Hemiaminals as substrates for sulfur ylides: direct asymmetric syntheses of functionalised pyrrolidines and piperidines

Phenyl stabilised chiral sulfur ylides react with five-membered-ring hemiaminals to give functionalised pyrrolidines directly with high enantioselectivity. The reaction can be diverted to give piperidines instead by isolation of the intermediate epoxide and treatment with TMSOTf.     

Quantum mechanical/molecular mechanical free energy simulations of the glutathione S-transferase (M1-1) reaction with phenanthrene 9,10-oxide

Glutathione S-transferases (GSTs) play an important role in the detoxification of xenobiotics in mammals. They catalyze the conjugation of glutathione to a wide range of electrophilic compounds. Phenanthrene 9,10-oxide is a model substrate for GSTs, representing an important group of epoxide substrates. In the present study, combined quantum mechanical/molecular mechanical (QM/MM) simulations of the conjugation of glutathione to phenanthrene 9,10-oxide, catalyzed by the M1-1 isoenzyme from rat, have been carried out to obtain insight into details of the reaction mechanism and the role of solvent present in the highly solvent accessible active site. Reaction-specific AM1 parameters for sulfur have been developed to obtain an accurate modeling of the reaction, and QM/MM solvent interactions in the model have been calibrated. Free energy profiles for the formation of two diastereomeric products were obtained from molecular dynamics simulations of the enzyme, using umbrella sampling and weighted histogram analysis techniques. The barriers (20 kcal/mol) are in good agreement with the overall experimental rate constant and with the formation of equal amounts of the two diastereomeric products, as experimentally observed. Along the reaction pathway, desolvation of the thiolate sulfur of glutathione is observed, in agreement with solvent isotope experiments, as well as increased solvation of the epoxide oxygen of phenanthrene 9,10-oxide, illustrating an important stabilizing role for active site solvent molecules. Important active site interactions have been identified and analyzed. The catalytic effect of Tyr115 through a direct hydrogen bond with the epoxide oxygen of the substrate, which was proposed on the basis of the crystal structure of the (9S,10S) product complex, is supported by the simulations. The indirect interaction through a mediating water molecule, observed in the crystal structure of the (9R,10R) product complex, cannot be confirmed to play a role in the conjugation step. A selection of mutations is modeled. The Asn8Asp mutation, representing one of the differences between the M1-1 and M2-2 isoenzymes, is identified as a possible factor contributing to the difference in the ratio of product formation by these two isoenzymes. The QM/MM reaction pathway simulations provide new and detailed insight into the reaction mechanism of this important class of detoxifying enzymes and illustrate the potential of QM/MM modeling to complement experimental data on enzyme reaction mechanisms.     

Effects of tertiary amine accelerators on curing of epoxide resins

The effects of seven tertiary amine accelerators on curing of bisphenol-type epoxide resins using azelaic acid as a curing agent have been investigated. The structure of the cured resins is characterized and reaction and structure schemes are proposed. The reaction mechanism and the resulting structure of the resin depend on the basicity of the accelerator. With increasing accelerator basicity crosslinking in the cured resin increases. Characterization results indicate that the network structure consists of ether bonds or a mixture of ether and ester bonds; the linear structure consists of only ester bonds. The structure and, therefore, the properties of the cured epoxide resin may thus be regulated by selection of the amine basicity.     

Novel fragmentation reaction of correolide

[reaction: see text] Pentacyclic triterpenoid natural product correolide (1) was converted to ketone 2 via ozonolysis. An unusual fragmentation reaction of ketone 2 with LiCl was discovered. This reaction is general among several similar substrates examined and appears to be specific for the correolide-type E-ring structure (ketone). A mechanism involving a retroaldol reaction, a nucleophilic opening of the epoxide, and a subsequent acetoxy elimination reaction was proposed.     

Theoretical study of the full reaction mechanism of human soluble epoxide hydrolase

The complete reaction mechanism of soluble epoxide hydrolase (sEH) has been investigated by using the B3LYP density functional theory method. Epoxide hydrolases catalyze the conversion of epoxides to their corresponding vicinal diols. In our theoretical study, the sEH active site is represented by quantum-chemical models that are based on the X-ray crystal structure of human soluble epoxide hydrolase. The trans-substituted epoxide (1S,2S)-beta-methylstyrene oxide has been used as a substrate in the theoretical investigation of the sEH reaction mechanism. Both the alkylation and the hydrolytic half-reactions have been studied in detail. We present the energetics of the reaction mechanism as well as the optimized intermediates and transition-state structures. Full potential energy curves for the reactions involving nucleophilic attack at either the benzylic or the homo-benzylic carbon atom of (1S,2S)-beta-methylstyrene oxide have been computed. The regioselectivity of epoxide opening has been addressed for the two substrates (1S,2S)-beta-methylstyrene oxide and (S)-styrene oxide.     

HCAⅡ-inspired Catalysts for Making Carbon Dioxide-based Copolymers: The Role of Metal-hydroxide Bond

The general characteristics of the active center of the catalysts(including zinc-cobalt(III) double metal cyanide complex [Zn-Co(Ⅲ) DMCC]) for the copolymerization reaction of carbon dioxide(CO_2) with epoxide are summarized. By comparing the active center, catalytic performance of the Zn-Co(Ⅲ) DMCC(and other catalysts) with HCAII enzyme in the organism for activating CO_2(COS and CS_2), we proposed that the metal-hydroxide bond(M-OH), which is the real catalytic center of human carbonic anhydride Ⅱ(HCAⅡ), is also the catalytic(initiating) center for the copolymerization. It accelerates the copolymerization and forms a closed catalytic cycle through the chain transfer reaction to water(and thus strictly meets the definition of the catalyst). In addition, the metal-hydroxide bond catalysis could well explain the oxygen/sulfur exchange reaction(O/S ER) in metal(Zn, Cr)-catalyzed copolymerization of COS(and CS_2) with epoxides. Therefore, it is very promising to learn from HCAⅡ enzyme to develop biomimetic catalyst for highly active CO_2/epoxide copolymerization in a well-controlled manner under mild conditions.     

Oligomer–oligomer modification upon the synthesis of epoxy polymers with a “shape-memory” effect

The results of studies of the oligomer–oligomer modification of epoxyamine compositions with amine adducts, oligomers, block oligomers, and oligocyclocarbonates differing in their structure and molecular weight upon hardening under the conditions of a general epoxide–amine polycondensation reaction, and competitive epoxide–amine and cyclocarbonate–amine reactions are given. The parameters of the structure and the elastic-deformation properties required for the preparation of high-quality thermally contracting epoxy polymers with a “shape-memory” and for their reliable application are established.     

The Effects of Intramolecular Hydrogen Bonding on the Reaction of Phenols with Epoxide in the Presence of Nano Calcium Carbonate

The reaction of phenols and dihydroxybenzenes with epoxide in the presence of nano CaCO₃ was studied. Catechol could react with epoxide and gave monochlorohydrin derivative; other dihydroxybenzenes and monomeric phenols had no reaction under the same conditions. The reaction of catechol with epoxide did not occur when nano CaCO₃ was replaced by a normal one. These were attributed to the strong interaction between nano CaCO₃ and the substrate as catechol possessed intrahydrogen bond and excess active hydrogen, which can induce the intramolecular proton transfer via the intramolecular hydrogen bond and promote the reaction of hydroxyl and epoxide. This is an example revealing the unique role of the hydrogen bond played in chemical reactions.     

Reaction mechanism of apocarotenoid oxygenase (ACO): a DFT study

The mechanism of the oxidative cleavage catalyzed by apocarotenoid oxygenase (ACO) was studied by using a quantum chemical (DFT: B3 LYP) method. Based on the available crystal structure, relatively large models of the unusual active-site region, in which a ferrous ion is coordinated by four histidines and no negatively charged ligand, were selected and used in the computational investigation of the reaction mechanism. The results suggest that binding of dioxygen to the ferrous ion in the active site promotes one-electron oxidation of carotenoid leading to a substrate radical cation and a Fe-bound superoxide radical. Recombination of the two radicals, which can be realized in at least two different ways, yields a reactive peroxo species that subsequently evolves into either a dioxetane or an epoxide intermediate. The former easily decays into the final aldehyde products, whereas the oxidation of the epoxide to the proper products of the reaction requires involvement of a water molecule. The calculated activation barriers favor the dioxetane mechanism, yet the mechanism involving the epoxide intermediate cannot be ruled out.     

Scalable ambient synthesis of water‐soluble poly(β‐hydroxythio‐ether)s

Proton transfer polymerization through thiol‐epoxy “click” reaction between commercially available and hydrophilic di‐thiol and di‐epoxide monomers is carried out under ambient conditions to furnish water‐soluble polymers. The hydrophilicity of monomers permitted use of aqueous tetrahydrofuran as the reaction medium. A high polarity of this solvent system in turn allowed for using a mild catalyst such as triethylamine for a successful polymerization process. The overall simplicity of the system translated into a simple mixing of monomers and isolation of the reactive polymers in an effortless manner and on any scale required. The structure of the resulting polymers and the extent of di‐sulfide defects are studied with the help of 13C‐ and ¹H‐NMR spectroscopy. Finally, reactivity of the synthesized polymers is examined through post‐polymerization modification reaction at the backbone sulfur atoms through oxidation reaction. The practicality, modularity, further functionalizability, and water solubility aspects of the described family of new poly(β‐hydroxythio‐ether)s is anticipated to accelerate investigations into their potential utility in bio‐relevant applications. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3381–3386     

Progress towards the total synthesis of trichodermamides A and B: construction of the oxazine ring moiety

Trichodermamides are modified heterocyclic dipeptides that possess a unique 4H-5,6-dihydro-1,2-oxazine ring. Starting from affordable, easily available (-)-quinic acid, the enantioselective synthesis of this oxazine moiety was achieved by an intramolecular epoxide ring-opening reaction by an oxime. [structure: see text]     

Curing of epoxide resins: Model reactions of curing with amines

The reaction of tetrafunctional diamines and bifunctional amines with monoepoxy compounds was investigated by gel-permeation chromatography. At a stoichiometrically equivalent ratio of the functional groups or excess of amine, the consecutive reaction of the epoxide groups with the hydrogen atoms of the amino groups is the only reaction that is taking place; if epoxide is present in excess, the OH groups formed in the reaction are gradually added to the epoxide groups. The ratio of the rate constants of the reaction of the epoxy group with the hydrogen atoms of the primary and secondary amino group was calculated from the concentrations of the reaction products at various excess amounts of amines. The ratio is in good accord with the value calculated from the gel points and limiting stoichiometric ratios in the curing of diepoxides with diamines.     

ALL-trans β-CAROTENE-5,6-EPOXIDE IN THYLAKOID MEMBRANES

All- trans β-carotene-5,6-epoxide has been found in the thylakoid membranes of spinach and of the cyanobacterium Synechococcus vulcanus Copeland. The epoxide was extracted from the thylakoid membranes with acetone, and was isolated by high-performance liquid chromatography (HPLC). The structure of the epoxide was identified by means of mass, Raman, and electronic absorption spectroscopy. Changes in the amount of the epoxide, as a result of epoxidation and (apparent) de-epoxidation reactions in the membranes, were traced by analysis of extracts on HPLC. In isolated thylakoid membranes, only the epoxidation reaction took place. The reaction was caused by irradiation or by the addition of ferricyanide, suggesting that electron transport reactions in the membranes are involved in the epoxidation. In intact spinach leaves, however, both epoxidation and de-epoxidation took place; the extent of epoxidation correlated with the intensity of light incident on the leaves. The epoxidation and de-epoxidation of all- trans β-carotene are contrasted with those of xanthophylls (in the violaxanthin cycle).     

巨大芽胞杆菌环氧水解酶的固定化及其催化性能

考察了多种载体对巨大芽孢杆菌ECU1001环氧水解酶的固定化.以大孔DEAE-纤维素离子交换树脂为载体时,固定化酶的活力回收达70%.进一步考察了温度和pH对固定化酶活力的影响,并使用该固定化酶进行了缩水甘油苯基醚对映选择性水解批次反应.结果表明,在较低的底物浓度下该固定化酶的稳定性较好,10批反应后仍然剩余72.4%的活力.     

A theoretical examination of the acid-catalyzed and noncatalyzed ring-opening reaction of an oxirane by nucleophilic addition of acetate. Implications to epoxide hydrolases

Ab initio and density functional calculations have been performed to gain a better understanding of the epoxide ring-opening reaction catalyzed by epoxide hydrolase. The S(N)2 reaction of acetate with 1S,2S-trans-2-methylstyrene oxide to provide the corresponding diol acetate ester was studied with and without general-acid catalysis. MP2 and DFT (B3LYP) calculations predict, for the noncatalyzed reaction, a central barrier of approximately 20-21 kcal/mol separating the reactants from products depending on which carbon center in the epoxide is undergoing attack. From these gas-phase reactions the immediate alkoxide products are not energetically far below their associated transition states such that the reaction is predicted to be endothermic. Inclusion of aqueous solvation effects via a polarizable continuum model predicts the activation barrier to increase by almost 10 kcal/mol due to the solvation of the acetate ion nucleophile. The activation barrier for the epoxide ring-opening reaction is reduced to approximately 10 kcal/mol when phenol, as the general-acid catalyst, is included in the gas-phase calculations. This is due to the immediate product being the neutral ester rather than the corresponding alkoxide. The transition state in the general-acid-catalyzed reaction is earlier than that for the noncatalyzed reaction and the reaction is highly exothermic. Molecular mechanics calculations of 1S,2S-trans-2-methylstyrene oxide in the active site of murine epoxide hydrolase show two possible binding conformations. Both conformers have the epoxide oxygen forming hydrogen bonds with the acidic hydrogens of the catalytic tyrosines (Tyr381 and Tyr465). These two conformations likely lead to different products since the nucleophile (Asp333-CO(2)(-)) is positioned to react with either carbon center in the epoxide.     

Synthetic studies on erythromycin derivatives: reactivity of the C12-21 alkene

The reactivity of the C12-21 alkene of some erythromycin A derivatives was studied. This double bond was easily oxidized to the corresponding epoxide with excellent stereoselectivity. A single crystal X-ray structure showed that the epoxide moiety was on the same side as the acetonide. When an erythromycin derivative containing a C12-21 alkene was treated with diazomethane a [3+2] cycloaddition affording a pyrazoline occurred. In the case of 6-O-allylated erythromycin derivatives the C12-21 alkene was selectively epoxidized in the presence of the 6-O-allyl moiety. These results show that the C12-21 alkene is an active reaction site, which can be used for useful further modification of erythromycin derivatives.     

Photocatalytic Reaction of Sulfur Dioxide with Heptane in the Gas-phase Over Titanium Dioxide

IntroductionA broad range of orgainc compounds[1 ,2 ]can be oxidized by means of semiconductor pho-tocatalysis with a primary focus on Ti O2 as a durable photocatalyst in recent years.WhenTi O2 is illuminated with the light of energy greater than the semiconductor band gap,elec-tron- hole pairs(e-- h ) are formed in the conduction and thevalence bandsof thesemiconduc-tor,respectively.These charge carriers,which migrate to the semiconductor surface,are ca-pable of activating oxygen species,et…     

Acceleration effect of five‐membered cyclic dithiocarbonate on an epoxy–amine curing system

A bifunctional cyclic five‐membered dithiocarbonate (DTC), having a bisphenol A structure, was found to be an effective accelerator for a epoxy–amine curing system comprised of bisphenol A diglycidyl ether and amine‐terminated polypropylene glycol. The acceleration effect was evaluated by monitoring the time‐dependence of the storage modulus of the reaction mixture with a dynamic mechanical analyzer. The reactions involved in the curing system were investigated in detail by performing a series of model reactions using the corresponding monofunctional monomers. This investigation revealed that (1) DTC reacted with amine rapidly, (2) the reaction afforded the corresponding adduct having a thiourethane and thiol moieties, and (3) the thiol reacted rapidly with epoxide. The thiourethane moiety incorporated into the resulting adduct effectively catalyzed the reaction of epoxide and amine, and this catalysis was the predominant mechanism for the acceleration effect arisen by the addition of DTC. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4606–4611, 2007     

Dihydropyran as a Template for Lactone Synthesis

3,4‐Dihydro‐2H‐pyran (DHP) was efficiently transformed into 4‐thiophenyl‐3,4‐dihydro‐2H‐pyran. This intermediate was converted to the corresponding 1,3‐O,S‐allylic carbanion with t‐butyllithium and selectively alkylated at the carbon α to the sulfur with alkyl halides, an epoxide, and an aldehyde. An one‐pot oxidative elimination of the sulfur fragment using vanadium pentoxide generates the desired β‐substituted α,β‐unsaturated δ‐valero lactone.     

环氧化合物与丝素蛋白化学交联凝胶的结构

对丝素蛋白水溶液与环氧化合物交联剂(PGDE)反应制备的丝素凝胶(CFG)的结构进行了研究.用位相差显微镜观察到CFG具有整体均一的形态结构,而未经PGDE交联的纯丝素凝胶(FG)为颗粒聚集结构.CFG的红外吸收光谱在1104cm^-1处出现PGDE分子中烷醚的吸收峰,而没有出现PGDE两端环醚的特征吸收峰,显示PGDE已经开环交联在丝素蛋白上.氨基酸分析结果显示,酪氨酸、组氨酸和赖氨酸的含量与反应前相比明显减少,PGDE在这些位点与丝素蛋白发生了交联反应.固体¹³CNMR谱观察到酪氨酸羟苯基上的碳发生了化学位移,进一步证实了酪氨酸残基与PGDE发生了化学交联.研究表明,PGDE与丝素蛋白交联形成了分子间交联网络结构,从而使CFG成为较为匀质的凝胶,并有较好的透明度和柔韧性.