- Biotransformation of [12C]- and [13C]-tert-amyl methyl ether and tert-amyl alcohol
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tert-Amyl methyl ether (TAME) is intended for use as a gasoline additive to increase oxygen content. Increased oxygen content in gasoline reduces tailpipe emissions of hydrocarbons and carbon monoxide from cars. Due to possible widespread use of TAME, the toxicity of TAME is under investigation. We studied the biotransformation of TAME in rats and one human volunteer after inhalation of 12C- or 13C-labeled TAME. In addition, the biotransformation of [13C]-tert-amyl alcohol was studied in rats after gavage. Urinary metabolites were identified by GC/MS and 13C NMR. Rats (two males and two females) were individually exposed to 2000 ppm [12C]- or [13C]TAME for 6 h, and urine was collected for 48 h. Free and glucuronidated 2-methyl-2,3-butanediol and a glucuronide of tert-amyl alcohol were identified by 13C NMR, GC/MS, and LC/MS/MS as major urinary metabolites on the basis of the relative intensities of the 13C NMR signals. The presence of several minor metabolites was also indicated by 13C NMR; they were identified as tert-amyl alcohol, 2-hydroxy-2- methylbutyric acid, and 3-hydroxy-3-methylbutyric acid. One human volunteer was exposed to an initial concentration of 27 000 ppm [13C]TAME by inhalation for 4 min from a 2 L gas sampling bag, and metabolites of TAME excreted in urine were analyzed by 13C NMR. All TAME metabolites identified in rats were also present in the human urine samples. To study tert-amyl alcohol biotransformation, male rats (n = 3) were treated with 250 mg/kg [13C]-tert-amyl alcohol dissolved in corn oil by garage, and urine was collected for 48 h. 13C NMR of the urine samples showed the presence of metabolites identical to those in the urine of [13C]TAME-treated rats. Our results suggest that TAME is extensively metabolized by rats and humans to tert-amyl alcohol which may be further oxidized to diols and carboxylic acids. These reactions are likely mediated by cytochrome P450-dependent oxidations.
- Amberg, Alexander,Bernauer, Ulrike,Scheutzow, Dieter,Dekant, Wolfgang
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Read Online
- 1. 2 - O-alcohol synthetic method of the compound (by machine translation)
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The invention relates to a 1, 2 - O-alcohol synthetic method of the compound. The synthetic method comprises the following steps: (1) in order to at the end of the olefin as raw materials, potassium persulfate compound salt as the oxidizing agent, inorganic salt as catalyst, water and ketone organic solvent as a reaction solvent, for 30 - 100 °C reaction; (2) reaction after the end of the, 0 - 40 °C adding inorganic alkali, the pH for the reaction system 10 - 14; (3) for 30 - 100 °C continue to reaction, after the end of the reaction, separation and purification, be 1, 2 - O-alcohol compound. The method for synthesis of mild reaction system, the raw material is cheap, the oxidizing agent is environment-friendly, good reaction selectivity, high conversion rate. (by machine translation)
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Paragraph 0039; 0040
(2019/03/17)
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- Total synthesis and absolute configuration of avenolide, extracellular factor in Streptomyces avermitilis
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The first total synthesis of extracellular factor, Avenolide, in Streptomyces avermitilis has been achieved using a convergent approach. The stereogenic centers in two key segments were installed using Sharpless epoxidation and dihydroxylation. This synthetic study allowed the determination of the absolute configuration of avenolide as 4S,10R, and yielded important information on its structure-activity relationship.
- Uchida, Miho,Takamatsu, Satoshi,Arima, Shiho,Miyamoto, Kiyoko T,Kitani, Shigeru,Nihira, Takuya,Ikeda, Haruo,Nagamitsu, Tohru
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experimental part
p. 781 - 787
(2012/06/16)
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- 2,3,5-TRISUBSTITUTED PYRIDINES AS INHIBITORS OF CYCLOOXYGENASE-2
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The invention encompasses the novel compound of Formula (I) as well as a method of treating cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula (I). The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula (I).
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- The absolute configuration of cuauhtemone and related compounds
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The absolute configuration of cuauhtemone, a eudesmane-type sesquiterpene isolated from Pluchea species (Asteraceae), has been revised from 1 to 2 by chemical correlation with (R)-(+)-2-methyl-1,2-butanediol 3 through the naturally occurring 2,3-epoxy-2-methylbutanoate derivative 4. The relative stereochemistry of 4 was confirmed by X-ray diffraction analysis. The obtained data are also useful for reconsideration of the absolute configurations of a relevant group of natural products, which were elucidated according to the stereochemistry of cuauhtemone.
- Torres-Valencia, J. Martin,Quintero-Mogica, Dora L.,Leon, Guadalupe I.,Suarez-Castillo, Oscar R.,Villagomez-Ibarra, J. Roberto,Maldonado, Emma,Cerda-Garcia-Rojas, Carlos M.,Joseph-Nathan, Pedro
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p. 543 - 548
(2007/10/03)
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- 2,3,5-trisubstituted pyridines as inhibitors of cyclooxygenase-2
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The invention encompasses the novel compound of Formula I as well as a method of treating cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula I. STR1 The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
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- Product distributions from the OH radical-induced oxidation of but-1-ene, methyl-substituted but-1-enes and isoprene in NO(x)-free air
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Product distributions resulting from the OH-induced oxidation of but-1-ene, 2-methylbut-1-ene, 3-methylbut-1-ene and isoprene in air were measured in the absence of nitrogen oxides and compared with predictions based on currently accepted oxidation mechanisms. In the case of butenes, the observed distributions of carbonyl compounds, hydroxyketones, hydroxyalkanals and diols were evaluated to obtain probabilities for the initial attack of OH radical on the outer position of the double bond (y = 0.90 ± 0.03 for 2-Me-but-1-ene and y = 0.76 ± 0.05 for both but-1-ene and 3-Me-but-1-ene), for the probability of formation of stable products in the self-reaction of secondary β-hydroxyperoxyl radicals (k(ssb)/k(ss) = 0.29 ± 0.07 for but-1-ene and k(ssb)/k(ss) = 0.19 ± 0.06 for 3-Me-but-1-ene), and for the ratio of the reaction with oxygen vs. decomposition of β-hydroxyalkoxyl radicals, k3[O2]/(k4 + k3[O2]) = 0.25 ± 0.04 for but-1-ene and = 0.38 ± 0.04 for 3-Me-but-1-ene. The last two values disagree with other published data, which suggest a smaller effect of oxygen. The oxidation of isoprene produced methacrolein and methyl vinyl ketone with a ratio 0.93 ± 0.10, the ratio of methyl vinyl ketone and 3-methylfuran was 7.3 ± 1.0. Other products were 1-hydroxy-3-methylbut-3-en-2-one (identified by mass spectrometry) and 3-methyl-3-oxo-butane (tentatively identified). The overall product distribution was complex and could not be fully elucidated. Computer simulations based on several mechanisms applied the relative probabilities for OH addition found for the but-1-enes. Comparison with the experimental data suggests probabilities for OH addition to the methylated double bond of 0.504 ± 0.027 (outer position) and 0.056 ± 0.003 (inner position), and to the non-methylated double bond of 0.335 ± 0.023 (outer position) and 0.105 ± 0.008 (inner position).
- Benkelberg,Boge,Seuwen,Warneck
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p. 4029 - 4039
(2007/10/03)
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- The absolute configuration and total synthesis of korormicin
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The marine antibiotic korormicin, isolated from the culture filtrate of marine bacterial strain Pseudoalteromonas sp. F-420, specifically inhibits the growth of marine Gram-negative bacteria without affecting terrestrial species. The absolute configuration of korormicin was determined by the combination of a CD exciton chirality method and chemical degradation. Convergent total synthesis of korormicin has been also achieved.
- Uehara, Hisatoshi,Oishi, Tohru,Yoshikawa, Kazuhiro,Mochida, Kenichi,Hirama, Masahiro
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p. 8641 - 8645
(2007/10/03)
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- Enantioselective preparation of (2R,3R)-(+)- and (2S,3S)-(-)-2,3-epoxy- 2-methylbutanoic acids and some derivatives
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(2R,3R)-(+)- and (2S,3S)-(-)-2,3-epoxy-2-methylbutanoic acids (epoxyangelic acids) were prepared from (Z)-2-methyl-2-butenoic acid using the Sharpless asymmetric epoxidation method in combination with the use of (- )- and (+)-menthol as chiral auxiliaries. Both substances, obtained in high enantiomeric excess, were characterized by spectroscopic and optical activity data. Their absolute configuration was determined by correlation with (R)- (+)-2-methyl-1,2-butanediol.
- Torres-Valencia, J. Martin,Cerda-Garcia-Rojas, Carlos M.,Joseph-Nathan, Pedro
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p. 757 - 764
(2007/10/03)
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- Preparation of (2R,3S)-(-)- and (2S,3R)-(+)-2,3-Epoxy-2-methylbutanoic Acids and Some of Their Esters
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Enantiomerically pure (2R,3S)-(-)- and (2S,3R)-(+)-2,3-epoxy-2-methylbutanoic acids 7 and 8 were prepared from 2-methyl-2-butenoic acid 1 (tiglic acid).They were characterized by spectroscopic and optical activity data and their absolute configuration was determined by chemical correlation with (R)-(+)- and (S)-(-)-2-methyl-1,2-butanediols.The corresponding methyl (16 and 17), menthyl (3 and 4), and 9α-angeloyloxy-1-oxolongipin-2-en-7β-yl (14 and 15) esters were also prepared.
- Torres-Valencia, J. Martin,Cerda-Garcia-Rojas, Carlos M.,Joseph-Nathan, Pedro
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p. 1611 - 1616
(2007/10/02)
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- Intermediates for preparing optically active carboxylic acids
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A process is described for preparing optically active alpha-arylalkanoic acids consisting of rearranging an optically active ketal of formula STR1 in which the substituents have the meaning given in the description of the invention.
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- α-ALKYLATION OF α-HETEROSUBSTITUTED CARBOXYLIC ACIDS WITHOUT RACEMIZATION; EPC-SYNTHESES OF TERTIARY ALCOHOLS AND THIOLS
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α-Hydroxy- and α-mercapto-carboxylic acids are condensed with pivalaldehyde to give 2-t-butyl-5-substituted-1,3-dioxolanones or 1,3-oxathiolanones (2); the predominate cis-isomers are separeted by crystallization.The cis-disubstituted heterocycles 2 derived from lactic, mandelic and malic acid funish, after deprotonation with LDA, reaction with electrophiles such as alkyl halides, aldehydes and ketones, and hydrolysis α-branched α-hydroxy-carboxylic acids (3, 6, 8, 9, 10).These result from an overall substitution of the proton in the α-CO position with retention of configuration.The optically active carboxylic acids are α-alkylated without racemization and without employment of a chiral auxiliary ("self-reproduction of chirality", Scheme 1).The diastereoselectivities (ds) are generally >95percent (Table 1, 2, and 20-25).
- Seebach, Dieter,Naef, Reto,Calderari, Giorgio
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p. 1313 - 1324
(2007/10/02)
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- Metal-Catalyzed Organic Photoreactions. Titanium(IV) Chloride Catalyzed Photoreaction of Saturated Ketones with Methanol and Its Application to the Synthesis of Frontalin
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Photoreaction of acyclic and cyclic saturated ketones in methanol in the presence of TiCl4 afforded 1,2-diols as the main products.The effect of the substituents on the stereochemical course of the photoreaction was examined with substituted cyclohexanones.Further, the present reaction was applied for the synthesis of a pheromone, frontalin.
- Sato, Tadashi,Kaneko, Hirokazu,Yamaguchi, Shinichi
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p. 3778 - 3782
(2007/10/02)
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