Metabolites isolated from the urine of rats after oral administration of geraniol (I) were: geranic acid (II), 3-hydroxy-citronellic acid (III), 8-hydroxy-geraniol (IV), 8-carboxy-geraniol (V) and Hildebrandt acid (VI). Metabolites isolated from urine of rats after oral administration of linalool (VII) were 8-hydroxy-linalool (VIII) and 8-carboxy-linalool (IX). After three days of feeding rats with either geraniol or linalool, liver-microsomal cytochrome P-450 was increased. Both NADH- and NADPH-cytochrome c reductase activities were not significantly changed during the six days of treatment. Oral administration of these two terpenoids did not affect any of the lung-microsomal parameters measured.
The fragrance compound geraniol is susceptible to autoxidation when in contact with air, and to cutaneous metabolism. In both processes, the isomeric aldehydes geranial and neral are formed. ...
Male IISc rats were given (1-(3)H)geraniol in daily doses of 800 mg/kg bw by gavage for 20 consecutive days. Five urinary metabolites were identified via two primary pathways. In one pathway, the alcohol is oxidized to yield geranic acid (3,7-dimethyl-2,6-octadienoic acid) which is subsequently hydrated to yield 3, 7-dimethyl-3-hydroxy-6-octenoic acid (3-hydroxy citronellic acid). In a second pathway, the alcohol undergoes selective omega-oxidation of the C8-methyl to yield 8-hydroxygeraniol and 8-carboxygeraniol, the latter of which undergoes further oxidation to the principal urinary metabolite 2,6-dimethyl-2,6-octadienedioic acid (Hildebrandt acid) ... . It was demonstrated that administration of geraniol at a dose of 600 mg/kg bw by gavage for 1, 3 or 6 days induced expression of rat liver microsomal cytochrome P450 and geraniol hydroxylation, but not the activities of rat liver microsomal cytochrome b5, NADPH-cytochrome c reductase, and NADH-cytochrome c reductase, nor the activities of these enzymes in rat lung microsomes ... . Rabbits are also capable of omega-oxidation of geraniol, as both the Hildebrandt acid and its dihydro form (2,6-dimethyl-2-octendioic acid; reduced or dihydro-Hildebrandt acid) were isolated from the urine of treated animals... . In both rabbits and rats, the omega-hydroxylation is mediated by the cytochrome P450 system and requires NADPH and oxygen ... . It has been demonstrated that not only rat liver microsomes are capable of omega-hydroxylating geraniol, but also rat lung and kidney microsomes
来源:Hazardous Substances Data Bank (HSDB)
代谢
香叶醇在人体内的已知代谢物包括[(2E)-3,7-二甲基辛-2,6-二烯基]硫酸氢盐。
Geraniol has known human metabolites that include [(2E)-3,7-Dimethylocta-2,6-dienyl] hydrogen sulfate.
IDENTIFICATION AND USE: Geraniol is colorless to pale-yellow, liquid oil. It has a sweet rose like odor. Geraniol is one of the most frequently used terpenoid fragrance materials. It can be used in all flowery-rose like compositions and does not discolor soaps. In flavor compositions, geraniol is used in small quantities to accentuate citrus notes. It is also used in alcoholic and nonalcoholic beverages, baked goods, chewing gum, frozen dairy, gelatin (pudding), gravies, hard candy, meat products, soft candy. It is an important intermediate in the manufacture of geranyl esters, citronellol, and citral. HUMAN EXPOSURE AND TOXICITY: A report of a 32 year old female patient working in a company for baking ingredients, who had been handling grated lemon peel and lemon oil for several years, developed allergic contact dermatitis of the fingers of both her hands. The material responsible for the dermatitis was identified as geraniol in both lemon peel and lemon oil and it proved to be the only source of the allergic reaction. In a human patch test, geraniol at a 32% concentration was severely irritating and geranyl acetate mildly irritating. Occupational exposure to geraniol may occur through inhalation and dermal contact with this compound at workplaces where geraniol is produced or used. Monitoring data indicate that the general population may be exposed to geraniol by inhalation through use of consumer products, ingestion of food, and dermal contact with this compound and other consumer products containing geraniol. Single compounds (SC) of fragrance mix (FM) contribute differently to FM patch test reactions. The data collected by the Information Networks of the Departments of Dermatology multicenter project from 1996-2002 were analyzed. SCs were tested in a selected group of patients, ranging from n=1083 to n=1924 per year. Reactions to SCs in FM positive patients were observed in 29% (oak moss absolute) to 5.9% geraniol. There was no time trend in reactions to SC's, although the relative share was increased for isoeugenol, cinnamic aldehyde and geraniol in 1999. ANIMAL STUDIES: Geraniol is described as not irritating in the rabbit acute dermal irritation corrosion test. It was not sensitizing in the guinea pig maximization test. Groups of five male and five female weanling rats were given diets containing geraniol for 16 weeks. No treatment related effects on growth, hematological parameters or organ weights, or on macroscopic or microscopic changes in the tissues were observed. An in vitro chromosomal aberration test was conducted in Chinese hamster fibroblast without metabolic activation. Three doses of geraniol were examined and the results were equivocal. Polyploidization effects were observed. The incidence of chromosomal aberrations at 48 hours was in the range considered negative. ECOTOXICITY STUDIES: Essential oil constituents were tested for their neurophysiological effects in Periplaneta americana cockroach and Blaberus discoidalis cockroach. Geraniol had similar depressive effects but increased spontaneous firing at lower doses. Similar effects occurred in dorsal unpaired median (DUM) neurons, recorded intracellularly in the isolated terminal abdominal ganglion of P. americana.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
对人类不具有致癌性（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity to humans (not listed by IARC).
Neurotoxin - Acute solvent syndrome
Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.
Skin Sensitizer - An agent that can induce an allergic reaction in the skin.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
The fragrance terpene geraniol forms sensitizing compounds via autoxidation and skin metabolism. Geranial and neral, the two isomers of citral, are the major haptens formed in both of these activation pathways. /The objective of the study was/ to investigate whether testing with oxidized geraniol detects more cases of contact allergy than testing with pure geraniol. The pattern of reactions to pure and oxidized geraniol, and metabolites/autoxidation products, was studied to investigate the importance of autoxidation or cutaneous metabolism in contact allergy to geraniol. Pure and oxidized geraniol were tested at 2.0% petrolatum in 2227 and 2179 consecutive patients, respectively. In parallel, geranial, neral and citral were tested in 2152, 1626 and 1055 consecutive patients, respectively. Pure and oxidized geraniol gave positive patch test reactions in 0.13% and 0.55% of the patients, respectively. Eight of 11 patients with positive patch test reactions to oxidized geraniol also reacted to citral or its components. Relevance for the positive patch test reactions in relation to the patients' dermatitis was found in 11 of 14 cases. Testing with oxidized geraniol could detect more cases of contact allergy to geraniol. The reaction pattern of the 14 cases presented indicates that both autoxidation and metabolism could be important in sensitization to geraniol.
Geraniol (GO) potent antitumor and chemopreventive effects are attributed to its antioxidant and anti-inflammatory properties. In the current study, the potential efficacy of GO (250 mg/kg) in ameliorating metabolic syndrome (MetS) induced by fructose in drinking water /administered to rats/ was elucidated. Moreover, the effect of pioglitazone (5 and 10 mg/kg; PIO) and the possible interaction of the co-treatment of GO with PIO5 were studied in the MetS model. After 4 weeks of treatment, GO and/or PIO reduced the fasting blood glucose and the glycemic excursion in the intraperitoneal glucose tolerance test. GO and PIO5/10 restrained visceral adiposity and partly the body weight gain. The decreased level of peroxisome proliferator activated receptor (PPAR)-gamma transcriptional activity in the visceral adipose tissue of MetS rats was increased by single treatment regimens. Though GO did not affect MetS-induced hyperinsulinemia, PIO5/10 lowered it. Additionally, GO and PIO5/10 suppressed glycated hemoglobin and the receptor for advanced glycated end products (RAGE). These single regimens also ameliorated hyperuricemia, the disrupted lipid profile, and the elevated systolic blood pressure evoked by MetS. The rise in serum transaminases, interleukin-1beta, and tumor necrosis factor-alpha, as well as hepatic lipid peroxides and nitric oxide (NO) was lowered by the single treatments to different extents. Moreover, hepatic non-protein thiols, as well as serum NO and adiponectin were enhanced by single regimens. Similar effects were reached by the combination of GO with PIO5; however, a potentiative interaction was noted on fasting serum insulin level, while synergistic effects were reflected as improved insulin sensitivity, as well as reduced RAGE and triglycerides. Therefore, GO via the transcriptional activation of PPAR-gamma reduces inflammation and free radical injury produced by MetS. Thereby, these effects provide novel mechanistic insights on GO management of MetS associated critical risk factors. Moreover, the co-administration of GO to PIO5 exalted the antidiabetic drug anti-MetS efficacy.
The profile of the geraniol concentrations in rat blood following oral administration of the emulsified formulation was characterized by a peak concentration at 30 min of about 270 μg/mL and an area under concentration (AUC) similar to that obtained by the intravenous administration of the same geraniol dose, indicating an absolute bioavailability of 92%. Geraniol appears able to permeate directly from the bloodstream to the central nervous system following its oral administration to rats, reaching detectable amounts in the CSF; peak concentration in the CSF was found to be about 2.5 μg/mL and was observed 30 min after oral administration.
(Hydroxystyryl)dimethylsilyl (HSDMS) and (hydroxystyryl)diisopropylsilyl (HSDIS) reagents have been developed that readily protect primary and secondary alcohols and can be removed on irradiation with short wavelength light in polar solvent.
A Bifunctional Copper Catalyst Enables Ester Reduction with H<sub>2</sub>: Expanding the Reactivity Space of Nucleophilic Copper Hydrides
作者：Birte M. Zimmermann、Trung Tran Ngoc、Dimitrios-Ioannis Tzaras、Trinadh Kaicharla、Johannes F. Teichert
DOI：10.1021/jacs.1c09626
日期：2021.10.13
activation of esters through hydrogen bonding and formation of nucleophilic copper(I) hydrides from H2, resulting in a catalytic hydride transfer to esters. The reduction step is further facilitated by a proton shuttle mediated by the guanidinium subunit. This bifunctional approach to ester reductions for the first time shifts the reactivity of generally considered “soft” copper(I) hydrides to previously
采用基于铜 (I)/NHC 配合物和胍有机催化剂的双功能催化剂，促进了以 H 2作为末端还原剂的催化酯还原成醇。这里采用的方法能够通过氢键同时活化酯，并从 H 2形成亲核的氢化铜 (I) ，从而导致氢化物催化转移到酯。由胍亚基介导的质子穿梭进一步促进了还原步骤。这种酯还原的双功能方法首次将通常认为的“软”氢化铜 (I) 的反应性转变为以前不反应的“硬”酯亲电子试剂，并为用催化剂和 H 2替代化学计量还原剂铺平了道路.
A direct approach to amines with remote stereocentres by enantioselective CuH-catalysed reductive relay hydroamination
作者：Shaolin Zhu、Nootaree Niljianskul、Stephen L. Buchwald
DOI：10.1038/nchem.2418
日期：2016.2
elements in many pharmaceutical agents and natural products. However, previously reported methods to prepare these compounds in an enantioselective manner are indirect and require multistep synthesis. Here, we report a copper-hydride-catalysed, enantioselectivesynthesis of γ- or δ-chiral amines from readily available allylic alcohols, esters and ethers using a reductive relay hydroamination strategy (a
Biomimetic Syntheses of Analogs of Hongoquercin A and B by Late-Stage Derivatization
作者：Thomas Mies、Andrew J. P. White、Philip J. Parsons、Anthony G. M. Barrett
DOI：10.1021/acs.joc.0c02638
日期：2021.1.15
described. The parent enyne resorcylate precursors were synthesized biomimeticallyfrom the corresponding dioxinone keto ester via regioselective acylation, Tsuji-Trost allylic decarboxylative rearrangement, and aromatization. The dioxinone keto ester 12 was prepared in 6 steps from geraniol using allylic functionalization and alkyne synthesis.
Herein, the preparation of neoglycoconjugates bearing mannose-6-phosphate analogues is described by: (a) synthesis of a cyclic sulfate precursor to access the carbohydrate head-group by nucleophilic displacement with an appropriate nucleophile; (b) introduction of spacers on the mannose-6-phosphate analogues via Huisgen’s cycloaddition, the Julia reaction, or the thiol-ene reaction under ultrasound
在本文中，带有 6-磷酸甘露糖类似物的新糖缀合物的制备通过以下方式进行描述：（a）通过用适当的亲核试剂亲核置换来合成环状硫酸盐前体以接近碳水化合物头基；（ b ）通过Huisgen的环加成反应、Julia反应或超声活化下的硫醇-烯反应在6-磷酸甘露糖类似物上引入间隔基。有了所得到的化合物，金纳米粒子可以用各种碳水化合物衍生物（糖缀合物）进行功能化，然后测试血管生成活性。据观察，将糖类似物与纳米颗粒分开的间隔物的长度和柔韧性对生物反应几乎没有影响。
Widely Applicable Hydrofluorination of Alkenes via Bifunctional Activation of Hydrogen Fluoride
作者：Zhichao Lu、Xiaojun Zeng、Gerald B. Hammond、Bo Xu
DOI：10.1021/jacs.7b12704
日期：2017.12.20
Expanding the use of fluorine in pharmaceuticals, agrochemicals and materials requires a widely applicable and more efficient protocol for the preparation of fluorinated compounds. We have developed a new generation nucleophilic fluorination reagent, KHSO4-13HF, HF 68 wt/wt %, that is not only easily handled and inexpensive but also capable of hydrofluorinating diverse, highly functionalized alkenes
