Methyl transfer from a hydrophobic vitamin B12 derivative to arsenic trioxide

The methylation reaction of arsenic trioxide conducted at 37 °C and pH 7.0 for 24 h using hydrophobic methylated vitamin B₁₂, (methyl) (aquo) heptamethylcobyrinate perchlorate, CH₃B₁₂ ester, as a methyl donor in the presence of reduced glutathione (GSH) yielded monomethylarsonous acid (MMA), dimethylarsinic acid (DMA), and trimethylarsine oxide (TMAO) as products with a methylation rate over 95%. In contrast, when methylcobalamin (CH₃B₁₂) was used as the methyl donor, only MMA and DMA were produced and the methylation rate dropped to around 20%. Reductive demethylation of a methyl-corrinoid coordination complex mediated by GSH is suggested as a mechanism of methyl transfer to arsenic trioxide. The differences observed for different corrinoid coordination complexes with respect to the reactivity of methyl transfer to arsenic is ascribable to differences inherent in the base-on (CH₃B₁₂) and base-off (CH₃B₁₂ ester) natures of the compounds.     

Synthetic studies on the dienophile unit of methyl isosartortuoate. Part 2: SmI2-mediated 14-membered carbocyclization

The dienophile unit of methyl isosartortuoate has been synthesized. The 14-membered carbocycle was constructed by a SmI₂-mediated intramolecular Reformatsky reaction. The introduction of the oxo group at the γ-position of the α,β-unsaturated ester was achieved by rearrangement of an β,γ-epoxy ester.     

Synthesis of 1-fluoroindan-1-carboxylic acid (FICA) and its properties as a chiral derivatizing agent

1-Fluoroindan-1-carboxylic acid (FICA) (1) was designed and synthesized as its methyl ester (FICA Me ester) (4) in order to develop an efficient chiral derivatizing agent (CDA) which excels α-methoxy-α-(trifluoromethyl)phenylacetic acid (MTPA) in capability. FICA Me ester (4) was prepared by fluorination of methyl 1-hydroxyindan-1-carboxylate (3) with (diethylamino)sulfur trifluoride (DAST) and derived to the esters of racemic secondary alcohols by ester exchange reaction. The resulting Δδ_F value was large in the case of 2-butyl ester of FICA (5a), whereas not detectable in the case of the corresponding MTPA ester (6a). The magnitude of the Δδ_H values was similar to that of MTPA esters. The diastereomers of (R)-(−)-8-phenylmenthyl ester of FICA (5i) was separated and their ¹H NMR analyses revealed that the concept of the modified Mosher's method was successfully applied to 5i.     

CeCl3-Catalyzed Reduction of Methyl Esters of Carboxylic Acids to Corresponding Alcohols with Sodium Borohydride

A wide range of methyl esters, including esters of aromatic carboxylic acids, alkenyl carboxylic acids, aliphatic carboxylic acids, and protected amino acids, were reduced to the corresponding alcohols with NaBH₄ in ethanol in the presence of a catalytic amount of CeCl₃. The reaction was completed within 24 h at ambient temperature and showed high functional group compatibility and chemoselectivity. With esters containing nitro, methoxyl, halogen, alkenyl, and protected amino functionalities, only the ester group was reduced. The alcohols were isolated after evaporation of the solvent and routine aqueous workup in good yields (75–95%).     

Michael additions to acrylonitrile,methyl acrylate and methyl vinyl ketone to Nb-benzylidenetryptophan methyl ester

Michael addition to methyl acrylate and methyl vinyl ketone of N_b-benzylidene-L-tryptophan methyl ester 1 gave 2-(3-indolylmethyl)glutamic dimethyl ester 2a and α-(3-oxobutyl)tryptophan methyl ester 2b respectively. Addition to acrylonitrile of 1 yielded α,N_a-dicyanoethyltryptophan methyl ester 3 .     

Normal Phase High Performance Liquid Chromatography of Some Prostaglandin B1 Derivatives

Abstract

15-Keto-13, 14-trans-prostaglandin B₁ methyl ester, 13,14-trans-prostaglandin B₁ methyl ester, 13,14-cis-prostaglandin B₁ methyl ester, 13,14-dihydro-prostaglandin B₁ methyl ester and 13,14-dehydro-prostaglandin B₁ are organic intermediates used in the synthesis of prostaglandin B_x, a polymeric derivative of 15-keto-prostaglandin B₁ methyl ester. PGB_x has been shown to protect laboratory animals against cardiogenic shock, cerebral ischemia and hypoxia. A normal phase, high performance liquid chromatographic analysis is presented which permits the identification and quantitation of these PGB₁ intermediates.     

Transition metal-catalyzed formation of CF3-substituted α,β-unsaturated alkene and the synthesis of α-trifluoromethyl substituted β-amino ester

A new transition metal-catalyzed formation of CF₃-substituted α,β-unsaturated alkenes through the ylide intermediate from the reaction between methyl 3,3,3-trifluoro-2-diazopropionate 1 and aryl aldehydes has been developed. Further transformation of the alkene affords the α-trifluoromethyl substituted β-amino ester, a valuable intermediate in the synthesis of fluorine-containing amino acids with potential biological application.     

1-Aryltetralin privileged structure-based libraries: parallel synthesis of N-aryl and N-biaryl γ-lactam lignans

The parallel solution-phase synthesis of two libraries of product-like compounds derived from a 1-aryltetralin privileged structure is described. The N-aryl picropodophyllone γ-lactams were synthesized from methyl ester thuriferic acid via InCl₃-tandem aza-Michael addition-cyclization reaction of anilines. Bromo-aryl compounds from this library were subjected to a ligandless palladium Suzuki cross-coupling to give the expected N-biaryl picropodophyllin γ-lactams.     

Gas‐Phase Oxidation of Methyl‐10‐undecenoate in a Jet‐Stirred Reactor

To better understand the chemistry of biodiesel surrogates, the gas‐phase oxidation of a C₁₂ unsaturated methyl ester, methyl‐10‐undecenoate, has been studied in a jet‐stirred reactor in the temperature range 500–1100 K. These experiments were performed using neat fuel synthesized in the laboratory, with an initial fuel mole fraction set as 0.0021, at quasi‐atmospheric pressure (1.07 bar), at a residence time of 1.5 s with dilute mixtures in helium of equivalence ratios of 0.5, 1.0, and 2.0. The maximum obtained conversion was shown to be more than twice lower than that of methyl decanoate under the same conditions. This difference cannot be reproduced by the only published model for an unsaturated ester with a close number of carbon atoms (methyl‐9‐decenoate). A large range of products was quantified in addition to common oxidation products: saturated and unsaturated aldehydes, saturated and unsaturated methyl esters with a second carbonyl function, C₂–C₁₀ alkenes, C₄–C₁₀ dienes, C₄–C₁₀ unsaturated methyl esters, C₈–C₉ saturated methyl esters, and saturated, unsaturated, and hydroxyl methyl esters involving a cyclic ether. Pathways of formation for the products specific to unsaturated ester oxidation were proposed, and possible model improvements were discussed.     

Short synthesis of 6-oxoprostaglandin E1 and 6-oxoprostaglandin F1α

6-Oxoprostaglandin E₁ methyl ester was synthesized in a single pot from ($\text{R}$)-4-$\text{t}$-butyldimethylsiloxy-2-cyclopentenone by organocopper conjugate addition with an ω side-chain unit, trapping of the resulting enolate with 6-methoxycarbonyl-2-nitrohex-1-ene, and treatment with aqueous titanium(III) trichloride. Hydrolysis of the methyl ester was accomplished by porcine liver esterase. 6-Oxoprostaglandin F_1α, was obtained from 6-nitroprostaglandin E₁ methyl ester in four steps.     

Mechanism of initiation of methyl methacrylate with lithium tert-alkoxides

An investigation of the solution polymerization of methyl, butyl, isobutyl, sec-butyl, and tert-butyl methacrylates and the polymerization of methyl and butyl methacrylates in the presence of methyl, butyl, and tert-butyl isobutyrate and methyl pivalate showed that the complex order of the initiation reaction with respect to the monomer (about 2) has its cause in the ability of the ester group in the monomer and of methyl or butyl isobutyrate to activate lithium tert-alkoxide. Owing to conjugation, the ester group in the monomer is less active than the ester group in isobutyrate. Steric hindrances of the formation of a complex between lithium tert-alkoxide and ester were also investigated, because this complex is intermediate product necessary for the formation of an activated lithium tert-alkoxide, capable of initiating the polymerization of alkyl methacrylates of the type CH₂?(CH₃)COOCH₂R.     

Response Factor Correction for Estimation of Ester Content in Biodiesel

EN 14103 is generally used for quantification of ester content in biodiesel free of heptadecanoate ester (C17:0) or methyl nonadecanoate (C19:0), which are employed as internal standards. It was observed that ester content obtained by EN 14103 method did not match with theoretical value of biodiesel, as the method did not take care of response factors of each component to compensate for changes in detector sensitivities. In this study, the whole range of fatty acid (C₆–C_24:1) methyl esters have been taken into consideration for the calculation of the ester content. Methyl nonadecanoate (C19:0) was used as an internal standard. The response factors of both the saturated and unsaturated methyl esters in the range C₆–C_24:1 were estimated and found in the range 0.97–1.16. The ester content was calculated after applying the response factors of each methyl ester. The results obtained by this method agreed well with the theoretical value as compared to estimated value using EN14103 method. The results obtained from this method also show good correlation (R ² = 0.98) with ¹H-NMR method. Further, this method does not depend on nature of biodiesel feed stock and is applicable to all methyl biodiesel samples obtained from different raw materials.     

The kinetic method reveals secondary deuterium isotope effects on the proton affinity and gas-phase basicity of glycine and alanine methyl esters

The kinetic method for measuring proton affinities (PA) and gas-phase basicities (GB) was applied to the methyl esters of simple amino acids. The experiments show that the GB and PA values for deuterium labeled glycine methyl ester are indeed greater than that of the corresponding unlabelled glycine methyl ester. The PA of -Ala-OCD₃ is also slightly greater than that of the unlabeled alanine methyl ester. The secondary isotope effects originate, as shown by density functional theory, in differences in zero-point energies and thermal-energy corrections between H and D-bearing molecules.     

NOTE: Synthesis and Characterization of a Poly(acrylamide) with Pendant 1,4-piperazine-2,5-dione Moieties via Post-polymerization Cyclization

A poly(acrylamide) was synthesized from N ^α -Boc-N ^? -acrolyl-l-lysylglycine methyl ester via radical polymerization. This polymer typically had Mn ～ 100,000 g/mol, Mw ～ 300,000 g/mol, and a T_g of 93°C. Removal of Boc with TFA and cyclization with DABCO? in DMSO at 65°C afforded a soluble piperazinedione-containing polymer that had a T_g of 157°C and thermal stability up to 300°C. These results demonstrate a viable and efficient synthetic route to piperazinedione-containing polyacrylamides of high molecular weight. Related polymers that incorporate substituted indane moieties could be useful high T_g materials for fabrication of LC and NLO devices.     

The catalytic role of oxide in the thermooxidative degradation of poly(methyl methacrylate)-TiO2 nanocomposites

The influence of TiO₂ nanoparticles on the thermal degradation of poly(methyl methacrylate) (PMMA) was investigated by TGA. The studied materials were characterized by Py-GC-MS, TEM, SEM, TGA, DSC and TGA-MS. The PMMA-TiO₂ nanocomposites were prepared by melt blending with different (5, 10, 15 and 20 wt% TiO₂) loadings. According to TGA results and to the activation energy (determined by the model-free isoconversional method of Vyazovkin), the incorporation of 5 wt% of TiO₂ nanoparticles into PMMA stabilizes it by more than 40 °C. However, for higher loading contents, a catalytic effect on the thermal decomposition was observed which increased with the oxide content. The results obtained by Py-GC-MS showed clearly that TiO₂ increases the formation of methanol, methacrylic acid and propanoic acid methyl ester during the degradation of PMMA. This catalytic effect could be explained through the interaction of the methoxy group of the methacrylate function with the hydroxyl groups present at the surface of the oxide particles.     

GC-MS Assay For 9α, 15(S)-Dihydroxy-11-Oxo-thromba-5(Z), 13(E)-Dien-1-oic Acid

Abstract

The title compound (TXB₂?M) is a quantitative index of thromboxane A₂ synthesis in the human. We developed a method for its determination in urine based on the use of the ¹³C-labeled methyl ester derivative of the analyte as internal standard and GC-EIMS. the interassay coefficient of variation (CV) was 5.3% (N=4) and the intraassay CV ranged from 2.6 to 8.2% (N=3). the equation of the regression curve correlating the amounts added and recovered was Y=0.932X+3.99 (R=0.9947). the relative recovery of TXB₂?M from nine urine specimens was 99.8 ± 2.8% (mean ± SEM). the mean (±SD) 24-hr output in six healthy male subjects was 1371 ± 307 ng, and in six females it was 1176 ± 418 ng. Concentrations as low as 200 pg/ml of urine can easily be measured with this procedure if one uses 50 ml of urine for the analysis.     

Mass spectrometry of natural products: VIII—Mass spectrometric studies of ring a saturated gibberellins

The fragmentation behaviour of gibberellin A₁ methyl ester and gibberellin C methyl ester has been studied by means of positive and negative ion mass spectrometry, high resolution techniques and metastable ion transitions. The results obtained allow a mass spectrometric distinction to be made between both structural types.     

On the mechanism of isomerization reactions in the esters of some simple α,β-unsaturated carboxylic acids

It is shown from a detailed examination of first field free region metastable peak shapes that the molecular ion of the methyl ester of acrylic acid rearranges into 2- and 3-butenoic acid ions prior to metastable fragmentations involving the losses of H₂O, CH₃˙ and CO. The key intermediate ion in this ester-acid isomerization is shown to be the enol form of ionized γ-butyrolactone. The C-5 homologues methylmethacrylate and ethylacrylate display a similar mechanism for H₂O loss, but the loss of CH₃˙ shows additional mechanistic complexities. It was shown from the metastable peak shapes of ¹³C and deuterium labelled compounds that the larger part of the methyl loss does not occur from acid type ions, but directly from methyl substituted enol ions of γ-butyrolactone. The mechanistic proposals also account for the presence of a pronounced loss of CH₃˙ from the isomeric ester methylcrotonate and the absence of H₂O loss in both methylcrotonate and the methyl ester of 3-butenoic acid.     

Synthesis of gibberellins A8 and A56 from gibberellin A3

A mixture of gibberellin A₃ derivatives with 1(10)-ene-2β,3β-diol and 1(10)-ene-2α,3β-diol (2:5) groups, readily obtained from gibberellin A₃, has been used for a new and simple synthesis of gibberellin A₈ and its esters. The hydrolysis of GA₃ and the iodolactonization of a mixture of the 2-epimers was carried out in aqueous solution in a single flask, as also was a synthesis of GA₅₆ from GA₃ by a method that we have modified. The mixture of 1β-iodides of GA₈ and GA₅₆ was separated by chromatography on SiO₂ in the form of methyl or p-bromophenacyl esters which were then deiodinated and the methyl or p-bromphenacyl ester of GA₈ was isolated. Free GA₈ was obtained by the dephenylation of the latter ester. By two-dimensional NMR spectroscopy we succeeded in assigning all the signals in the¹³C and¹H NMR spectra of the methyl esters of GA₈ and GA₅₆. In an attempt to obtain GA₅ methyl ester by the action of trimethylchlorosilane/sodium iodide on the 2α,3β-diol system in GA₅₆ methyl ester, the 8,13-epimer of the latter was formed, the structure of its molecule being established from the results of X-ray structural analysis.     

Methyl 2,6‐dicarboxybenzoate

Regioselective methyl­ation of hemimellitic acid in basic MeOH yields the title 2‐methyl ester, C₁₀H₈O₆, of the parent acid. The asymmetric unit contains one complete mol­ecule, which packs with the methyl ester groups lying between zigzag chains produced by hydrogen bonding, utilizing the head‐to‐tail carboxylic acid–acid dimer motif.