borneol | 1140588-66-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: borneol
• 英文别名: L(-)-borneol；Isoborneol；endo-borneol；(1S)-endo-(-)-borneol；DL-2-Bornanol；(1S,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol
• CAS: 1140588-66-4
• 化学式: C₁₀H₁₈O
• 分子量: 154.252
• InChiKey: DTGKSKDOIYIVQL-NQMVMOMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

毒理性

• 毒性总结

识别和使用：冰片是一种固体。它被用作香料，并作为药物使用，包括传统中医。人类暴露和毒性：冰片不会引起皮肤过敏。其毒性实质上与樟脑相似。人类外周血淋巴细胞在DMSO中暴露于不同浓度的l-冰片，浓度高达600微克/毫升，持续4小时，有和无代谢激活以及24小时无代谢激活。在研究的条件下，l-冰片被认为不具有致裂变性。动物研究：与樟脑类似，实验室动物对冰片的毒性似乎比人类要小得多。冰片增加了大鼠口服处理7天后CYP2D的活性。冰片在小鼠中已被评估其镇痛和抗炎活性。冰片在爪子舔舐的早期和晚期显著减少了痛觉行为，并减少了小鼠的扭动反射。当进行热板测试时，高剂量的冰片产生了痛觉行为的抑制。此外，冰片处理的小鼠减少了角叉菜胶诱导的白细胞迁移到腹腔。冰片的致突变潜力在Ames试验中通过使用鼠伤寒沙门氏菌TA1535、TA1537、TA1538、TA98和TA100菌株，在存在和不存在代谢激活的情况下，用冰片以高达5000微克/平板的浓度处理进行了评估。其他研究证实了在鼠伤寒沙门氏菌TA98和TA100菌株中缺乏致突变潜力。在研究的条件下，冰片被认为在细菌中不具有致突变性。

IDENTIFICATION AND USE: Borneol is a solid. It is used as a flavoring, and as a medication, including traditional Chinese medicine. HUMAN EXPOSURE AND TOXICITY: Borneol does not present a concern for skin sensitization. Toxicity is essentially indistinguishable from that of camphor. Human peripheral blood lymphocytes were exposed to varying concentrations of l-borneol in DMSO up to 600 ug/mL for 4 hr, with and without metabolic activation and 24 hr without metabolic activation. Under the conditions of the study, l-borneol was considered non-clastogenic. ANIMAL STUDIES: As with camphor, laboratory animals appear to be much less susceptible to borneol toxicity than man. Borneol increased the activity of CYP2D in rats orally treated by borneol for 7 days. Borneol has been evaluated for antinociceptive and anti-inflammatory activities in mice. Borneol produced a significant reduction of the nociceptive behavior at the early and late phases of paw licking and reduced the writhing reflex in mice. When the hot plate test was conducted, borneol (in higher dose) produced an inhibition of the nociceptive behavior. Additionally, borneol-treated mice had reduced the carrageenan-induced leukocytes migration to the peritoneal cavity. The mutagenic potential of borneol was assessed in an Ames test with Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98 and TA100 treated with borneol at concentrations up to 5000 ug/ plate in the presence and absence of metabolic activation. Other studies confirming a lack of mutagenic potential in S. typhimurium strains TA98 and TA100 have been published. Under the conditions of the study, borneol is considered not mutagenic in bacteria.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：异冰片是一种白色固体。它被用作食品和饮料中的香料成分。它也用于香水制造和化学酯的制备。人体研究：在一项人体最大量测试中，没有观察到10%异冰片在凡士林中引起的敏感性反应。在0.016%至0.08%的浓度范围内，异冰片对人细胞系测试时没有表现出显著的细胞毒性。动物研究：在0.016%至0.08%的浓度范围内，异冰片对猴细胞系测试时没有表现出显著的细胞毒性。交叉参考化学物质l-冰片和异冰片醋酸酯进行了遗传毒性、重复剂量毒性、发育和生殖毒性的评估。在针对大鼠进行的异冰片醋酸酯13周亚慢性毒性研究中，基于增加的尿细胞排泄，确定无观察到有害效应水平（NOEL）为15 mg/kg/天。在亲代生殖毒性研究中，异冰片醋酸酯的无观察到有害效应水平（NOAEL）确定为300 mg/kg/天。l-冰片在 Ames 测试中不是致突变物。异冰片在 Bluescreen 分析中评估了其遗传毒性潜力，发现在有和没有代谢激活的情况下，异冰片对遗传毒性和细胞毒性均为阴性。

IDENTIFICATION AND USE: Isoborneol is a white solid. It is used as a flavor ingredient in food and beverages. It is also used in perfumery and in preparation of chemical esters.HUMAN STUDIES: In a human maximization test, no reactions indicative of sensitization were observed with 10% isoborneol in petrolatum. Isoborneol did not exhibit significant cytotoxicity at concentrations ranging between 0.016% and 0.08% when tested against human cell lines. ANIMAL STUDIES: Isoborneol did not exhibit significant cytotoxicity at concentrations ranging between 0.016% and 0.08% when tested against monkey cell lines. Read across chemicals l-borneol and isobornyl acetate were evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity. In the13-week subchronic toxicity study for isobornyl acetate conducted in rats the NOEL was determined to be 15 mg/kg/day, based on increased urinary cell excretion.The NOAEL for reproductive toxicity in the parental generation was determined to be 300 mg/kg/day for isobornyl acetate. l-borneol was not mutagenic in the Ames test. Isoborneol, was assessed for genotoxic potential in the Bluescreen assay and was found negative for genotoxicity and cytotoxicity 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 - 其他中枢神经系统神经毒素

Neurotoxin - Other CNS neurotoxin

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素

Neurotoxin - Other CNS neurotoxin

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素

Neurotoxin - Other CNS neurotoxin

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

吸收、分配和排泄

为了开发一种气相色谱-火焰离子化检测法（GC-FID）来测定冰片在小鼠组织中的浓度，并研究静脉注射和鼻腔给药后冰片的组织分布，收集了给予30.0 mg/kg冰片剂量后1、3、5、10、20、30、60、90、120分钟的小鼠大脑、心脏、肝脏、脾脏、肺和肾脏。用乙酸乙酯提取组织中的药物，并通过气相色谱检测冰片浓度，以十八烷为内标。校准曲线显示出良好的线性关系。提取回收率、日间和日内精密度及稳定性符合生物样本分析的要求。冰片主要分布在大多数组织中，心脏、大脑和肾脏中较多，肝脏、脾脏和肺中较少。建立的GC-FID方法适用于组织中冰片含量的测定。在小鼠静脉注射和鼻腔给药后，冰片主要分布在血液供应丰富的组织中。在鼻腔给药后，大脑组织显示出最高的靶向系数和靶向效果。

To develop a GC-FID method to determine borneol's concentration in mouse tissues, and to investigate the tissue distribution after intravenous and intranasal administrations of borneol, mouse brains, hearts, livers, spleens, lungs and kidneys were collected at 1, 3, 5, 10, 20, 30, 60, 90, 120 min after administration of borneol with the dose of 30.0 mg/kg. The drug in tissues was extracted with ethyl acetate, and borneol's concentration detected by GC, with octadecane as the internal standard. The calibration curve showed a good linear relationship. Extraction recoveries, inter-day and intra-day precisions and stability were in conformity with the analytical requirements of biological samples. Borneol was mainly distributed in most tissues, more in heart, brain and kidney, and less in liver, spleen and lung. The established GC-FID method is applicable for content determination of borneol in tissues. After intravenous and intranasal administrations in mice, borneol is mainly distributed in abundant blood-supply tissues. After intranasal administration, brain tissues showed the highest target coefficient and target effectiveness.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

为了理解静脉注射、鼻腔给药或口服给药后血液和大脑的药物动力学，并探讨鼻腔给药的优越性和可行性，开发了一种带有火焰离子化检测（FID）的简单气相色谱（GC）方法，用于定量测定冰片。在给小鼠静脉注射、鼻腔给药或口服给药30.0 mg/kg冰片后，分别于1、3、5、10、20、30、60、90和120分钟收集血液样本和大脑。样品前处理是通过使用辛烷内标溶液的液-液萃取来进行的。药代动力学参数是通过计算机软件计算得出的。血浆和大脑中冰片的校准曲线分别在0.11-84.24 ug/mL和0.16-63.18 ug/g范围内呈线性。方法学和萃取回收率均在85%-115%范围内。血浆和大脑样本的日内和日间变异性均小于或等于5.00%相对标准偏差（RSD）。鼻腔给药和口服给药的绝对生物利用度F分别为90.68%和42.99%。鼻腔给药和口服给药的相对大脑靶向系数Re分别为68.37%和38.40%。开发的GC-FID方法可用于测定和药代动力学研究。注射给药的冰片分布和代谢速度快，没有吸收过程。口服给药的冰片分布较慢，且绝对生物利用度最低。冰片的鼻腔给药能迅速吸收进入血液和大脑，使用方便，比注射更安全，这使得它值得作为治疗脑病的给药途径进一步开发。

... In order to understand the blood and brain pharmacokinetics after intravenous, intranasal, or oral administration and to investigate the superiority and feasibility of intranasal administration, a simple gas chromatographic (GC) method with flame ionization detection (FID) was developed for the quantification of borneol. Blood samples and brain were collected from mice at 1, 3, 5, 10, 20, 30, 60, 90, and 120 min after intravenous, intranasal, or oral administration of borneol at a dosage of 30.0 mg/kg. Sample preparations were carried out by liquid-liquid extraction with an internal standard solution of octadecane. The pharmacokinetic parameters were calculated /using computer software/. The calibration curves were linear in the range of 0.11-84.24 ug/mL and 0.16-63.18 ug/g for borneol in plasma and brain, respectively. The methodological and extraction recoveries were both in the range of 85%-115%. The intra-day and inter-day variabilities for plasma and brain samples were </= 5.00% relative standard deviation (RSD). The absolute bioavailabilities F of intranasal and oral administrations were 90.68% and 42.99%. The relative brain targeted coefficients Re of intranasal and oral administrations were 68.37% and 38.40%. The GC-FID method developed could be applied to determination and pharmacokinetic study. The borneol from injection was distributed and metabolized fast without absorption process. The borneol from oral administration was distributed more slowly and had the lowest absolute bioavailability. Nasal administration of borneol was quickly absorbed into the blood and brain, was easy to use and had a greater safety than infection, which makes it worthy of further development as an administration route for encephalopathy treatment.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

这项工作的目的是研究冰片的原位和活体鼻腔吸收。应用了一种新颖的单次通过原位鼻腔灌注技术来检查大鼠鼻腔吸收冰片的速率和程度。研究了灌注速率、pH值和药物浓度等实验条件。原位实验显示，冰片的鼻腔吸收不依赖于药物浓度，并且符合一级过程。吸收速率常数Ka随着灌注速度的增加而变化。在鼻咽腔的生理条件下，冰片在pH范围内和pH值条件下被很好地吸收。在大鼠中进行了冰片吸收的活体研究，并比较了鼻腔内给药（in）与静脉给药（iv）的药代动力学参数。冰片鼻腔内给药的生物利用度为90.82%，达到最大血药浓度的时间（Tmax）为10分钟。平均驻留时间（MRT）分别为262.55 +/- 67.35分钟和204.22 +/- 14.50分钟，分别对应鼻腔内给药和静脉给药。结果表明，冰片可以通过大鼠鼻腔内给药被迅速且彻底地吸收。

The aim of this work was to study the in situ and in vivo nasal absorption of borneol. A novel single pass in situ nasal perfusion technique was applied to examine the rate and extent of nasal absorption of borneol by rats. Experimental conditions, such as perfusion rate, pH and drug concentration, were investigated. The in situ experiments showed that the nasal absorption of borneol was not dependent on drug concentration, and fitted a first order process. The absorption rate constant, Ka, influenced with an increase in perfusion speed. The borneol was well absorbed in the conditions of the nasal cavity within the pH range and pH value of physiological conditions. In vivo studies of borneol absorption were carried out in rats and the pharmacokinetics parameters of intranasal (in) was compared with intravenous (iv) administration. The bioavailabilities of borneol was 90.82% for i.n. while Tmax values were 10 min. MRT (Mean Residence Time) were 262.55 +/- 67.35 min and 204.22 +/- 14.50 min for in and iv methods, respectively. The results demonstrate that borneol could be absorbed promptly and thoroughly by in administration in rats.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

先前的研究表明，冰片对中枢神经系统（CNS）具有双重作用，但机制尚不清楚。本研究的目的是阐明兴奋比率[兴奋性氨基酸（AAs）含量与抑制性氨基酸含量之比]与单次口服剂量后天然冰片含量的关系。小鼠通过口服摄入给予1.2 g/kg剂量的天然冰片（含98% D: -冰片）。在给药前和给药后0.083、0.167、0.25、0.333、0.5、0.75、1、1.5、2、2.5、3、4和5小时收集脑样本。通过GC-MS和HPLC-FLU分别测定小鼠脑中天然冰片的浓度和AA神经递质的含量。口服给药后，天然冰片迅速吸收进入大脑，给药后5分钟即可测定。给药后1小时达到最大脑浓度（86.52微克/克）。天然冰片可以影响小鼠脑中AA神经递质的含量：L: -门冬氨酸从给药后0.083至1小时显著增加，L: -谷氨酸在给药后0.333小时显著增加并在1.5至5小时降低，γ-氨基-N-丁酸从给药后0.167至5小时显著增加，而甘氨酸不受影响。兴奋比率是兴奋性AAs含量与抑制性AAs含量之比，反映了机体的兴奋或抑制状态。兴奋比率在给药后0.5小时暂时升高然后下降；在给药后1.5-5小时与给药前相比有显著差异。本研究表明，天然冰片可以影响AA神经递质的含量，兴奋比率的改变导致冰片对CNS的双重作用。

Previous studies have indicated that borneol has double side effects on the central nervous system (CNS), but the mechanism is unknown. The aim of this study was to clarify the relationship between excitation ratio [contents of excitatory amino acids (AAs) versus that of inhibitory] and the content of natural borneol after a single oral dose. Mice were administered a 1.2 g/kg dose of natural borneol (containing 98% D: -borneol) by oral ingestion. Brain samples were collected before administration and at 0.083, 0.167, 0.25, 0.333, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, and 5 hr after administration. The brain concentration of natural borneol and contents of AA neurotransmitters in mice brain were determined by GC-MS and HPLC-FLU, respectively. After per oral application, natural borneol was absorbed rapidly into the brain and could be determined 5 min after dosing. The maximal brain concentration (86.52 ug/g) was reached after 1 hr post-dosing. Natural borneol could affect the contents of AA neurotransmitters in mice brain: L: -aspartic acid increased significantly from 0.083 to 1 hr after administration, L: -glutamic acid increased significantly at 0.333 hr and decreased from 1.5 to 5 hr, gamma-amino-N-butyric acid increased significantly from 0.167 to 5 hr, whereas glycine was not affected. The excitation ratio is the contents of excitatory AAs versus that of inhibitory AAs, which reflects the excitatory or inhibitory state of the body. The excitation ratio elevated transitorily and then declined 0.5 hr post-dosing; there were significant differences between 1.5-5 hr post-dose compared with pre-dose. The present study indicated that natural borneol could affect the contents of AA neurotransmitters, and the change in excitatory ratio led to borneol's double side effects on the CNS.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

松节油、异冰片醇醋酸酯、柠檬烯、薄荷醇和α-蒎烯作为泡沫浴（Pinimenthol）成分的经皮吸收在动物身上进行了测量，使用放射性标记的成分。药代动力学测量显示，所有测试成分在经皮吸收开始后10分钟达到最大血药水平。没有成分被优先吸收。经皮吸收10分钟后所有成分的血药水平与涉及的皮肤面积大小直接相关。

The percutaneous absorptions of camphene, isoborneol-acetate, limonene, menthol and alpha-pinene as constituents of a foam bath (Pinimenthol) were measured on animals using radioactively labeled ingredients. Pharmacokinetic measurements showed maximum blood levels for all tested ingredients 10 min after the onset of percutaneous absorption. None of the ingredients was preferentially absorbed. Blood levels of all ingredients after 10 min of percutaneous absorption were a direct function of the size of the skin area involved.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  borneol 以93的产率得到樟脑
  参考文献：
  名称：

  J. Org. Chem. 2011, 76, 1390-1397

  摘要：

  DOI：
• 作为产物：
  描述：

  在 盐酸 作用下， 以 水 为溶剂， 以58%的产率得到
  参考文献：
  名称：

  TiCl4 催化酮与氨硼烷的硼氢化反应

  摘要：

  对多种路易斯酸与胺硼烷进行硼氢化水解（还原）的研究表明，室温下在乙醚中的催化（10 mol%）四氯化钛（TiCl 4 ）极大地加速了氨硼烷的反应。即使是在非催化条件下通常需要 24 小时或更长时间才能还原的酮，产品醇也可以在 30 分钟内以良好至极好的收率生产。几种潜在的反应性官能团是可以容忍的，并且取代的环烷酮被非对映选择性地还原为热力学产物。对反应进行了氘标记研究和11 B NMR 分析，以验证所提出的硼氢化机理。

  DOI：

  10.1021/acs.joc.2c01744
• 作为试剂：
  描述：

  对醛基苯甲酸 在 氯化亚砜 、 吡啶 、 borneol 作用下， 以 二氯甲烷 为溶剂， 反应 34.0h， 以60%的产率得到
  参考文献：
  名称：

  Borneol-triarylcorrole hybrids with chiral-optical response and anticancer behaviours

  摘要：

  DOI：

  10.1016/j.dyepig.2021.109699

文献信息

• Preparation of Mono-/Difluorinated Hydrocarbon Compounds
  申请人：Saint-Jalmes Laurent

  公开号：US20090234151A1

  公开（公告）日：2009-09-17

  Mono- or difluorinated hydrocarbon compounds are prepared from an alcohol or a carbonylated compound by reacting one of these with a fluorinating reagent, optionally in the presence of a base, the fluorinating agent comprising a pyridinium reactant having the following formula (F), wherein R 0 is an alkyl or cycloalkyl radical:

  从醇或羰基化合物中制备单氟或二氟烃化合物，通过将其中一种与氟化试剂反应制备，可选地在碱的存在下，氟化剂包括具有以下公式（F）的吡啶反应物，其中R0是烷基或环烷基基团。
• Method for the Direct Enantioselective Synthesis of Chiral Primary α-Amino Ketones by Catalytic α-Amination
  作者：Yixin Han、E. J. Corey

  DOI：10.1021/acs.orglett.8b03733

  日期：2019.1.4

  A useful catalytic enantioselective approach has been developed for the synthesis of chiral ketamine analogs using Rh(II)-catalyzed amination of triisopropylsilyl enol ethers to form α-amino ketones with O-(4-nitrophenyl)hydroxylamine as nitrogen donor in 81–91% ee.

  已开发出一种有用的催化对映选择性方法，用于合成手性氯胺酮类似物，该化合物使用Rh（II）催化的三异丙基甲硅烷基烯醇醚的胺化反应，以O-（4-硝基苯基）羟胺为氮供体，形成α-氨基酮，占81-91％ ee。
• AhR mediators
  申请人：Krutmann Jean

  公开号：US20090028804A1

  公开（公告）日：2009-01-29

  The invention relates to a method for finding and assessing agonists [and] antagonists of the aryl hydrocarbon receptor (Ah receptor; AhR), to the agonists and antagonists themselves and to uses thereof.

  这项发明涉及一种用于寻找和评估芳香族羟基化合物受体（Ah受体；AhR）的激动剂和拮抗剂的方法，以及这些激动剂和拮抗剂本身及其用途。
• Cosmetic compositions
  申请人：Symrise AG

  公开号：EP2745878A1

  公开（公告）日：2014-06-25

  Suggested is a cosmetic compositions comprising (a) a crosspolymer obtained from copolymerisation of at least two different polyols and at least one dicarboxylic acid and (b) at least one fragrance.

  建议的是一种化妆品组合物，包括 (a) 由至少两种不同的多元醇和至少一种二羧酸共聚得到的交联聚合物，以及 (b) 至少一种香料。
• Recherches sur la formation et la transformation de esters LII [1] Monoesters phosphoreux de divers types d'alcools
  作者：Emile Cherbuliez、F. Hunkeler、G. Weber、J. Rabinowitz

  DOI：10.1002/hlca.19640470629

  日期：——

  Menthol, unsaturated alcohols, and cyano alcohols are very easily esterified by phosphorous acid and yield the corresponding phosphorous monoesters.

  薄荷醇，不饱和醇和氰基醇很容易被亚磷酸酯化并生成相应的磷单酯。