Ester Exchange Research Articles

Characterization of Oligosaccharides of the Lactosamine Series Derived from Keratan Sulfates by Tandem Mass Spectrometry

Positive- and negative-ion fast-atom bombardment tandem mass spectrometry with collision-induced dissociation (FAB-CID-MS/MS) has been used in the characterization of di-and tetra-saccharides of the lactosamine series from keratan sulfates. FAB-CID-MS/MS of Galβ1-4GlcNAc (L1) exhibited strong fragment ions originating from ring cleavage at the reducing-terminal sugar moiety together with glycosidic bond-cleavage ions, whereas GlcNAcβ1-3Gal (K1) showed strong glycosidic bond-cleavage ions but no ring-cleavage ions. A series of ring-cleavage fragment ions was observed with members of the L-series which have free hydroxyl groups at the C1 and C3 positions. CID-MS/MS spectra of the [M + Na – SO3]+ ion ( m/z 406) from L2 and the [M + Na − 2SO3]+ ion ( m/z 406) from L4 were almost identical with the CID-MS/MS spectrum of the [M + Na]+ ion ( m/z 406) from L1, which indicated that the sugar skeletons of L2 and L4 are the same as that of L1. On the other hand, the CID-MS/MS spectrum of the [M + Na – SO3]+ ion ( m/z 508) from L4 did not resemble that of the [M + Na]+ ion ( m/z 508) from L2. The former showed peaks that were additional to the peaks in the latter. Since these extra peaks were accounted for on the basis of the structure of L3 [Galβ1(6S)-4GlcNAc, S = sulfate], the in-source loss of sulfate groups by ester exchange upon FAB ionization takes place in a dual manner; one reaction at the non-reducing terminal sugar to give L2 and the other at the reducing-terminal sugar to give L3. The CID-MS/MS spectra were characteristic for the tetrasaccharides L1-L1, L2-L2 and L4-L4 while in-source fragmentation confirms the component disaccharides of each tetrasaccharide. The structure of a tetrasaccharide trisulfate was confirmed as L2–L4 and not L4–L2 by CID-MS/MS. Negative-ion FAB-CID-MS/MS spectra of the sulfated di-and tetra-saccharides showed a pattern similar to that of the positive-ion spectra. Subtraction of the CID-MS/MS spectrum of the [M – H]− ion of L2 [Galβ1-4GlcNAc(6S)] from that of the [M – H – SO3]− ion of L4 [Gal(6S)β1-4GlcNAc(6S)] gave several specific ions whose origins were nicely explained on the basis of the structure of L3. The structure of a pentasaccharide consisting of N-acetylneuraminic acid and a tetrasaccharide trisulfate was confirmed, on the basis of FAB-CID-MS/MS, as NeuNAcα2-6L2-L4.

Some Properties of Cyclic Phosphoramidites and Their Phosphites: Phosphitylation, Ester Exchange, and Hydrolysis

Some Properties of Cyclic Phosphoramidites and Their Phosphites: Phosphitylation, Ester Exchange, and Hydrolysis

Reaction of .LAMBDA.3-Vinyliodanes. Generation and Alkylidene-Transfer of Monocarbonyl Iodonium Ylides.

This review summarizes the generation and characterization of monocarbonyl iodonium ylides and their alkylidene-transfer reactions to aldehydes and activated imines. Exposure of Z- (2-acetoxy-l-alkenyl) -λ3-iodanes, prepared stereoselectively by sodium acetate-catalyzed Michael addition of acetic acid to 1-alkynyl-λ3-iodanes, to EtOLi in THE at 78 °C results in ester exchange to generate the labile monocarbonyl iodonium ylides with the liberation of ethyl acetate. The monocarbonyl iodonium ylide acts as an alkylidene-transfer agent to carbonyl compounds to give α, β-epoxy ketones with E-isomers as a major product. Reaction with activated imines affords 2-acylaziridines in good yields. The stereochemical outcome of this aziridination depends on both the activating groups of the imines and the reaction solvents. Measurement of the relative rates of these alkylidene-transfer reactions indicates that the monocarbonyl iodonium ylide is moderately nucleophilic in nature. Wittig olefination of aldehydes with Z- (2-acetoxy-l-alkenyl) -λ3-iodanes, which involves transylidation between monocarbonyl iodonium and phosphonium ylides, is also discussed.

Synthesis, structure and comparative stability of β-hydrazono, oximino methyl ether and imino boronates

β-Hydrazono and oximino ether boronates have been prepared by the sequential lithiation of the corresponding methyl hydrazone or oxime methyl ether, followed by reaction with an iodomethylboronate ester, typically in the form of the pinacol ester. The resulting products have contrasting hydrolytic stabilities. β-Hydrazono boronates are highly sensitive to intramolecularly catalysed hydrolysis, providing the corresponding β-keto boronates in generally high yields; β-oximino ether boronates are stable to silica gel chromatography and show evidence of E–Z-isomerisation. Stable homochiral boronate ester derivatives of β-oximino ethers can be readily prepared by a double transesterification process, via a diethanolamine-mediated pinacol ester exchange, followed by diethanolamine ester hydrolysis–reesterification process with a homochiral diol. β-Imino boronates can be generated in situ by condensation of the corresponding β-keto boronate with a primary amine, however the resulting imine function is highly hydrolytically unstable and cannot be isolated in a pure form.

Energy transfer from phenanthrene to anthracene in a dye-labeled (ethylene-methyl acrylate) copolymer

We describe the synthesis of a branched polyethylene-based polymer containing randomly spaced fluorescent dyes (phenanthrene or anthracene) along the polymer backbone. The dyes were introduced via ester exchange into the ethylene-methyl acrylate copolymer. Fluorescence and fluorescence-decay experiments indicated that the dyes were distributed randomly in a purely amorphous matrix. There was no indication of dye aggregation or of an enhanced local dye concentration of the sort that might be expected in a semicrystalline matrix. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 4169–4175, 1999

Process Improvements in the Production of a Novel Non-Xanthine Adenosine A1 Receptor Antagonist. A “One-Pot” Horner-Emmons Isomerization Reaction

Pilot plant scale synthesis of 2-[3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl-1(6H)-pyridazin-6-one)-1-cyclohexen-1-yl] acetic acid (FR166124) is described. The process involved efficient isomerization of regioisomers produced in a Horner-Emmons reaction and employed ester exchange and hydrolysis with NaOH in MeOH. Challenges encountered in the final purification stage to afford high quality drug substance in pure crystalline form are also described. Process improvements and optimization of each step permitted elimination of column chromatography, resulting in a straightforward, practical, and cost-effective synthesis of FR166124. These methods were successfully scaled up in a pilot plant to give bulk drug suitable for pharmacological and toxicological evaluation.

Synthesis of aliphatic polyesters by controlled ring-opening polymerization of cyclic esters. Characterization, properties, transesterification reactions

The polymerization of (D,L)-Lactide at room temperature in solution using Y(OCH2CH2OiPr)3 and Ln5(μ-O)(OiPr)13 with Ln = La, Sm, Y, Yb as initiators was studied. According to kinetic data, a controlled type polymerization is observed for most of the systems. La μ-oxoisopropoxide is the most reactive initiator, but leads to a substantial broadening of molecular weight distribution at high conversions. The nature of transesterification reactions was studied by SEC, 13C NMR and MALDI-TOF MS techniques. For Sm and Y-μ-oxo initiators only limited intermolecular ester exchange occurs, while with La μ-oxoinitiator and with Y(OCH2CH2OiPr)3 initiator, but after a long time of the polymerization reaction, both inter and intramolecular transesterification occur with formation of cyclics.

ChemInform Abstract: Aziridination of Activated Imines with Monocarbonyl Iodonium Ylides Generated from (Z)‐(2‐Acetoxyvinyl)iodonium Salts via Ester Exchange: Stereoselective Synthesis of 2‐Acylaziridines.

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Gas generation mechanism due to electrolyte decomposition in commercial lithium-ion cell

Abstract To elucidate the gas generation mechanism due to electrolyte decomposition in commercial lithium-ion cells after long cycling, we developed a device which can accurately determine the volume of generated gas in the cell. Experiments on LixC6/Li1−xCoO2 cells using electrolytes such as 1 M LiPF6 in propylene carbonate (PC), dimethyl carbonate (DMC), ethyl methyl carbonate (EMC), and diethyl carbonate (DEC) are presented and discussed. In the nominal voltage range (4.2–2.5 V), compositional change due mainly to ester exchange reaction occurs, and gaseous products in the cell are little. Generated gas volume and compositional change in the electrolyte are detected largely in overcharged cells, and we discussed that gas generation due to electrolyte decomposition involves different decomposition reactions in overcharged and overdischarged cells.

Condensative chain polymerization. II. Preferential esterification of propagating end group in Pd-catalyzed CO-insertion polycondensation of 4-bromophenol derivatives

For a development of condensative chain polymerization where polycondensation proceeds from an initiator in a chain polymerization manner to yield polymer with a defined molecular weight and a narrow molecular weight distribution, the Pd-catalyzed polycondensation of 4-bromophenol derivatives with CO is studied. Model reactions showed that monomer reacted the polymer terminal Br preferentially compared to the monomer Br, but that the ester exchange reaction of polymer backbone with monomer phenoxide occurred in some extent. In the polymerization of 4-bromo-2-n-octylphenol with CO using 4-bromo-2,6-dimethylphenyl benzoate as an initiator, the molecular weight of polymer increased in proportion to time up to 30 min. The GPC elution curves showed that oligomers were produced from the initiator.

Condensative chain polymerization. II. Preferential esterification of propagating end group in Pd‐catalyzed CO‐insertion polycondensation of 4‐bromophenol derivatives

For a development of condensative chain polymerization where polycondensation proceeds from an initiator in a chain polymerization manner to yield polymer with a defined molecular weight and a narrow molecular weight distribution, the Pd-catalyzed polycondensation of 4-bromophenol derivatives with CO is studied. Model reactions showed that monomer reacted the polymer terminal Br preferentially compared to the monomer Br, but that the ester exchange reaction of polymer backbone with monomer phenoxide occurred in some extent. In the polymerization of 4-bromo-2-n-octylphenol with CO using 4-bromo-2,6-dimethylphenyl benzoate as an initiator, the molecular weight of polymer increased in proportion to time up to 30 min. The GPC elution curves showed that oligomers were produced from the initiator. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2607–2618, 1999

The nature of secondary crystallization in poly(ethylene terephthalate)

The nature of secondary crystallization in poly(ethylene terephthalate) (PET) was examined during isothermal crystallization and subsequent melting by time-resolved synchrotron small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC) and temperature modulated DSC (MDSC) techniques. In one experiment, the process of isothermal crystallization was sustained over 72h to induce a relatively large crystallinity (46%, by weight). The purpose of this experiment was to resolve the issue of controversial assignment for the crystal lamellar thickness (lc) by the correlation function analysis of the SAXS data. Results suggest that a two-stage decrease mechanism exists in both long period (L) and lc during isothermal crystallization: (1) a significant decrease in the initial stage (primary crystallization dominant), and (2) a much slower decrease in the later stage (secondary crystallization dominant) that is nearly linear with log time. We attribute this behavior to the formation of thinner separate stacks of lamellae between the primary stacks by secondary crystallization. Both secondary and primary stacks can undergo a great deal of crystal perfection and rearrangement with time. From DSC measurements, a triple-melting behavior was observed in the samples crystallized at 205 and 215°C for 1h, and a double-melting behavior at higher temperatures of 225 and 231°C for 2h. Temperature scanning SAXS and MDSC directly characterize aspects of crystal perfection and melting. Consistent with some of the literature, we confirm that for short annealing (∼hour) at 200–220°C, the first (low) endotherm is related to melting of secondary crystals, the middle endotherm is due to melting of primary crystals, and the third endotherm is due to melting of crystals reorganized during heating. With prolonged crystallization at 231°C for 24 and 72h, a single higher melting endotherm was observed even though SAXS experiments indicate a slight decrease in average lamellar thickness. In PET, ester exchange reactions contribute to unusual high mobility, allowing chains to avoid topological constraints such as entanglements and tie chains. The results suggest that the change in population of tie molecules in the non-crystalline phase reduces the entropy of melting causing an increase in Tm, and that this overwhelms the contribution of the decrease in lc.

Transesterification of oligomeric dialkyl phosphonates, leading to the high‐molecular‐weight poly‐H‐phosphonates

Polycondensation of 1,10-decanediol with dimethyl-H-phosphonate taken in excess leads to oligomers with methyl-H-phosphonate end groups. The polytransesterification of the resulting oligomer as well as the related model reactions were studied. The synthesis of poly(decamethylene-H-phosphonate) was analyzed and the final product had Mn = 1.4–1.9 104 (from end groups, vpo, and Mn of the derived polymers). The exchange of the ester groups between two homoesters (dimethyl and diethyl phosphonates) used as models, conducted at r.t. and catalyzed by metal alkoxide provides mixed (hetero) ester in a few minutes. If the concentration of the catalyst is not high enough, then the reaction does not go to equilibrium, because the alcoholate anions are converted into the anions of monoesters of the H-phosphonic acid, catalytically inactive at this temperature. However, these monoesters become catalytically active at higher temperature, i.e., at the conditions used for preparing higher molecular-weight products by transesterification. The apparent rate constants (k) of the ester exchange catalyzed by monoester salt (modeling the propagation step in polytransesterification) were determined by two independent methods; at 130°C k ∼ 1.0 · 10−2 mol−1 · L · s−1. The detailed study of the model polytransesterification, and particularly of the polymer end groups appearance and disappearance (studied by 1H-, 13C-, and 31P-NMR) allowed postulation of the reaction mechanism and confirmed our previous work, describing formation at these conditions of polymers with Mn > 104. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1365–1381, 1999

Aziridination of Activated Imines with Monocarbonyl Iodonium Ylides Generated from (Z)-(2-Acetoxyvinyl)iodonium Salts via Ester Exchange: Stereoselective Synthesis of 2-Acylaziridines.

Monocarbonyl iodonium ylides, generated in situ from (Z)-(2-acetoxyvinyl)iodonium salts via an ester exchange reaction with EtOLi, undergo alkylidene transfer reactions to activated imines yielding 2-acylaziridines in good yields. The stereochemical outcome of this aziridination was shown to be dependent on both the activating groups of the imines and the reaction solvents: that is, the aziridination of N-(2,4,6-trimethylbenzenesulfonyl)imines in THF affords cis-aziridines as a major product while that of N-benzoylimines in THF-DMSO or THF gives the trans isomer stereoselectively.

Theoretical Prediction of 31P NMR Chemical Shifts of Intermediates in Phosphoryl Ester Exchange and N → O Migration Reactions of Dialkyloxyphosphoryl Amino Acid

Based on a detailed ab initio study on the reaction mechanism of phosphoryl ester exchange and N → O migration reactions of dimethyloxyphosphoryl-threonine, ab initio GIAO magnetic shielding calculations have been carried out on the predicted stable intermediate and the corresponding reactant and product. The 31P NMR chemical shift of the most stable penta-coordinate phosphorus intermediate has been predicted as about –71 ppm. The theoretical results may lead to a possible way to experimentally examine our predictions and to monitor the most stable intermediate during the reaction process.

Theoretical Prediction of 31P NMR Chemical Shifts of Intermediates in Phosphoryl Ester Exchange and N → O Migration Reactions of Dialkyloxyphosphoryl Amino Acid

Based on a detailed ab initio study on the reaction mechanism of phosphoryl ester exchange and N → O migration reactions of dimethyloxyphosphoryl-threonine, ab initio GIAO magnetic shielding calculations have been carried out on the predicted stable intermediate and the corresponding reactant and product. The 31P NMR chemical shift of the most stable penta-coordinate phosphorus intermediate has been predicted as about –71 ppm. The theoretical results may lead to a possible way to experimentally examine our predictions and to monitor the most stable intermediate during the reaction process.

Triglycerides are more important in atherosclerosis than epidemiology has suggested

Epidemiology can be a useful guide to risk prediction. If, for example, the value of serum cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides as predictors of future CHD events is considered, then generally the triglyceride level measured on a single occasion will add little to the prognostic information contained in cholesterol and HDL cholesterol. The serum triglyceride concentration is, however, often more strongly correlated with future CHD incidence in univariate analysis than is serum cholesterol. However, in multiple logistic regression analysis, particularly when HDL cholesterol is included, the strength of the apparent independent relationship between triglycerides and CHD incidence is weakened often to the point of insignificance in individual trials, although it is still evident on meta-analysis of all the epidemiological trials in which both HDL cholesterol and triglyceride levels were measured. The erosion of the relationship between triglycerides and CHD incidence when HDL is included in multiple logistic regression analysis is to some extent is an artefact of the greater biological variation of triglyceride concentrations compared with HDL cholesterol. When allowance is made for this triglycerides can have more predictive power than HDL. Important clinical decisions are generally not based on single measurements, but on a series which reduces the effect of biological variation. However, even more importantly epidemiology cannot tell us that lowering cholesterol or raising HDL cholesterol levels will have more therapeutic benefit than decreasing triglyceride levels. That can only be established in clinical trials. An overview of trials involving drugs, which have as their principal action triglyceride-lowering, revealed them to decrease CHD incidence as much as statins. In the trials the drugs, which principally lowered triglycerides, also produced small decreases in serum cholesterol. The decrease in CHD incidence was, however, more than would be predicted from a similar reduction in cholesterol achieved with statins. Epidemiology can thus be a poor guide to clinical decisions. Furthermore the epidemiological relationship between cholesterol, triglycerides, HDL and CHD gives us only limited insight into the mechanisms by which these lipids and lipoproteins are involved in atherogenesis and their relative importance in this process. Thus evidence from clinical studies linking hypertriglyceridaemia with potentially important atherogenic factors such as intermediate density lipoproteins, small dense LDL and increased cholesteryl ester exchange may provide a greater understanding of atherogenesis and potential sites of therapeutic intervention than epidemiology. There is thus evidence for the therapeutic value of lowering triglycerides and an emerging view that triglyceride-rich lipoproteins are frequently crucial in atherogenesis.

MALDI-MS analysis of pyrolysis products from a segmented polyurethane

A segmented polyurethane consisting of 4,4′-methylenebis-(phenylisocyanate), (MDI), poly(butylene adipate) (PBA) and 1,4-butanediol (BDO) was subjected to low temperature pyrolysis. Polymer samples were pyrolyzed in open-ended Pyrex tubes placed at the end of the carrier gas inlet line in a gas chromatograph. Pyrolysis was carried out under argon flow in the temperature range 250–325°C. After pyrolysis, the residue in the pyrolysis tube was analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Several different series of oligomeric pyrolysis products were observed over the mass range ~800–10000 Da. Linear polyester oligomers were detected having hydroxyl and/or vinyl end groups. Cyclic polyester oligomers were also observed. At lower pyrolysis temperatures, some of the pyrolysis products contained the MDI and BDO moieties. The pyrolysis products can be explained by two principal mechanisms. The first is dissociation of the urethane linkage (or `depolymerization'), which yields products with isocyanato and hydroxyl end groups. The second is ester exchange, which produces the cyclic oligomers. At the higher pyrolysis temperatures, dehydration occurs to yield products with unsaturated end groups. The use of MALDI-MS to examine higher mass pyrolysis products of a polyurethane and a polyester has been demonstrated. We expect that this approach will have numerous applications in studying the pyrolysis products and degradation mechanisms of various synthetic polymers.

Synthesis, Characterization and Degradation of Poly(silyl ester)s

To investigate the effects of sterics and polymer backbone composition upon the rates of hydrolytic degradation of polymers containing trialkyl-substituted silyl ester linkages, six poly(silyl ester)s with molecular weights typically ranging from 5000 to 15000 Da were synthesized through transsilylation ester exchange reactions of alkyl or aryl bis(trimethylsilyl)esters with methyl- and isopropyl-substituted bis(chlorosilyl)hexanes to give trimethylsilyl chloride as the condensate. Characterization of the poly(silyl ester)s included infrared spectroscopy (IR), 1H NMR, 13C NMR, and 29Si NMR INEPT spectroscopies, size-exclusion chromatography (SEC), differential scanning calorimetry, and thermogravimetric analysis. Both 29Si NMR and SEC were employed to monitor the polymerization and the degradation experiments. As expected, the relative stability of the silyl ester bonds toward hydrolysis increased with increased steric hindrance of the substituents attached to the silicon atoms. The incorporation of p-phenylene groups into the polymer backbone allowed for the formation of crystalline domains, which in turn greatly increased the stability toward hydrolytic degradation of the polymers in the solid state. Hydrolysis of the polymers containing diisopropyl-substituted silyl esters gave small molecules; however, degradation of the dimethyl-substituted poly(silyl ester)s as solids in air resulted in the formation of poly(dimethylsilylhexylene siloxane) from the spontaneous condensation of 1,6-bis(dimethylhydroxysilyl)hexane.

Phase behavior of blends of poly(ethylene terephthalate) with liquid‐crystalline polymers

AbstractPoly(ethylene terephthalate) (PET) was melt blended with several liquid‐crystalline polymers (LCPs), both with and without Ti(OBu)4 catalyst. The LCPs, referred to as VA, LC5, LC3, and SBH, respectively, were Vectra‐A950, Rodrun LC‐5000, Rodrun LC‐3000, and a laboratory copolyester of sebacic acid (S), 4,4′‐diacetoxybiphenyl (B), and 4‐acetoxybenzoic acid (H). Their degree of aromaticity decreases in that order. The phase behavior and the morphology of the blends were studied by differential scanning calorimetry and scanning electron microscopy. All the LCPs retard the dynamic crystallization of PET. The lower the LCPs degree of aromaticity, the more pronounced was the effect. It was not possible to obtain any evidence of ester exchange reactions by the reactive blending of PET with VA. On the contrary, appreciable changes of phase behavior and morphology were observed under comparable conditions for the other blends. With LC5 and LC3, the transesterification process predominantly involved the ET‐rich phase of those polymers. Extensive transesterification occurred between PET and SBH, as proven by the gradual formation of a quasi homogeneous material, with lowered temperatures and enthalpies of fusion and crystallization. For blends with more than 25% SBH, homogenization is followed by the segregation of a new, highly aromatic phase.