Biotransformation of nerol by larvae of the common cutworm (Spodoptera litura) was investigated. The resulting major metabolites were (2Z,6E)-1-hydroxy-3,7-dimethyl-2,6-octadien-8-oic acid and 8-hydroxynerol, and the minor metabolites were 9-hydroxynerol and (2Z,6E)-1-hydroxy-3,7-dimethyl-2,6-octadien-8-al. (2Z,6E)-1-Hydroxy-3,7-dimethyl-2,6-octadien-8-oic acid is a novel compound. The results indicate that biotransformation of nerol by S. litura larvae involved 2 pathways; the main pathway involved oxidation at the methyl group of the geminal dimethyl at C-8 position followed by carboxylation, and the minor pathway involved oxidation at the methyl group of the geminal dimethyl at C-9 position.
The biotransformation of geraniol, nerol and citral by Aspergillus niger was studied. A comparison was made between submerged liquid, sporulated surface cultures and spore suspensions. This bioconversion was also carried out with surface cultures of Penicillium sp. The main bioconversion products obtained from geraniol and nerol by liquid cultures of A. niger were linalool and alpha-terpineol. Linalool, alpha-terpineol and limonene were the main products obtained from nerol and citral by sporulated surface cultures, whereas geraniol was converted predominantly to linalool, also resulting in higher yields. Bioconversion of nerol with Penicillium chrysogenum yielded mainly alpha-terpineol and some unidentified compounds. With P. rugulosum the major bioconversion product from nerol and citral was linalool. The bioconversion of nerol to alpha-terpineol and linalool by spore suspensions of A. niger was also investigated. Finally the biotransformation with sporulated surface cultures was also monitored by solid phase microextraction (SPME). It was found that SPME is a very fast and efficient screening technique for biotransformation experiments.
Allylic alcohols, such as geraniol 1, are easily oxidized by varying mechanisms, including the formation of both 2,3-epoxides and/or aldehydes. These epoxides, aldehydes, and epoxy-aldehydes can be interconverted to each other, and the reactivity of them all must be considered when considering the sensitization potential of the parent allylic alcohol. An in-depth study of the possible metabolites and autoxidation products of allylic alcohols is described, covering the formation, interconversion, reactivity, and sensitizing potential thereof, using a combination of in vivo, in vitro, in chemico, and in silico methods. This multimodal study, using the integration of diverse techniques to investigate the sensitization potential of a molecule, allows the identification of potential candidate(s) for the true culprit(s) in allergic responses to allylic alcohols. Overall, the sensitization potential of the investigated epoxyalcohols and unsaturated alcohols was found to derive from metabolic oxidation to the more potent aldehyde where possible. Where this is less likely, the compound remains weakly or nonsensitizing. Metabolic activation of a double bond to form a nonconjugated, nonterminal epoxide moiety is not enough to turn a nonsensitizing alcohol into a sensitizer, as such epoxides have low reactivity and low sensitizing potency. In addition, even an allylic 2,3-epoxide moiety is not necessarily a potent sensitizer, as shown for 2, where formation of the epoxide weakens the sensitization potential. /Geraniol/
IDENTIFICATION AND USE: Nerol is a colorless oily fluid. Nerol is reported to be found in neroli oil (with geraniol) and in many essential oils. It used as a base for the manufacture of perfumes and in fragrances. HUMAN EXPOSURE AND TOXICITY: A single sensitization test was carried out on 25 volunteers. The material was tested at a concentration of 4% in petrolatum and produced no sensitization reactions. In other study, nerol was utilized in a closed patch test on the back or forearm of 314 subjects for 24-48 hr. Slight erythema was demonstrated in 10 (3.19%) subjects. In an in vitro chromosome aberration test in cultured human lymphocytes nerol was not clastogenic with and without metabolic activation. ANIMAL STUDIES: Eye irritant effects were observed in rabbits. Slight skin irritation was observed in guinea pigs and rabbits. Respiratory irritation was assessed in mice by recording their respiratory rate when exposed to nerol. Mice were exposed to the test material for 1 min using a nebulizer for aerosolization in a 2600 mL chamber. Mild to moderate decrease in the respiratory rate was observed, and the ED25 (dose at which there is a 25% reduction in the respiratory rate) was calculated to be 591 ug /L. Rats (10 males/dose) were administered the test substance at 2560 - 9800 mg/kg and observed for 14 days. The numbers of deaths per dose were 1, 4, 7 and 10 at 2560, 4000, 6250 and 9800 mg/kg-bw, respectively. All deaths occurred within two days of dose administration. Clinical signs in rats included exophthalmia, hyperflexiveness, restlessness, lethargy and loss of righting reflex. Nerol was not mutagenic in Salmonella typhimurium (TA 1535, TA 1537, TA 98, TA 100 and TA 102) with or without activation. In an in vitro mammalian cell gene mutation test with mouse lymphoma cells nerol was not mutagenic at the hprt locus of L5178Y mouse lymphoma cells, in the presence and absence of metabolic activation.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
神经毒素 - 急性溶剂综合症
Neurotoxin - Acute solvent syndrome
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
Oral carcinogenesis, a multistep process with multifaceted etiology, arises due to accumulation of heterogeneous genetic changes in the genes involved in the basic cellular functions including cell division, differentiation, and cell death. These genetic changes in the affected cell progressively increase the cell proliferation, angiogenesis, and inhibition of apoptosis. The present study investigated the modulating effect of geraniol on the expression pattern of cell proliferative (PCNA, cyclin D1, c-fos), inflammatory (NF-kappaB, COX-2), apoptotic (p53, Bax, Bcl-2, caspase-3 and -9), and angiogenic (VEGF) markers in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Topical application of 0.5 % DMBA in liquid paraffin, three times a week, for 14 weeks, developed well-differentiated squamous cell carcinoma (SCC) in the buccal pouch of golden Syrian hamsters. All the hamsters treated with DMBA alone (100 %) developed oral tumors in the buccal pouch after 14 weeks. Over-expression of mutant p53, PCNA, Bcl-2, and VEGF accompanied by decreased expression of Bax were noticed in hamsters treated with DMBA alone. Increased expression of c-fos, COX-2, NF-kappaB, and cyclin D1 and decreased activities of caspase-3 and -9 were also noticed in hamsters treated with DMBA alone. Oral administration of geraniol at a dose of 250 mg/kg bw (body weight) not only completely prevented the formation of oral tumors but also prevented the deregulation in the expression of above mentioned molecular markers in hamsters treated with DMBA. The present results thus suggest that geraniol has potent anti-inflammatory, anti-angiogenic, anti-cell proliferative, and apoptosis-inducing properties in DMBA-induced hamster buccal pouch carcinogenesis. /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 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-a, 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. /Geraniol/
In the recent past, several phytoconstituents are being explored for their potential neuromodulatory effects in neurological diseases. Repeated exposure of acrylamide (ACR) leads to varying degree of neuronal damage in experimental animals and humans. In view of this, the present study investigated the efficacy of geraniol (GE, a natural monoterpene) to mitigate acrylamide (ACR)-induced oxidative stress, mitochondrial dysfunction and neurotoxicity in a rat model and compared its efficacy to that of curcumin (CU, a spice active principle with multiple biological activities). ACR administration (50mg/kg bw, i.p. 3times/week) for 4weeks to growing rats caused typical symptoms of neuropathy. ACR rats provided with daily oral supplements of phytoconstituents (GE: 100mg/kg bw/d; CU: 50mg/kg bw/d, 4weeks) exhibited marked improvement in behavioral tests. Both phytoconstituents markedly attenuated ACR-induced oxidative stress as evidenced by the diminished levels of reactive oxygen species, malondialdehyde and nitric oxide and restored the reduced glutathione levels in sciatic nerve (SN) and brain regions (cortex - Ct, cerebellum - Cb). Further, both phytoconstituents effectively diminished ACR-induced elevation in cytosolic calcium levels in SN and Cb. Furthermore, diminution in the levels of oxidative markers in the mitochondria was associated with elevation in the activities of antioxidant enzymes. While ACR mediated elevation in the acetylcholinesterase activity was reduced by both actives, the depletion in dopamine levels was restored only by CU in brain regions. Taken together our findings for the first time demonstrate that the neuromodulatory propensity of GE is indeed comparable to that of CU and may be exploited as a therapeutic adjuvant in the management of varied human neuropathy conditions. /Geraniol/
As a part of corresponding study on the effects of test material on the motility of mice (groups of four 4- to 6-week old and 6-month-old female outbred Swiss mice), concentrations of test material in blood samples were determined after inhalation exposure. Air was passed into the cage through a glass tube containing 1.5 mL of test material for a total test material volume of 20-50 mg. Blood samples were taken from the animals after 0, 30, 60 and 90 minutes of inhalation exposure. The concentration of nerol in blood sample 1 hr following inhalation was 5.7 ng/mL.
Sesquiterpene Cyclizations inside the Hexameric Resorcinarene Capsule: Total Synthesis of δ‐Selinene and Mechanistic Studies
作者：Qi Zhang、Konrad Tiefenbacher
DOI：10.1002/anie.201906753
日期：2019.9.2
capsule was utilized as an artificial cyclase to catalyze the cyclization of sesquiterpenes. With the cyclization reaction as the key step, the first total synthesis of the sesquiterpene natural product δ-selinene was achieved. This represents the first total synthesis of a sesquiterpene natural product that is based on the cyclization of a linear terpene precursor inside a supramolecular catalyst
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.
Bismuth Oxide Perchlorate as a Highly Efficient Catalyst for Heteroatom Acylation Under Solvent-Free Conditions
作者：Asit K. Chakraborti、Rajesh Gulhane、Shivani
DOI：10.1055/s-2003-41442
日期：——
Bismuth oxide perchlorate efficiently catalyzes the acetylation of structurally diverse phenols, alcohols, thiols, and amines undersolventfree conditions. Sterically hindered and electron deficient phenols are acetylated in excellent yields with stoichiometric amounts of Ac 2 O at room temperature. Acylation of acid-sensitive alcohols is carried out efficiently without competitive side reactions
高氯酸铋在无溶剂条件下有效催化结构不同的酚、醇、硫醇和胺的乙酰化。空间位阻和缺电子酚在室温下用化学计量的 Ac 2 O 以极好的收率乙酰化。酸敏感醇的酰化可以有效地进行，没有竞争性副反应。光学活性底物被乙酰化，对光学纯度没有任何不利影响。
Zirconium(IV) Chloride as a New, Highly Efficient, and Reusable Catalyst for Acetylation of Phenols, Thiols, Amines, and Alcohols under Solvent-Free Conditions
作者：Asit K. Chakraborti、Rajesh Gulhane
DOI：10.1055/s-2004-815442
日期：——
chloride has been found to be a new. highly efficient, and reusable catalyst for acetylation of structurally diverse phenols, thiols, amines and alcoholsundersolvent-free condtions. Acetylation of sterically hindered and electron deficient phenols is achieved in excellent yields with stoichiometric amounts of Ac 2 O at room temperature. Acid-sensitive alcohols undergo acetylation with excellent chemoselectivity
已发现氯化锆 (IV) 是一种新的。一种高效、可重复使用的催化剂，用于在无溶剂条件下对结构不同的酚、硫醇、胺和醇进行乙酰化。在室温下使用化学计量量的 Ac 2 O 以极好的收率实现空间位阻和缺电子酚的乙酰化。酸敏感醇以优异的化学选择性进行乙酰化，而不会发生脱水或重排等竞争性副反应。催化剂的温和路易斯酸性质使乙酰化能够与光学活性底物一起进行，而不会对光学纯度产生任何不利影响。
Fluoroboric acid adsorbed on silica gel as a new and efficient catalyst for acylation of phenols, thiols, alcohols, and amines
作者：Asit K. Chakraborti、Rajesh Gulhane
DOI：10.1016/s0040-4039(03)00683-x
日期：2003.4
Fluoroboric acid supported on silica gel efficiently catalyzes acylation of structurally diverse phenols, alcohols, thiols, and amines undersolventfree conditions. Acid-sensitive alcohols are smoothly acylated without competitive side reactions.
