Allyl alcohol is metabolized by alcohol dehydrogenase to acrolein; it is also converted to malondialdehyde. ... The characteristic periportal liver necrosis produced by exposure to allyl alcohol is preceded by rapid depletion of intracellular glutathione. This glutathione depletion is a prerequisite for the production of allyl alcohol-induced toxicity as evidenced by the administration of N-acetylcysteine and other sulfur-containing metabolic precursors of glutathione which prevent allyl alcohol and acrolein-induced hepatotoxicity in cultured cells and in intact animals. ...
The biotransformation of allyl alcohol was studied in rat liver and lung preparation. Acrylic acid was formed from allyl alcohol. Lung and liver microsomal epoxidation products were also identified.
Rates of allyl alcohol metabolism in periportal and pericentral regions of the liver lobule were measured to determine whether the zonal toxicity due to allyl alcohol results from its selective metabolism in periportal regions. Infusion of allyl alcohol into perfused livers from fed, phenobarbital-treated rats caused an increase in nicotinamide adenine dinucleotide, reduced form (NADH) fluorescence (366 leads to 450 nm) measured with a large-tipped (2 mm) light guide placed on the surface of the liver. A linear increase in NADH fluorescence was observed when 25-150 uM allyl alcohol was infused; however, when allyl alcohol exceeded 200 uM, oxygen uptake by the liver was inhibited 30-40%, and a large increase in NADH fluorescence occurred. /4-Methylpyrazole (80 umol), an inhibitor of alcohol dehydrogenase, prevented the fluorescence increased due to allyl alcohol in both regions, indicating that the changes were due entirely to NADH generated from alcohol dehydrogenase-dependent allyl alcohol metabolism./ Using the correlation (r= 0.91) between rates of allyl alcohol uptake and the increase in NADH fluorescence established for the whole organ, local rates of allyl alcohol metabolism were 23 and 31 umoles/g/hr in periportal and pericentral regions, respectively. Since allyl alcohol is metabolized in both regions of the liver lobule, the hypothesis that the zone specific hepatotoxicity results from its exclusive metabolism to acrolein in periportal regions seems unlikely.
In rats, allyl alcohol is metabolized to acrolein by alcohol dehydrogenase. ...Acrolein can react with glutathione to form the corresponding thiol ether, which can be further metabolized to mercapturic acids and excreted in the urine. In the presence of NADPH and liver and lung microsomes, allyl alcohol and acrolein were oxidized to the corresponding epoxides, glycidol, and glycidaldehyde, respectively.
IDENTIFICATION AND USE: Allyl alcohol (AA) is a colorless, mobile liquid. Allyl alcohol is used as an intermediate in the pharmaceutical industry. AA is employed in the production of glycerol, diallyl phthalate, diallyl isophthalate, and in the manufacture of acrolein. It has been used as a denaturant for ethanol, a herbicide for ornamentals, celery beds, and soil treatment in uncultivated areas, as a fungicide for tobacco and grass seed, and as a military warfare gas. Its historical use as an insecticide has been abandoned in the United States. HUMAN STUDIES: Absorption through the skin leads to deep muscle pain, presumably due to spasm. AA can produce dermatitis of variable types and degrees results, in addition to first and second-degree burns with vesiculation. Lacrimation, retrobulbar pain, photophobia, and blurring of vision may be associated with exposure to vapors, and corneal injury has been described resulting in temporary blindness. At least three cases of accidental poisoning have been described following acute inhalation exposures to unknown concentrations of allyl alcohol. In each case, these individuals recovered without sequelae. However, oral ingestion of allyl alcohol by a 55-yr-old man resulted in death within 100 min. The concentration of acrolein in blood was 7.2 mg/L. Death was attributed to acrolein-induced acute cardiotoxicity, similar to that previously documented in animal experiments. At least three cases of accidental poisoning have been described following acute inhalation exposures to unknown concentrations of allyl alcohol. In each case, these individuals recovered without sequelae. ANIMAL STUDIES: Animal studies demonstrate AA appears to be oxidized readily in the liver, giving a variety of metabolic products, such as acrolein, acrylic acid, glycidaldehyde, and glyceraldehyde. Among these metabolites, the most reactive metabolite, acrolein may cause hepatotoxicity in the liver. Rats are significantly more sensitive to allyl alcohol-induced liver damage than mice, an effect due to the three-fold greater biotransformation of allyl alcohol to acrolein and acrylic acid in rats than in mice. Middle-aged and older animals are more susceptible to allyl alcohol-induced hepatotoxicity than are young animals. AA was slightly irritating to the skin and caused severe corneal necrosis when applied to the eyes of animals. AA was not a skin sensitizer in guinea pigs. In a repeat dose inhalation toxicity study, male rats were exposed to AA at concentrations of 0, 2.4, 4.7, 12, 47, 95, 142, 237 or 355 mg/cu m for 7 hours/day, 5 days/week for 12 weeks. Histopathology showed that there was slight congestion of the lungs and liver at the dose of 355 mg/cu m. In a repeated dose oral toxicity study, AA had adverse effects on kidney tissues in rats, administered in the drinking water continuously for 15 weeks at or above a level of 100 ppm. A carcinogenicity study was conducted with male and female rats via drinking water (300 mg/L, total dose of 3.2 g) for 106 weeks, followed by observation until natural death (123-132 weeks). The study gave no clear evidence of carcinogenicity in male rats, but there was equivocal evidence of carcinogenicity in the liver of female rats. The in vitro studies, including reverse mutation assays in bacteria (Salmonella typhimurium: positive in T1535 with S9, TA100 without metabolic activation; negative in TA97, TA98, TA100 and TA1535 without metabolic activation), microbial forward mutation and fungal point mutation assays (Streptomyces coelicolor and Aspergillus nidulans, respectively: negative) and gene mutation in mammalian cells (V79 cells: positive) gave conflicting results, while the in vivo studies concerning micronucleus and the dominant lethal assay in rodents gave negative results. Based on these data, there is equivocal evidence that AA may be genotoxic. Litters sired by male rats treated with a dose of 0.86% allyl alcohol 7 days/wk to week 12 and 5 days/wk from week 13 to 33 did not develop any malformations. No adverse reproductive effects were observed. ECOTOXICITY STUDIES: AA was not toxic to fish embryos, or fish cell lines because it needs to be metabolically activated. AA is highly phytotoxic.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A4；不可归类为人类致癌物。
A4; Not classifiable as a human carcinogen.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
暴露途径
该物质可以通过吸入其蒸汽、通过皮肤接触以及摄入进入人体。
The substance can be absorbed into the body by inhalation of its vapour, through the skin and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
... A single oral intubation of 120 mg/kg allyl alcohol in male Long-Evans rats produced circulating concentrations of 9 to 15 ug/mI at 15 to 120 minutes after exposure. Peak blood concentrations were achieved at 30 to 60 minutes. Following intravenous injection of 30 mg/kg body weight in rats, the parent alcohol was cleared rapidly from the circulation such that within 60 minutes it could no longer be detected in blood. /It was/ concluded that the rate of allyl alcohol metabolism in rats was far slower than that of ethanol.
Allyl alcohol is apparently oxidized readily since within few min after iv injection of rats with the dosage of 30 mg/kg, vena cava blood contained average concentration of about 24 ug/mL; within 15 min concentration was about 4 ug/mL and within 1 hr the alcohol had almost disappeared from the blood. During constant iv infusion the allyl alcohol disappeared at rate of about 23 mg/hr. During the period of 15-120 min after admin of single oral dose of allyl alcohol (120 mg/kg) to rats, mean concentration of this alcohol in the portal vein was between 9 and 15 ug/mL.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
通过完好无损的皮肤吸收，浓度可能达到有毒甚至致命。
...Absorbed through intact skin in toxic and even lethal concentrations.
The breath of eight male volunteer subjects was analyzed to determine the levels of trace organic compounds in the respired air. 2-Propen-1-ol was found at 0.52 and 9.5 ug/hr in expired air from one subject that was a smoker and from one non-smoking subject, respectively. 2-Propen-1-ol was not found in the breath of the other 6 subjects. 2-Propen-1-ol was categorized as a chemical that is thought to result from or be related to normal human metabolism.
Synthesis and biological activity of novel 1β-Methylcarbapenems with oxyiminopyrrolidinylamide moiety
摘要：
The synthesis and antibacterial activity of novel 1beta-methylcarbapenems 1a-f bearing oxyiminopyrrolidinylamide moiety at C-5 position of pyrrolidine are described. Most compounds exhibited comparable antibacterial activity to meropenem against a wide range of Gram-positive and Gram-negative organisms including Pseudomonas aeruginosa isolates. Of these carbapenems, 1a showed potent and broad spectrum of antibacterial activity and similar stability to DHP-I to meropenem. Against clinical isolates of 40 Gram-negative bacterial species including MDR and ESBL-producing strains, the selected carbapenem 1a possessed excellent in vitro activity except for MDR P. aeruginosa, and was comparable in potency to meropenem. (C) 2003 Elsevier Ltd. All rights reserved.
The scope of MgI2 as a valuable tool for quantitative and mild chemoselective cleavage of protectinggroups is described here. This novel synthetic approach expands the use of protectinggroups, widens the concept of orthogonality in synthetic processes, and offers a facile opportunity to release compounds from solid supports.
One-pot synthesis of carbamates and thiocarbamates from Boc-protected amines
作者：Hee-Kwon Kim、Anna Lee
DOI：10.1016/j.tetlet.2016.09.038
日期：2016.11
A highly efficient one-pot procedure for the synthesis of carbamates and thiocarbamates has been described. In the presence of 2-chloropyridine and trifluoromethanesulfonyl anhydride, the isocyanate intermediates were generated in situ for further reactions with alcohols and thiols to afford the desired carbamates and thiocarbamates in high yields.
Fast Ruthenium-Catalysed Allylation of Thiols by Using Allyl Alcohols as Substrates
作者：Alexey B. Zaitsev、Helen F. Caldwell、Paul S. Pregosin、Luis F. Veiros
DOI：10.1002/chem.200900192
日期：2009.6.22
Green and fast: Allylation of aromatic and aliphatic thiols, by usingallylalcohols as substrates, requires only minutes at ambient temperature with a Ru catalyst (see scheme). Quantitative conversion is normal and the catalyst possesses high functional‐group tolerance.
[EN] AURORA KINASE MODULATORS AND METHOD OF USE<br/>[FR] MODULATEURS D'AURORA KINASE ET PROCÉDÉ D'UTILISATION
申请人：AMGEN INC
公开号：WO2009117157A1
公开（公告）日：2009-09-24
The present invention relates to chemical compounds having a general formula (I) wherein A1-5 and 7-8, D', L1, L2, R1, R3, R6-8, n and o are defined herein, and synthetic intermediates, which are capable of modulating the activity of Aurora kinase proteins and, thereby, influencing various disease states and conditions related to the activities of Aurora kinases. For example, the compounds are capable of influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of Aurora kinase.
2-C<i>-</i>Branched Glycosides from 2‘-Carbonylalkyl 2-<i>O-</i>Ms(Ts)-<i>C-</i>Glycosides. A Tandem S<sub>N</sub>2−S<sub>N</sub>2 Reaction via 1,2-Cyclopropanated Sugars
作者：Huawu Shao、Sanchai Ekthawatchai、Shih-Hsiung Wu、Wei Zou
DOI：10.1021/ol0486627
日期：2004.9.1
[reaction: see text] Under basic conditions, 2'-aldehydo (acetonyl) 2-O-Ms(Ts)-alpha-C-glycosides undergo an intramolecular S(N)2reaction to form 1,2-cyclopropanated sugars, which react with nucleophiles (alcohols, thiols, and azide) at the anomeric carbon to give 2-C-branched glycosides. By way of contrast, the 1,2-cyclopropanes derived from2'-ketones only react with thiols to give 2-C-branched
