(+)-冰片 | 507-70-0

• 物质功能分类: 食品添加剂 - 食品香料 - 天然等同香料
• 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
• 中文名称: (+)-冰片
• 中文别名: 内型-(1R)-1,7,7-三甲基二环[2.2.1]庚-2-醇；(+)-莰醇；内式-(1R)-1,7,7-三甲基双环[2.2.1]庚-2-醇；右旋莰醇
• 英文名称: d-borneol
• 英文别名: borneol；endo-borneol；dexborneol；(1R)-(+)-borneol；(+)-2-borneol；(1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol
• CAS: 507-70-0；464-43-7
• 化学式: C₁₀H₁₈O
• 分子量: 154.252
• InChiKey: DTGKSKDOIYIVQL-WEDXCCLWSA-N

物化性质

• 熔点：
  206-209 °C (lit.)
• 比旋光度：
  36 º (C=5 IN ETOH)
• 沸点：
  237.64°C (rough estimate)
• 密度：
  0.8704 (rough estimate)
• 闪点：
  150 °F
• 溶解度：
  DMF：25mg/mL； DMF:PBS(pH7.2)(1:2)：0.33mg/ml； DMSO：16mg/mL；乙醇：16mg/mL
• LogP：
  2.850
• 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 to off-white crystals
• 气味：
  Piney, camphor-like odor
• 味道：
  Burning taste somewhat reminiscent of mint
• 蒸汽压力：
  5.02X10-2 mm Hg at 25 °C
• 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：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试验中以Salmonella typhimurium TA1535、TA1537、TA1538、TA98和TA100菌株为对象进行了评估，冰片浓度高达5000微克/平板，在存在和不存在代谢激活的情况下。其他研究也证实了在S. typhimurium 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

• 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

为了研究冰片对具有不同亲水性和分子大小的化合物经角膜透过性的增强效果。选择了六种化合物作为模型药物，分别是罗丹明B、荧光素钠、异硫氰酸荧光素（FITC）葡聚糖，分子量分别为4、10、20和40 kDa。使用兔眼角膜的离体样本，通过Franz型扩散池进行透过性研究。根据角膜含水量和Draize眼刺激性试验来评估冰片的安全性。将0.2%的冰片应用于角膜，使罗丹明B、荧光素钠、4和10 kDa FITC-葡聚糖的表观渗透系数分别增加了1.82倍（p<0.05）、2.49倍（p<0.05）、4.18倍（p<0.05）和1.11倍（无统计学意义）。与对照组相比，10、20和40 kDa FITC-葡聚糖与冰片混合并未发现显著的透过性增强。0.2%冰片增强的渗透系数与模型药物的分子量呈线性相关（R(2)=0.9976）。使用0.05%、0.1%和0.2%的冰片后，角膜含水量值小于83%，Draize评分小于4。冰片可能改善亲水和疏水化合物的经角膜渗透性，而不会引起毒性反应，尤其是亲水性化合物。此外，0.2%的冰片可以增强分子量小于或等于4 kDa的亲水性化合物的渗透性。因此，冰片可以被认为是一种安全有效的眼部给药渗透增强剂。

To investigate the enhancing effect of borneol on transcorneal permeation of compounds with different hydrophilicities and molecular sizes. Six compounds, namely rhodamine B, sodium-fluorescein, fluorescein isothiocyanate (FITC) dextrans of 4, 10, 20 and 40 kDa were selected as model drugs. Permeation studies were performed using excised cornea of rabbits by a Franz-type diffusion apparatus. The safety of borneol was assessed on the basis of corneal hydration level and Draize eye test. The application of 0.2% borneol to the cornea increased the apparent permeability coefficient by 1.82-(p<0.05), 2.49-(p<0.05), 4.18-(p<0.05), and 1.11-fold (not significant) for rhodamine B, sodium-fluorescein, FITC-dextrans of 4 and 10 kDa, respectively. No significant permeability enhancement of FITC dextrans of 10, 20 and 40 kDa with borneol was found compared to control. The permeability coefficient enhanced by 0.2% borneol was linear correlated to the molecular weight of model drugs (R(2)=0.9976). With the 0.05%, 0.1% and 0.2% borneol application, the corneal hydration values were <83% and Draize scores were <4. Borneol may improve the transcorneal penetration of both hydrophilic and lipophilic compounds without causing toxic reactions, especially hydrophilic ones. Furthermore, 0.2% borneol can enhance the permeation of hydrophilic compounds with molecular weight </= 4 kDa. Hence, borneol can be considered as a safe and effective penetration enhancer for ocular drug administration.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

这项研究旨在通过MTT实验、流式细胞术和Western印迹法调查自然冰片/姜黄素（NB/Cur）对A375人类黑色素瘤细胞系生长和凋亡的协同效应。我们的结果显示，NB有效地与Cur协同作用，增强了对A375人类黑色素瘤细胞的抗增殖活性，通过诱导凋亡，表现为亚G1细胞群体增加、DNA断裂、PARP裂解和caspase活化。进一步的机制研究通过Western印迹法显示，细胞经NB/Cur处理后，磷酸化JNK表达水平上调和磷酸化ERK和Akt表达水平下调，促使A375细胞凋亡。此外，NB还增强了Cur触发细胞内ROS过度产生和DNA损伤的能力，同时上调了磷酸化ATM、磷酸化Brca1和磷酸化p53的表达水平。结果表明，NB和Cur联合应用在癌症治疗中具有潜在的应用价值。

This study was to investigate the synergistic effect of natural borneol/curcumin (NB/Cur) on growth and apoptosis in A375 human melanoma cell line by MTT assay, flow cytometry and Western blotting. Our results demonstrated that NB effectively synergized with Cur to enhance its antiproliferative activity on A375 human melanoma cells by induction of apoptosis, as evidenced by an increase in sub-G1 cell population, DNA fragmentation, PARP cleavage, and caspase activation. Further mechanistic studies by Western blotting showed that after treatment of the cells with NB/Cur, up-regulation of the expression level of phosphorylated JNK and down-regulation of the expression level of phosphorylated ERK and Akt contributed to A375 cells apoptosis. Moreover, NB also potentiated Cur to trigger intracellular ROS overproduction and the DNA damage with up-regulation of the expression level of phosphorylated ATM, phosphorylated Brca1 and phosphorylated p53. The results indicate the combinational application potential of NB and Cur in treatments of cancers.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

立即急救：确保已经进行了充分去污。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、气囊面罩装置或口袋面罩，按训练进行操作。根据需要执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者前倾或置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。/樟脑及其相关化合物/

Immediate First Aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Camphor and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

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、日间和日内精密度以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代谢动力学，并探讨鼻腔给药的优越性和可行性，开发了一种简单的气相色谱（GC）方法，配有火焰离子化检测（FID），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。药代动力学参数通过计算机软件计算。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。方法学回收率和萃取回收率均在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脑靶向系数Re分别为68.37%和38.40%。所开发的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迅速，无需吸收过程。口服给药的冰片分布较慢，具有最低的绝对生物利用度。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，这使得它作为治疗脑病的给药途径值得进一步开发。

... 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%，达到最大浓度的时间Tmax为10分钟。平均滞留时间MRT分别为262.55 +/- 67.35分钟和204.22 +/- 14.50分钟，分别对应于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，天然冰片迅速被吸收进入大脑，并在给药后5分钟可检测到。给药后1小时达到最大脑浓度（86.52微克/克）。天然冰片能够影响小鼠脑中AA神经递质的含量：L: -门冬氨酸在给药后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-氨基丁酸在给药后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小时与给药前有显著差异。本研究表明，天然冰片能够影响AA神经递质的含量，兴奋比率的改变导致了冰片对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)

安全信息

• 危险等级：
  4.1
• 危险品标志：
  F
• 安全说明：
  S16,S36/37
• 危险类别码：
  R22,R11
• WGK Germany：
  2
• 海关编码：
  2906199090
• 危险品运输编号：
  UN 1312
• 危险类别：
  4.1
• RTECS号：
  DT5095000
• 包装等级：
  III

制备方法与用途

冰片简介

冰片是从龙脑香科植物龙脑香（Dryobalanops aromatica Gaertn. f.）树脂加工品或其树干、树枝切碎后蒸馏冷却得到的结晶。也有称“龙脑冰片”、“梅片”。艾纳香（大艾，Blumea balsamifera DC.）叶的升华物经加工劈削而成，则称为“艾片”。现今多以松节油、樟脑等通过化学方法合成制成“机制冰片”。

龙脑香主要产于东南亚地区，我国台湾亦有引种。艾纳香则主产于广东、广西、云南、贵州等地。

化学成分

• 龙脑冰片 主要含右旋龙脑，并含有葎草烯、β-榄香烯、石竹烯等倍半萜类化合物，以及齐墩果酸、麦珠子酸、积雪草酸、龙脑香醇和古柯二醇等三萜化合物。
• 艾片 含有左旋龙脑。
• 机制冰片 由消旋混合的龙脑制成。

古籍摘要

1. 《新修本草》：用于治疗心腹邪气、风湿积聚、耳聋，明目，以及去除眼红和皮肤翳。
2. 《本草纲目》：用于治疗喉痹、脑痛、鼻息肉、牙齿疼痛、伤寒舌出等症状。可通诸窍，散郁火。
3. 《医林纂要》：冰片能够透骨热，治疗惊痫、痰迷、喉痹、牙痛、耳聋、鼻息、眼红浮翳等症，还能杀虫和痔疮，催生。然而其性质走而不守，易耗散最终归于阴寒。

药理作用

冰片中的主要成分龙脑和异龙脑具有耐缺氧的作用；有镇静效果；局部应用对感觉神经有轻微刺激，具备一定的止痛及温和的防腐作用；经肠系膜吸收迅速，可在5分钟内通过血脑屏障并在大脑中长期蓄积。较高浓度（0.5%）对葡萄球菌、链球菌、肺炎双球菌、大肠杆菌及部分致病性皮肤真菌有抑制作用；对中晚期妊娠小鼠有引产作用。

临床研究

• 将2～7mm大小的冰片置于0.6cm的胶布上贴于耳穴，用于治疗头痛。主穴选取神门、脑、皮质下（河南中医，1988，5：23）。
• 冰片溶于75%乙醇100ml中，用棉球蘸取后涂擦，可用于晚期肿瘤疼痛的治疗（中华护理杂志，1991，3：114）。
• 外用冰片霜治疗慢性肛门湿疹62例，结果显示治愈59例，总有效率98.4% (江苏中医，2001，5：30)。此外有单用冰片或配青黛、芒硝制成外用剂用于治疗多种外科感染性炎症。

冰片与麝香比较

• 药效比较：冰片与麝香同为开窍醒神之品，均可用于热病神昏、中风痰厥、气郁窍闭、中恶昏迷等闭证。然而麝香的开窍力强而冰片较逊色；麝香属温性开窍药，冰片则为凉性开窍剂；二者常相须为用。
• 外治作用：两者皆可消肿止痛和生肌敛疮，用于治疗疮疡肿毒。冰片侧重于清热泻火止痛，善治口齿、咽喉、耳目之疾；麝香则以活血散结、消肿止痛为主。

总之，冰片与麝香虽功效相似但性味不同，在具体应用上应根据患者病情适当选择和配伍。

反应信息

• 作为反应物：
  描述：

  (+)-冰片 在 2,4,5,6-四(9H-咔唑-9-基)异酞腈 、 [CoCl2(dmgH)2(pyridine)] 、 碘 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 乙腈 、 Petroleum ether 为溶剂， 反应 16.0h， 生成 (-)-bornylene
  参考文献：
  名称：

  合并卤素-原子转移 (XAT) 和钴催化以在消除烷基卤化物中超越 E2 选择性：走向逆热力学烯烃的温和途径

  摘要：

  我们在这里报告了一种在烷基卤化物上进行 E2 型消除的机械上不同的策略。该策略利用了 α-氨基烷基自由基介导的卤素原子转移 (XAT) 与去饱和钴催化的相互作用。该方法产量高，具有多种功能，并用于获取工业相关材料。与不对称底物产生区域异构混合物的热 E2 消除相比，这种方法能够通过微调钴催化剂的电子和空间性质，获得高烯烃位置选择性。这一史无前例的机械特性允许访问禁忌-thermodynamic烯烃，由E2淘汰难以捉摸。

  DOI：

  10.1021/jacs.1c06768
• 作为产物：
  描述：

  (+)-9-bromocamphor 在 4-二甲氨基吡啶 、 1-(dimethylamino)naphthaleimide 、 aluminum isopropoxide 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 异丙醇 为溶剂， 反应 96.25h， 生成 (+)-冰片
  参考文献：
  名称：

  Synthesis and absolute configuration of the antiparasitic furanosesquiterpenes (-)-furodysin and (-)-furodysinin. Camphor as a six-membered ring chiral pool template

  摘要：

  The syntheses of (-)-furodysin ((-)-2a) and (-)-furodysinin ((-)-3a) in four steps starting from (+)-9-bromocamphor (18) has been accomplished, thus establishing the absolute configuration of these and related metabolites. This was made possible by the unexpected exo selectivity in the aldol condensation of camphor-like enolates with aldehydes. This has been found to be a general phenomenon in the camphor system. Further, anionic fragmentation of the C1-C7 bond of camphor derivatives has allowed access to synthetic intermediates containing functionalized six-membered rings, thus opening up avenues from camphor to a new class of chiral pool elements not currently available from chiral pool substances.

  DOI：

  10.1021/jo00001a069
• 作为试剂：
  描述：

  1-碘丁烷 、 2-iodo-4-isopropyl-1-methoxybenzene 在 双(乙腈)氯化钯(II) 、 (+)-冰片 、 C₉H₁₃NO 、 caesium carbonate 、 2-羟基-5-三氟甲基吡啶 、 2-二苯基磷-2'-(N,N-二甲氨基)联苯 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 16.0h， 以52%的产率得到
  参考文献：
  名称：

  通过解决钯/降冰片烯催化中的“元约束”进入 1,2,3,4-四取代芳烃

  摘要：

  具有四个不同的连续取代基的芳烃，即 1,2,3,4-四取代的芳烃，通常在生物活性化合物中发现，但通过常规方法获得它们并非易事。通过解决钯/降冰片烯 (Pd/NBE) 协同催化中的“元约束”问题，即在芳基卤化物底物中难以容忍相当大的间位取代基，这里实现了一种模块化和区域选择性的方法来制备 1,2,3 ,4-四取代芳烃。一个关键是使用 C2-酰胺取代的 NBE，结合实验和计算研究揭示了它在促进 NBE 插入和邻位 CH 金属化步骤中的作用。范围很广：可以将各种亲电子试剂和亲核试剂分别引入邻位和邻位，并带有 1,4-二取代芳基卤化物，导致各种不对称的连续四取代芳烃。这种方法的应用已在几种生物活性化合物的流线型合成中得到证明。

  DOI：

  10.1021/jacs.9b12355

文献信息

• [EN] BIOACTIVE CONJUGATES FOR OLIGONUCLEOTIDE DELIVERY<br/>[FR] CONJUGUÉS BIOACTIFS POUR L'ADMINISTRATION D'OLIGONUCLÉOTIDES
  申请人：UNIV MASSACHUSETTS

  公开号：WO2017030973A1

  公开（公告）日：2017-02-23

  Provided herein are self-delivering oligonucleotides that are characterized by efficient RISC entry, minimum immune response and off-target effects, efficient cellular uptake without formulation, and efficient and specific tissue distribution.

  本文提供的自递送寡核苷酸具有高效的RISC进入、最小的免疫反应和非靶效应、无需配方的高效细胞摄取，以及高效和特异的组织分布。
• SBA-15-Functionalized 3-Oxo-ABNO as Recyclable Catalyst for Aerobic Oxidation of Alcohols under Metal-Free Conditions
  作者：Babak Karimi、Elham Farhangi、Hojatollah Vali、Saleh Vahdati

  DOI：10.1002/cssc.201402059

  日期：2014.9

  The nitroxyl radical 3‐oxo‐9‐azabicyclo [3.3.1]nonane‐N‐oxyl (3‐oxo‐ABNO) has been prepared using a simple protocol. This organocatalyst is found to be an efficient catalyst for the aerobic oxidation of a wide variety of alcohols under metal‐free conditions. In addition, the preparation and characterization of a supported version of 3‐oxo‐ABNO on ordered mesoporous silica SBA‐15 (SABNO) is described

  硝酰基自由基3-氧代-9-氮杂双环[3.3.1]壬烷-N-oxyl（3-oxo-ABNO）已使用简单的方案制备。已发现这种有机催化剂是在无金属条件下对多种醇进行好氧氧化的有效催化剂。此外，首次描述了在有序介孔二氧化硅SBA-15（SABNO）上支持的3-氧代ABNO的制备和表征。使用多种技术对催化剂进行了表征，包括同时热分析（STA），透射电子显微镜（TEM）和氮吸附分析。与（2,2,6,6-四甲基哌啶-1-基）氧基（TEMPO）相比，该催化剂在相同条件下几乎可以对相同范围的醇进行好氧氧化，其催化性能与其均相类似物相当，并且催化活性要好得多。反应条件。
• RENIN INHIBITORS
  申请人：Jones Benjamin

  公开号：US20100210635A1

  公开（公告）日：2010-08-19

  Compounds, pharmaceutical compositions, kits and methods are provided for use with Renin that comprise a compound selected from the group consisting of: wherein the variables are as defined herein.

  提供了用于与Renin一起使用的化合物、药物组合物、试剂盒和方法，其中包括从以下组中选择的化合物：其中变量如本文所定义。
• Novel pyridine derivative and pyrimidine derivative
  申请人：Matsushima Tomohiro

  公开号：US20050277652A1

  公开（公告）日：2005-12-15

  A compound represented by the following formula, a salt thereof or a hydrate of the foregoing has an excellent hepatocyte growth factor receptor (HGFR) inhibitory activity, and exhibits anti-tumor activity, angiogenesis inhibitory activity and cancer metastasis inhibitory activity. [R 1 represents C 1-6 alkyl or the like; R 2 and R 3 represent hydrogen; R 4 , R 5 , R 6 , and R 7 may be the same or different and each represents hydrogen, halogen, C 1-6 alkyl or the like; R 8 represents hydrogen or the like; R 9 represents C 1-6 alkyl or the like; V 1 represents oxygen or the like; V 2 represents oxygen or sulfur; W represents —NH— or the like; X represents —CH═, nitrogen or the like; and Y represents oxygen or the like.]

  以下化合物的分子式，其盐或前述水合物具有出色的肝细胞生长因子受体（HGFR）抑制活性，并表现出抗肿瘤活性、抑制血管生成活性和抑制癌转移活性。 [R 1 代表C 1-6 烷基或类似物；R 2 和R 3 代表氢；R 4 ，R 5 ，R 6 和R 7 可以相同也可以不同，每个代表氢、卤素、C 1-6 烷基或类似物；R 8 代表氢或类似物；R 9 代表C 1-6 烷基或类似物；V 1 代表氧或类似物；V 2 代表氧或硫；W代表—NH—或类似物；X代表—CH═、氮或类似物；Y代表氧或类似物。]
• [EN] TARGETED DRUG DELIVERY THROUGH AFFINITY BASED LINKERS<br/>[FR] ADMINISTRATION CIBLÉE D'UN MÉDICAMENT FAISANT APPEL À DES COUPLEURS FONDÉS SUR L'AFFINITÉ
  申请人：INVICTUS ONCOLOGY PVT LTD

  公开号：WO2015148126A1

  公开（公告）日：2015-10-01

  The current invention discloses targeted drug delivery conjugates comprising a targeting moiety linked to a drug via a molecule having an affinity for the targeting moiety. Typically, the conjugate comprises a targeting ligand and a molecule of interest, e.g., a therapeutic agent. The targeting ligand and the molecule of interest are linked to each other via an affinity ligand. The affinity ligand is further covalently or non-covalently linked to a drug or therapeutic agent. The drug can be modified to make it more soluble and so that it cleaves from the linking molecule at the target site.

  当前的发明揭示了包括通过具有与靶向基团亲和力的分子连接到药物的靶向药物传递共轭物。通常，该共轭物包括一个靶向配体和一个感兴趣的分子，例如，一个治疗剂。靶向配体和感兴趣的分子通过一个亲和配体相互连接。该亲和配体进一步以共价或非共价方式连接到药物或治疗剂。药物可以被修改以使其更溶解，并使其在靶点处从连接分子中解离。

表征谱图