV–Visible spectroscopy, scanning electron microscopy (SEM) and computational techniques. All outcomes findings confirm that MBQ and PBQ considerably amended protection properties of C35E steel and their performance followed the sequence, PBQ (97.3) > MBQ (95.0) at 0.001 M. Two bis-quinolin-8-ols revealed mixed-type inhibitory activity. The EIS results are described using two the structure model in the presence of bis-quinolin-8-ols compounds. A significant reduction in corrosion attack on the samples exposed to MBQ or PBQ solution was upheld by the surface analysis. The absorption spectra of Uv–visible disclose the occurrence of high interaction between iron atoms and bis-quinolin-8-olsmolecules. The bis-quinolin-8-ols were chemisorbed on the C35E steel surface and followed the Langmuir isotherm model. To get a preferable comprehension of the adsorption of compound species on the steel interface, a detailed modeling investigation was accomplished using molecular dynamics (MD) simulation and DFT calculations.

Role of Epoxide Hydrolases and Cytochrome P450s on Metabolism of KZR-616, a First-in-Class Selective Inhibitor of the Immunoproteasome.

KZR-616 is an irreversible tripeptide epoxyketone-based selective inhibitor of the human immunoproteasome. Inhibition of the immunoproteasome results in anti-inflammatory activity in vitro and based on promising therapeutic activity in animal models of rheumatoid arthritis and systemic lupus erythematosus KZR-616 is being developed for potential treatment of multiple autoimmune and inflammatory diseases. The presence of a ketoepoxide pharmacophore presents unique challenges in the study of drug metabolism during lead optimization and clinical candidate profiling. This study presents a thorough and systematic in vitro and cell-based enzymatic metabolism and kinetic investigation to identify the major enzymes involved in the metabolism and elimination of KZR-616. Upon exposure to liver microsomes in the absence of NADPH, KZR-616 and its analogs were converted to their inactive diol derivatives with varying degrees of stability. Diol formation was also shown to be the major metabolite in pharmacokinetic studies in monkeys and correlated with in vitro stability results for individual compounds. Further study in intact hepatocytes revealed that KZR-616 metabolism was sensitive to an inhibitor of microsomal epoxide hydrolase (mEH) but not inhibitors of cytochrome P450 (P450) or soluble epoxide hydrolase (sEH). Primary human hepatocytes were determined to be the most robust source of mEH activity for study in vitro. These findings also suggest that the exposure of KZR-616 in vivo is unlikely to be affected by coadministration of inhibitors or inducers of P450 and sEH. SIGNIFICANCE STATEMENT: This work presents a thorough and systematic investigation of metabolism and kinetics of KZR-616 and related analogs in in vitro and cell-based enzymatic systems. Information gained could be useful in assessing novel covalent proteasome inhibitors during lead compound optimization. These studies also demonstrate a robust source in vitro test system that correlated with in vivo pharmacokinetics for KZR-616 and two additional tripeptide epoxyketones.

Visible‐light‐Induced Sulfhydrylation and Oxylation of Olefins with Iodine as Catalyst

AbstractHerein, the sulfhydrylation and oxylation of olefins were completed under visible light irradiation with iodine as catalyst, which realized more economical and green chemical conversion because of the absence of metal complexes or organic dyes. A series of bifunctional modifications of olefins were achieved with good yields by using diol derivatives and water as nucleophiles. In addition, the control experiments show that the reaction is a free radical process.

Development of Immobilized SPINOL-Derived Chiral Phosphoric Acids for Catalytic Continuous Flow Processes. Use in the Catalytic Desymmetrization of 3,3-Disubstituted Oxetanes

A family of C2-symmetrical 1,1′-spirobiindane-7,7′-diol (SPINOL) derivatives containing polymerizable styryl units has been prepared through a highly convergent approach. Radical copolymerization o...

Glycerol to renewable fuel oxygenates. Part II: Gasoline-blending characteristics of glycerol and glycol derivatives with C3-C4 alkyl(idene) substituents

The main physico-chemical features, as well as gasoline blending features of eight diol derivatives (1,3-diisopropyl and 1,3-di-tert-butyl glycerol ethers – di-GIPE and di-GTBE; O-isopropyl and O-tert-butyl solketal ethers – SIPE and STBE; isopropylidene ketals of ethylene and propylene glycol – DMD and TMD; cyclic ketals of glycerol with the methyl ethyl ketone and the methyl isobutyl ketone – GBK and GHK) have been estimated in order to reveal the relations between the molecular structures of the compounds and their efficiency as the gasoline oxygenated additives. For the oxygenates, the experimental values of the density, the boiling/melting point, the viscosity and the net heat of the combustion have been obtained. The characteristics of the estimated oxygenate-gasoline blends have involved their density, the calorific value, the fractional composition, the saturated vapor pressure, the research octane number and the motor octane numbers (ON), the oxidation stability, the gum content and the pour point. For di-GTBEs, as the most effective octane booster (among the compounds tested), the effect on the gasoline calorific value has been researched in the combination with the antiknock features improvement, which shows the evident advantages over ethanol and MTBE relatively to ΔAKI/ΔNHOC ratio.

Regio‐ and Enantioselective Synthesis of Trifluoromethyl‐Substituted Homoallylic α‐Tertiary NH2‐Amines by Reactions Facilitated by a Threonine‐Based Boron‐Containing Catalyst

AbstractA method for catalytic regio‐ and enantioselective synthesis of trifluoromethyl‐substituted and aryl‐, heteroaryl‐, alkenyl‐, and alkynyl‐substituted homoallylic α‐tertiary NH2‐amines is introduced. Easy‐to‐synthesize and robust N‐silyl ketimines are converted to NH‐ketimines in situ, which then react with a Z‐allyl boronate. Transformations are promoted by a readily accessible l‐threonine‐derived aminophenol‐based boryl catalyst, affording the desired products in up to 91 % yield, >98:2 α:γ selectivity, >98:2 Z:E selectivity, and >99:1 enantiomeric ratio. A commercially available aminophenol may be used, and allyl boronates, which may contain an alkyl‐, a chloro‐, or a bromo‐substituted Z‐alkene, can either be purchased or prepared by catalytic stereoretentive cross‐metathesis. What is more, Z‐trisubstituted allyl boronates may be used. Various chemo‐, regio‐, and diastereoselective transformations of the α‐tertiary homoallylic NH2‐amine products highlight the utility of the approach; this includes diastereo‐ and regioselective epoxide formation/trichloroacetic acid cleavage to generate differentiated diol derivatives.