Xi:Irritant;
110-17-8Relevant articles and documents
Production of Plant Phthalate and its Hydrogenated Derivative from Bio-Based Platform Chemicals
Lu, Rui,Lu, Fang,Si, Xiaoqin,Jiang, Huifang,Huang, Qianqian,Yu, Weiqiang,Kong, Xiangtao,Xu, Jie
, p. 1621 - 1627 (2018)
Direct transformation of bio-based platform chemicals into aromatic dicarboxylic acids and their derivatives, which are widely used for the manufacture of polymers, is of significant importance for the sustainable development of the plastics industry. However, limited successful chemical processes have been reported. This study concerns a sustainable route for the production of phthalate and its hydrogenated derivative from bio-based malic acid and erythritol. The key Diels–Alder reaction is applied to build a substituted cyclohexene structure. The dehydration reaction of malic acid affords fumaric acid with 96.6 % yield, which could be used as the dienophile, and 1,3-butadiene generated in situ through erythritol deoxydehydration serves as the diene. Starting from erythritol and dibutyl fumarate, a 74.3 % yield of dibutyl trans-4-cyclohexene-1,2-dicarboxylate is obtained. The palladium-catalyzed dehydrogenation of the cycloadduct gives a 77.8 % yield of dibutyl phthalate. Dibutyl trans-cyclohexane-1,2-dicarboxylate could be formed in nearly 100 % yield under mild conditions by hydrogenation of the cycloadduct. Furthermore, fumaric acid and fumarate, with trans configurations, were found to be better dienophiles for this Diels–Alder reaction than maleic acid and maleate, with cis configuration, based on the experimental and computational results. This new route will pave the way for the production of environmental friendly plastic materials from plants.
An efficient and practical system for the catalytic oxidation of alcohols, aldehydes, and α,β-unsaturated carboxylic acids
Grill, Joseph M.,Ogle, James W.,Miller, Stephen A.
, p. 9291 - 9296 (2006)
(Chemical Equation Presented) Upon exposure to commercial bleach (～5% aqueous sodium hypochlorite), nickel(II) chloride or nickel(II) acetate is transformed quantitatively into an insoluble nickel species, nickel oxide hydroxide. This material consists of high surface area nanoparticles (ca. 4 nm) and is a useful heterogeneous catalyst for the oxidation of many organic compounds. The oxidation of primary alcohols to carboxylic acids, secondary alcohols to ketones, aldehydes to carboxylic acids, and α,β- unsaturated carboxylic acids to epoxy acids is demonstrated using 2.5 mol % of nickel catalyst and commercial bleach as the terminal oxidant. We demonstrate the controlled and selective oxidation of several organic substrates using this system affording 70-95% isolated yields and 90-100% purity. In most cases, the oxidations can be performed without an organic solvent, making this approach attractive as a "greener" alternative to conventional oxidations.
TAN-1323 C and D, new concanamycin-group antibiotics; Detection of the angiostatic activity with a wide range of macrolide antibiotics
Ishii,Hida,Iinuma,Muroi,Nozaki
, p. 12 - 20 (1995)
We detected potent angiostatic activity in a MrOH extract from the mycelia of microbial strain S-45628 in the chick chorioallantoic membrane (CAM) assay. The producer was taxonomically characterized as Streptomyces purpurascens. Active principles designated TAN-1323 A~D were isolated and determined to be 18-membered macrolide antibiotics; components C and D are new members of this group, while components A and B are identical to concansmycins C and A, respectively. When tested in the CAM assay, components B and D gave huge avascular zones at the extremely low doses of 10~100ng/disk, although components A and C showed far weaker activity due to their preferential tissue-damaging effect on the CAM. The discovery that these 18-membered macrolide antibiotics are angiostatic substances prompted us to examine other types of macrolide antibiotics, leading to the discovery that 18-membered macrolide antibiotics such as bafilomycin C1, tylosin and leucomycin also show angiostatic activity on the CAM. Thus, angiostatic potential is widely distributed among macrolide antibiotics. The mechanism of action of these macrolide antibiotics is also discussed.
Potent covalent inhibitors of bacterial urease identified by activity-reactivity profiling
Macegoniuk, Katarzyna,Kowalczyk, Rafa?,Rudzińska, Anna,Psurski, Mateusz,Wietrzyk, Joanna,Berlicki, ?ukasz
, p. 1346 - 1350 (2017)
Covalent enzyme inhibitors constitute a highly important group of biologically active compounds, with numerous drugs available on the market. Although the discovery of inhibitors of urease, a urea hydrolyzing enzyme crucial for the survival of some human pathogens, is a field of medicinal chemistry that has grown in recent years, covalent urease inhibitors have been rarely investigated until now. Forty Michael acceptor-type compounds were screened for their inhibitory activities against bacterial urease, and several structures exhibited high potency in the nanomolar range. The correlation between chemical reactivity towards thiols and inhibitory potency indicated the most valuable compound — acetylenedicarboxylic acid, with Ki?=42.5 nM and logkGSH=-2.14. Molecular modelling studies revealed that acetylenedicarboxylic acid is the first example of highly effective mode of binding based on simultaneous bonding to a cysteine residue and interaction with nickel ions present in the active site. Activity-reactivity profiling of reversible covalent enzyme inhibitors is a general method for the identification of valuable drug candidates.
Purification and characterization of a lyase from the EDTA-degrading bacterial strain DSM 9103 that catalyzes the splitting of [S,S]-ethylenediaminedisuccinate, a structural isomer of EDTA
Witschel, Margarete,Egli, Thomas
, p. 419 - 428 (1997)
The bacterial strain DSM 9103, able to utilize EDTA as a sole source of carbon, nitrogen, and energy, is also capable to grow with [S,S]-ethylenediaminedisuccinate ([S,S]-EDDS), a structural isomer of EDTA. In cell-free extracts of [S,S]-EDDS-grown bacteria, [S,S]-EDDS degradation was observed in the absence of any cofactors. An enzyme was purified 41-fold that catalyzed the non-hydrolytic splitting of [S,S]-EDDS leading to the formation of fumarate and N-(2-aminoethyl) aspartic acid. These data strongly suggest that the enzyme belongs to the group of carbon-nitrogen lyases. The splitting reaction was reversible, and an equilibrium constant of approximately 43.0 10-1 M was determined. Out of the three stereo-isomers of EDDS, [S,S]- and [R,S]-EDDS were accepted as substrates by the lyase, whereas [R,R]-EDDS remained unchanged in assays with both cell-free extracts and pure enzyme. The enzyme catalyzed the transformation of free [S,S]-EDDS and of [S,S]-EDDS-metal complexes with stability constant lower than 10, namely of MgEDDS, CaEDDS, BaEDDS and to a small extent also of MnEDDS; Fe(III)EDDS, NiEDDS, CuEDDS, CoEDDS and ZnEDDS were not transformed.
Structural and kinetic studies on adenylosuccinate lyase from Mycobacterium smegmatis and Mycobacterium tuberculosis provide new insights on the catalytic residues of the enzyme
Banerjee, Sanchari,Agrawal, Monika J.,Mishra, Diptimayee,Sharan, Siddharth,Balaram, Hemalatha,Savithri, Handanhal S.,Murthy, Mathur R. N.
, p. 1642 - 1658 (2014)
Adenylosuccinate lyase (ASL), an enzyme involved in purine biosynthesis, has been recognized as a drug target against microbial infections. In the present study, ASL from Mycobacterium smegmatis (MsASL) and Mycobacterium tuberculosis (MtbASL) were cloned, purified and crystallized. The X-ray crystal structure of MsASL was determined at a resolution of 2.16 A. It is the first report of an apo-ASL structure with a partially ordered active site C3 loop. Diffracting crystals of MtbASL could not be obtained and a model for its structure was derived using MsASL as a template. These structures suggest that His149 and either Lys285 or Ser279 of MsASL are the residues most likely to function as the catalytic acid and base, respectively. Most of the active site residues were found to be conserved, with the exception of Ser148 and Gly319 of MsASL. Ser148 is structurally equivalent to a threonine in most other ASLs. Gly319 is replaced by an arginine residue in most ASLs. The two enzymes were catalytically much less active compared to ASLs from other organisms. Arg319Gly substitution and reduced flexibility of the C3 loop might account for the low catalytic activity of mycobacterial ASLs. The low activity is consistent with the slow growth rate of Mycobacteria and their high GC containing genomes, as well as their dependence on other salvage pathways for the supply of purine nucleotides.
Microflow photochemistry - A reactor comparison study using the photochemical synthesis of terebic acid as a model reaction
Aida, Shin,Terao, Kimitada,Nishiyama, Yasuhiro,Kakiuchi, Kiyomi,Oelgem?ller, Michael
, p. 5578 - 5581 (2012)
The continuous-microflow photochemical synthesis of terebic acid from maleic acid was investigated in two different microreactor set-ups. The results were subsequently compared to analogue experiments in a conventional chamber reactor. Based on conversion rates, reactor design and energy efficiency calculations, the simple microcapillary reactor showed the best overall performance.
Mechanism of the Enzymic Elimination of Ammonia from 3-Substituted Aspartic Acids by 3-Methylaspartase
Botting, Nigel P.,Akhtar, Mahmoud,Cohen, Mark A.,Gani, David
, p. 1371 - 1373 (1987)
Kinetic experiments with 3-methylaspartase, using aspartic, 3-methylaspartic, and 3-ethylaspartic acid and the appropriate C-3 deuteriated isotopomers as substrates, reveal that C(3)-H bond cleavage is partially rate-limiting for 3-methylaspartic acid, much less rate-limiting for 3-ethylaspartic acid, and not rate-limiting at all for aspartic acid.
The 3-methylaspartase reaction probed using 2H- and 15N-Isotope effects for three substrates: A flip from a concerted to a carbocationic amino-enzyme elimination mechanism upon changing the C-3 stereochemistry in the substrate from R to S
Gani, David,Archer, Catherine H.,Botting, Nigel P.,Pollard, John R.
, p. 977 - 990 (1999)
The mechanisms of the elimination of ammonia from (2S,3S)-3-methylaspartic acid, (2S)-aspartic acid and (2S,3R)-3-methylaspartic acid, catalysed by the enzyme l-threo-3-methylaspartase ammonia-lyase (EC 4.3.1.2) have been probed using 15N-isotope effects. The 15N-isotope effects for V/K for both (2S,3S)-3-methylaspartic acid and aspartic acid are 1.0246±0.0013 and 1.0390±0.0031, respectively. The natural substrate, (2S,3S)-3-methylaspartic acid, is eliminated in a concerted fashion such that the C(β)-H and C(α)-N bonds are cleaved in the same transition state. (2S)-Aspartic acid appears to follow the same mechanistic pathway, but deprotonation of the conjugate acid of the base for C-3 is kinetically important and influences the extent of 15N-fractionation. (2S,3R)-3-Methylaspartic acid is deaminated via a stepwise carbocationic mechanism. Here we elaborate on the proposed model for the mechanism of methylaspartase and propose that a change in stereochemistry of the substrate induces a change in the mechanism of ammonia elimination. Copyright (C) 1999 Elsevier Science B.V.
ELIMINATION OF HYDROGEN FLUORIDE FROM FLUORINATED SUCCINIC ACIDS.(II) KINETICS OF DEHYDROFLUORINATION OF FLUORO-, 2,2-DIFLUORO-, MESO- AND DL-2,3-DIFLUORO-, AND TRIFLUOROSUCCINIC ACIDS
Hudlicky, M.,Glass, T. E.
, p. 15 - 28 (1983)
Elimination of hydrogen fluoride from fluorosuccinic acid gave fumaric acid, from 2,2-difluorosuccinic acid, meso- and DL-2,3-difluorosuccinic acid fluorofumaric acid, and dehydrofluorination of trifluorosuccinic acid afforded difluoromaleic acid.Kinetic data based on 1H NMR measurements are presented for temperatures of 60 deg C, 75 deg C and 90 deg C.All the dehydrofluorinations follow second order kinetics.Activation energies for the dehydrofluorination of the above acids were found to be: 19.3, 17.3, 18.8, 17.9 and 18.3 kcal, respectively.Since both diastereomeric 2,3-difluorosuccinic acids give fluorofumaric acid as the only product of dehydrofluorination, one of them (DL) undergoes trans elimination while the other (meso) must undergo cis elimination.
