(-)-borneol | 881024-40-4

• 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: isoborneol；(2R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol
• CAS: 881024-40-4
• 化学式: C₁₀H₁₈O
• 分子量: 154.252
• InChiKey: DTGKSKDOIYIVQL-CCNFQMFXSA-N

物化性质

• 沸点：
  212.0±0.0 °C(Predicted)
• 密度：
  0.992±0.06 g/cm3(Predicted)
• 物理描述：
  Borneol appears as a white colored lump-solid with a sharp camphor-like odor. Burns readily. Slightly denser than water and insoluble in water. Used to make perfumes.
• 颜色/状态：
  White solid
• 气味：
  Camphor odor
• 熔点：
  209.33333333329998 °C
• 溶解度：
  In water, 1.19X10+3 mg/L at 25 °C (est)
• 蒸汽压力：
  3.53X10-2 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Stable under recommended storage conditions.
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 气味阈值：
  Detection: 2.5 to 16 ppb

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：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：在一项人类最大量测试中，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，异冰片对人体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也没有表现出显著的细胞毒性。查阅了化学物质l-冰片和异冰片醋酸酯的遗传毒性、重复剂量毒性、发育和生殖毒性评估。在针对大鼠进行的异冰片醋酸酯13周亚慢性毒性研究中，基于增加的尿液细胞排泄，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，确定异冰片醋酸酯的无观察到有害效应水平（NOAEL）为300 mg/kg/天。l-冰片在Ames试验中不是致突变剂。异冰片在Bluescreen检测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，对遗传毒性和细胞毒性都是阴性的。

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

毒理性

• 相互作用

多巴胺（DA）引起的氧化应激可能在帕金森病（PD）的发病机制中发挥重要作用。(+/-)异冰片是一种单萜醇，存在于许多药用植物的精油中，是一种已知的抗氧化剂。在本研究中，我们探讨了异冰片对6-羟基多巴胺（6-OHDA）诱导的人神经母细胞瘤SH-SY5Y细胞死亡的神经保护作用。用异冰片预处理SH-SY5Y细胞显著减少了6-OHDA诱导的活性氧种（ROS）的产生和6-OHDA诱导的细胞内钙的增加。此外，异冰片处理逆转了6-OHDA诱导的凋亡。异冰片保护细胞免受6-OHDA诱导的胱天蛋白酶-3活性增加和细胞色素C从线粒体转移到细胞质的影响。异冰片阻止了6-OHDA降低Bax/Bcl-2比例的作用。我们还观察到，异冰片降低了c-Jun N末端激酶的激活，并诱导了6-OHDA所抑制的蛋白激酶C（PKC）的激活。我们的结果表明，异冰片的保护功能取决于其抗氧化潜力，强烈提示异冰片可能是治疗与氧化应激相关的神经退行性疾病的有效治疗方法。

Oxidative stress caused by dopamine (DA) may play an important role in the pathogenesis of Parkinson's disease (PD). (+/-) Isoborneol is a monoterpenoid alcohol present in the essential oils of numerous medicinal plants and is a known antioxidant. In this study, we investigated the neuroprotective effect of isoborneol against 6-hydroxydopamine (6-OHDA)-induced cell death in human neuroblastoma SH-SY5Y cells. Pretreatment of SH-SY5Y cells with isoborneol significantly reduced 6-OHDA-induced generation of reactive oxygen species (ROS) and 6-OHDA-induced increases in intracellular calcium. Furthermore, apoptosis induced by 6-OHDA was reversed by isoborneol treatment. Isoborneol protected against 6-OHDA-induced increases in caspase-3 activity and cytochrome C translocation into the cytosol from mitochondria. Isoborneol prevented 6-OHDA from decreasing the Bax/Bcl-2 ratio. We also observed that isoborneol decreased the activation of c-Jun N-terminal kinase and induced activation of protein kinase C (PKC) which had been suppressed by 6-OHDA. Our results indicate that the protective function of isoborneol is dependent upon its antioxidant potential and strongly suggest that isoborneol may be an effective treatment for neurodegenerative diseases associated with oxidative stress.

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使用放射性标记成分进行了测量。药代动力学测量显示，所有测试成分在开始经皮吸收后10分钟达到最大血药水平。没有任何成分表现出优先吸收。所有成分在经皮吸收10分钟后的血药水平与涉及皮肤面积的大小成正比。

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 在 (1R,2R)-1,2-di(naphthalen-1-yl)ethane-1,2-diamine 、 叔丁基过氧化氢 、 potassium carbonate 作用下， 以 水 为溶剂， 反应 16.0h， 以161.4 mg的产率得到左旋樟脑
  参考文献：
  名称：

  使用 1,2-二(1-萘基)-1,2-乙二胺 (NEDA) 有机催化氧化仲醇

  摘要：

  二胺，1,2-二(1-萘基)-1,2-乙二胺 (NEDA)，通过使用 TBHP 作为氧化剂有效地催化醇的氧化。值得注意的是，仲苄醇以几乎定量的产率被氧化，并且该催化剂甚至对受阻的脂环族仲醇也表现出高活性。使用对映体纯 (R,R)-NEDA，可以实现氧化动力学拆分，并且取决于醇度，可以实现高达 99% 的 ee。

  DOI：

  10.1002/ejoc.201402991
• 作为产物：
  描述：

  L-乙酸冰片酯 在 三乙基氢硼化钾 、 1,1'-di-methyl-3,3'-ethylenebis(imidazol-2-ylidene)-2,2-manganese tricarbonylbromide 作用下， 以 四氢呋喃 为溶剂， 60.0 ℃ 、5.0 MPa 条件下， 以94 %的产率得到(-)-borneol
  参考文献：
  名称：

  双（N-杂环卡宾）锰（I）配合物：高效且简单的加氢催化剂

  摘要：

  研究了带有简单非双功能双 (NHC) 配体的锰 (I) 配合物作为加氢催化剂。应用这些配合物与 KHBEt 3作为添加剂，各种羧酸酯以及酮、腈、N-杂芳烃和烯烃被成功氢化。通过控制实验和 DFT 计算进行的机理研究表明了内球机理，并揭示了 BEt 3作为助催化剂的作用。

  DOI：

  10.1002/anie.202307987
• 作为试剂：
  描述：

  吗啉-4-基苯甲酸酯 、 (4-Bromo-3-methylphenyl)-(4-fluorophenyl)methanone 在 norbornene 、 (-)-borneol 、 1,4-双(二环己基膦)丁烷 、 palladium diacetate 、 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 14.0h， 以47%的产率得到
  参考文献：
  名称：

  钯/降冰片烯协同催化芳基硼氧烷的氧化还原中性邻位官能化

  摘要：

  钯/降冰片烯（Pd / NBE）协同催化，也称为Catellani反应，已成为位点选择性芳烃官能化的一种越来越有用的方法。但是，由于其固有的机理途径，仍然存在某些限制。在这里，我们报告通过Pd / NBE催化的芳基硼氧烷的氧化还原中性邻位官能化。亲电子试剂，例如羧酸酐或O-苯甲酰基羟胺，在环硼氧烷邻位偶联，质子作为第二种亲电子试剂引入ipso位置。该反应不需要额外的氧化剂或还原剂，并且避免了化学计量的碱或酸，从而可以耐受各种官能团。特别地，证明了芳基碘和环硼氧烷部分之间的正交化学选择性，其可用于控制反应序列。最后，氘标记研究支持ipso质子化途径。这种独特的机械特性可能会激发新型Pd / NBE催化的转化的发展。

  DOI：

  10.1016/j.chempr.2019.02.005

文献信息

• Process for producing optically active compound
  申请人：Tokunaga Makoto

  公开号：US20060173210A1

  公开（公告）日：2006-08-03

  A process for producing an optically active compound based on the hydrolysis of an alkenyl ester compound or the cleavage of an alkenyl ether compound. The process uses neither an acidic compound nor a basic compound, and rectants can be reacted in a high concentration. It does not necessitate a buffer, nutrient, etc. unlike enzymatic reactions or reactions using a microorganism. It is a simple process which attains a satisfactory production efficiency. The process, which is for producing an optically active carboxylic acid or optically active alcohol represented by the general formula (VI): (wherein R 1 , R 2 , and R 3 are different groups; and A represents methylene, carbonyl, or a single bound), is characterized by causing water to act on an alkenyl ester or alkenyl ether represented by the general formula (I): (wherein R 4 , R 5 , and R 6 each represents hydrogen, alkyl, etc.) in the presence of a specific transition metal complex having an optically active ligand.

  一种基于烯基酯化合物的水解或烯基醚化合物的裂解制备光学活性化合物的方法。该过程既不使用酸性化合物也不使用碱性化合物，反应物可以在高浓度下反应。与酶反应或使用微生物的反应不同，它不需要缓冲剂、营养物等。这是一个简单的过程，可以实现令人满意的生产效率。该过程用于制备由通式（VI）表示的光学活性羧酸或光学活性醇，其特征在于在具有光学活性配体的特定过渡金属配合物存在下，使水作用于通式（I）表示的烯基酯或烯基醚（其中R4、R5和R6分别表示氢、烷基等）。
• Dehydrogenative Silylation of Alcohols Under Pd‐Nanoparticle Catalysis
  作者：Suman Pramanik、Anthony Fernandes、Virginie Liautard、Mathieu Pucheault、Frederic Robert、Yannick Landais

  DOI：10.1002/chem.201803989

  日期：2019.1.14

  hydrosilanes and alcohols was shown to provide silyl ethers in good and reproducible yields. The synthetic methodology is effective for a wide range of simple and bulky silanes and secondary alcohols, while keeping various other functional groups intact. The procedure also exhibits high selectivity for the silylation of primary versus secondary alcohols in 1,2‐diols, and allows the successive silylation of alkynols

  研究表明，各种氢化硅烷与醇之间的钯纳米粒子催化的脱氢偶联作用可提供良好且可重现的甲硅烷基醚。合成方法可有效用于各种简单而庞大的硅烷和仲醇，同时保持各种其他官能团的完整性。该方法对1,2-二醇中伯醇和仲醇的甲硅烷基化反应也显示出很高的选择性，并且可以使炔醇进行连续的甲硅烷基化反应和三键氢化，从而以高收率得到Z-链烯醇。
• [EN] PRODRUG OF AMINO ACID DERIVATIVE<br/>[FR] PROMÉDICAMENT DE DÉRIVÉ D'ACIDE AMINÉ
  申请人：TAISHO PHARMA CO LTD

  公开号：WO2017183734A1

  公开（公告）日：2017-10-26

  Provided is an amino acid derivative prodrug represented by general formula (I-A) that is a prodrug form of an amino acid derivative which is a group 2 metabotropic glutamate receptor antagonist, or a pharmaceutically acceptable salt thereof. More specifically, provided is an amino acid derivative prodrug represented by general formula (I-A) that is a preventive or therapeutic drug for mood disorders (including depression and bipolar disorder), anxiety disorder, cognitive disorders, developmental disorders, Alzheimer's disease, Parkinson's disease, movement disorders associated with muscular rigidity, sleep disorders, Huntington's chorea, eating disorders, drug dependence, epilepsy, brain infarction, cerebral ischemia, cerebral insufficiency, cerebral edema, spinal cord disorders, head trauma, inflammation and immune- related diseases, and so on.

  提供的是一种氨基酸衍生物前药，代表为一般式(I-A)，它是一种群2代谷氨酸代谢型谷氨酸受体拮抗剂的前药形式，或其药学上可接受的盐。更具体地，提供的是一种氨基酸衍生物前药，代表为一般式(I-A)，用于预防或治疗情绪障碍（包括抑郁症和躁郁症）、焦虑症、认知障碍、发育障碍、阿尔茨海默病、帕金森病、伴有肌肉僵硬的运动障碍、睡眠障碍、亨廷顿舞蹈症、进食障碍、药物依赖、癫痫、脑梗死、脑缺血、脑供血不足、脑水肿、脊髓疾病、头部创伤、炎症和免疫相关疾病等。
• Antileishmanial Lead Structures from Nature: Analysis of Structure-Activity Relationships of a Compound Library Derived from Caffeic Acid Bornyl Ester
  作者：Jan Glaser、Martina Schultheis、Sudipta Hazra、Banasri Hazra、Heidrun Moll、Uta Schurigt、Ulrike Holzgrabe

  DOI：10.3390/molecules19021394

  日期：——

  Bioassay-guided fractionation of a chloroform extract of Valeriana wallichii (V. wallichii) rhizomes lead to the isolation and identification of caffeic acid bornyl ester (1) as the active component against Leishmania major (L. major) promastigotes (IC50 = 48.8 µM). To investigate the structure-activity relationship (SAR), a library of compounds based on 1 was synthesized and tested in vitro against L. major and L. donovani promastigotes, and L. major amastigotes. Cytotoxicity was determined using a murine J774.1 cell line and bone marrow derived macrophages (BMDM). Some compounds showed antileishmanial activity in the concentration range of pentamidine and miltefosine which are the standard drugs in use. In the L. major amastigote assay compounds 15, 19 and 20 showed good activity with relatively low cytotoxicity against BMDM, resulting in acceptable selectivity indices. Molecules with adjacent phenolic hydroxyl groups exhibited elevated cytotoxicity against murine cell lines J774.1 and BMDM. The Michael system seems not to be essential for antileishmanial activity. Based on the results compound 27 can be regarded as new lead structure for further structure optimization.

  在对 Valeriana wallichii (V. wallichii) 根茎的氯仿提取物进行生物测定引导的分馏时，成功分离并鉴定出咖啡酸伯基酯 (1)，作为对 Leishmania major (L. major) 萌发体的活性成分（IC50 = 48.8 µM）。为了研究结构-活性关系 (SAR)，基于化合物 1 合成了一系列化合物，并在体外测试了它们对 L. major 和 L. donovani 萌发体和 L. major 非芽孢体的活性。通过使用鼠类 J774.1 细胞系和骨髓来源的巨噬细胞 (BMDM) 测定了细胞毒性。一些化合物在与标准药物五氟苯和米氟喹范围内的浓度下表现出抗利什曼病活性。在 L. major 非芽孢体实验中，化合物 15、19 和 20 显示出良好的活性，同时对 BMDM 的细胞毒性相对较低，产生了可接受的选择性指数。相邻的酚羟基化合物对鼠类细胞系 J774.1 和 BMDM 显示出较高的细胞毒性。Michael 体系似乎对于抗利什曼病活性并不是必需的。根据结果，化合物 27 可被视为进一步结构优化的新型先导结构。
• [EN] BORONIC ACID DERIVATIVES AND SYNTHESIS THEREOF<br/>[FR] DÉRIVÉS D'ACIDE BORONIQUE ET SYNTHESE DE CES DERNIERS
  申请人：QPEX BIOPHARMA INC

  公开号：WO2019075084A1

  公开（公告）日：2019-04-18

  Disclosed herein are antimicrobial compounds compositions, pharmaceutical compositions, the method of use and preparation thereof. Some embodiments relate to boronic acid derivatives and their use as therapeutic agents, for example, β-lactamase inhibitors (BLIs).

  本文揭示了抗微生物化合物组合物、药物组合物、使用方法及其制备。一些实施例涉及硼酸衍生物及其作为治疗剂的用途，例如β-内酰胺酶抑制剂（BLIs）。

表征谱图