维基百科

冰片

化合物

冰片（分子式：C10H18O），又名片脑、桔片、龙脑香、梅花冰片、羯布罗香、梅花脑、冰片脑、梅冰、龍腦、瑞脑、腦子、天然冰片、老梅片、梅片、莰醇等，是由2个异戊二烯结构单元组成的环状化合物，属于单萜衍生物[1]。根据旋光性分为左旋龙脑（(-)-龙脑）和右旋龙脑（(+)-龙脑）[2]。右旋龙脑主要来源于龙脑樟和阴香树[3]，而左旋龙脑主要来源于菊科植物[4]。《中国药典》中右旋者来自樟枝叶，左旋者来自艾纳香。[5]

冰片
冰片
IUPAC名
endo-1,7,7-Trimethyl- bicyclo[2.2.1]heptan-2-ol
识别
CAS号 507-70-0  checkY
464-43-7（(+)）  checkY
464-45-9（(-)）  checkY
PubChem 6552009
ChemSpider 5026296
SMILES
 
  • CC1(C2(C)C)C(O)CC2CC1
InChI
 
  • 1/C10H18O/c1-9(2)7-4-5-10(9,3)8(11)6-7/h7-8,11H,4-6H2,1-3H3/t7-,8+,10+/m1/s1
InChIKey DTGKSKDOIYIVQL-WEDXCCLWBQ
ChEBI 15393
KEGG C01411
IUPHAR配体 6413
性质
化学式 C10H18O
密度 1.011 g/cm3 @ 20oC
熔点 208°C
沸点 易升华
危险性
欧盟危险性符号
有害有害 Xn
易燃易燃 F
警示术语 R：R33-R36/37/38
安全术语 S：S26-S37
MSDS 英文MSDS
若非注明，所有数据均出自标准状态（25 ℃，100 kPa）下。

合成

生物合成

冰片的合成前体由细胞质中的甲羟戊酸途径和质体中的4-磷酸-2-甲基赤藓糖途径产生的异戊烯基焦磷酸和二甲基烯丙基焦磷酸合成[6]。在香叶基焦磷酸合酶的催化作用下，这些合成物缩合生成香叶基焦磷酸[7]，随后在二磷酸龙脑合酶的作用下环化成二磷酸龙脑，最终在碱性磷酸酶的作用下脱去磷酸基团生成龙脑[2]。

冰片的手性具体取决于二磷酸龙脑合酶偏好的手性。目前已知一个二磷酸左旋龙脑合成酶的序列和多个二磷酸右旋龙脑合成酶的序列。[8]

此外，龙脑在龙脑脱氢酶的催化作用下被氧化成樟脑[9]。

人工合成

冰片极易被氧化成酮而生成樟脑，人工合成方法是通过Meerwein–Ponndorf–Verley还原反应将樟脑还原成冰片。中国所谓“合成冰片”是以消旋樟脑为起点，得到的冰片和异冰片的消旋混合物，实际操作中还可能有未反应的樟脑杂质[5]。“半合成冰片”则是以单独一个手性的樟脑开始：(+)-樟脑还原可得(+)-冰片和(-)-异冰片[10]。

加入硼氢化钠可以加快反应速率，使反应成为不可逆反应，但是产物也由于动力学控制变成异冰片。

 
樟脑被还原成异冰片

利用

冰片被认为具有抗菌、保护心脑血管、镇痛消炎、防止血栓、促进药物透过血脑屏障等多种作用[11]。常应用于临床治疗，作为止痛剂、镇痛剂和麻醉剂[12]。

中国有依达拉奉/右莰醇复方药，其中右莰醇就是右旋冰片。有注射液、舌下含片版本，批准用来改善急性缺血性脑卒中后遗症，号称比单独依达拉奉更有效。[13][14]

毒性

冰片具有剂量毒性，大量使用会引起毒性反应。[15]

參考資料

  1. ^ Wang, Hong; Ma, Dongming; Yang, Jinfen; Deng, Ke; Li, Meng; Ji, Xiaoyu; Zhong, Liting; Zhao, Haiying. An Integrative Volatile Terpenoid Profiling and Transcriptomics Analysis for Gene Mining and Functional Characterization of AvBPPS and AvPS Involved in the Monoterpenoid Biosynthesis in Amomum villosum. Frontiers in Plant Science. 2018-06-20, 9. doi:10.3389/fpls.2018.00846. 
  2. ^ 2.0 2.1 Chen, Changjie; Miao, Yuhuan; Luo, Dandan; Wang, Zixin; Guo, Lujuan; Zhao, Tingting; Liu, Dahui. Cloning and Functional Verification of the Borneol Dehydrogenase Encoding Gene AArBDH1 in Artemisia argyi. Chinese Bulletin of Botany. 2023-07-01, 58 (4): 560. doi:10.11983/CBB22123. 
  3. ^ Xingxing, Liu; Xi, Zhang; Xiali, Guo; Shangji, Gong; Xiangmei, Jiang; Yuxin, Fu; Liping, Luo. Multivariate Analyses of Volatile Chemical Composition in Leaves of Different Cinnamomum camphora Chemotypes. Chinese Bulletin of Botany. 2014, 49 (2): 161. doi:10.3724/SP.J.1259.2014.00161. 
  4. ^ Ho, Tsung-Jung; Hung, Chien-Che; Shih, Tzenge-Lien; Yiin, Lih-Ming; Chen, Hao-Ping. Investigation of borneols sold in Taiwan by chiral gas chromatography. Journal of Food and Drug Analysis. 2018-01, 26 (1): 348–352. doi:10.1016/j.jfda.2016.10.012. 
  5. ^ 5.0 5.1 中国药典第一部 2020.  右旋 左旋 合成
  6. ^ 徐应文; 吕季娟; 吴卫; 郑有良. 植物单萜合酶研究进展. 生态学报. 2009, 29 (6): 3188–3197 [2024-03-10]. ISSN 1000-0933. CNKI STXB200906052. （原始内容存档于2024-03-10）. 
  7. ^ 赵圆圆; 孙叶雯; 郑诗敏; 李萌; 马东明; 杨锦芬. 阳春砂龙脑基二磷酸合酶关键氨基酸位点筛选及突变体的构建. 中草药. 2022, 53 (2): 529–537 [2024-03-10]. doi:10.7501/j.issn.0253-2670.2022.02.023. CNKI ZCYO202202022. （原始内容存档于2024-03-10）. 
  8. ^ Ma, Rui; Su, Ping; Ma, Qing; Guo, Juan; Chen, Suiqing; Jin, Baolong; Zhang, Haiyan; Tang, Jinfu; Zhou, Tao; Xiao, Chenghong; Cui, Guanghong; Huang, Luqi. Identification of (-)-bornyl diphosphate synthase from Blumea balsamifera and its application for (-)-borneol biosynthesis in Saccharomyces cerevisiae. Synthetic and Systems Biotechnology. 2022-03, 7 (1): 490–497. PMC 8671873  . PMID 34977393. doi:10.1016/j.synbio.2021.12.004. 
  9. ^ Hurd, Matthew C.; Kwon, Moonhyuk; Ro, Dae-Kyun. Functional identification of a Lippia dulcis bornyl diphosphate synthase that contains a duplicated, inhibitory arginine-rich motif. Biochemical and Biophysical Research Communications. 2017-08, 490 (3): 963–968. doi:10.1016/j.bbrc.2017.06.147. 
  10. ^ Yang, Ming‐Yeh; Khine, Aye Aye; Liu, Jen‐Wei; Cheng, Hui‐Chen; Hu, Anren; Chen, Hao‐Ping; Shih, Tzenge‐Lien. Resolution of isoborneol and its isomers by GC/MS to identify “synthetic” and “semi‐synthetic” borneol products. Chirality. November 2018, 30 (11): 1233–1239. doi:10.1002/chir.23017. 
  11. ^ Ma, Rui; Su, Ping; Guo, Juan; Jin, Baolong; Ma, Qing; Zhang, Haiyan; Chen, Lingli; Mao, Liuying; Tian, Mei; Lai, Changjiangsheng; Tang, Jinfu; Cui, Guanghong; Huang, Luqi. Bornyl Diphosphate Synthase From Cinnamomum burmanni and Its Application for (+)-Borneol Biosynthesis in Yeast. Frontiers in Bioengineering and Biotechnology. 2021-02-11, 9. doi:10.3389/fbioe.2021.631863. 
  12. ^ Khine, Aye Aye; Lu, Pei-Chieh; Ko, Tzu-Ping; Huang, Kai-Fa; Chen, Hao-Ping. Cloning, expression, identification and characterization of borneol dehydrogenase isozymes in Pseudomonas sp. TCU-HL1. Protein Expression and Purification. 2020-11, 175: 105715. doi:10.1016/j.pep.2020.105715. 
  13. ^ 先声药业. 先必新 依达拉奉右莰醇舌下片说明书 (PDF). 
  14. ^ Xu, Jie; Wang, Anxin; Meng, Xia; Yalkun, Gulbahram; Xu, Anding; Gao, Zhiqiang; Chen, Huisheng; Ji, Yong; Xu, Jun; Geng, Deqin; Zhu, Runxiu; Liu, Bo; Dong, Aiqin; Mu, Hua; Lu, Zhihong; Li, Shuya; Zheng, Huaguang; Chen, Xia; Wang, Yilong; Zhao, Xingquan; Wang, Yongjun; Wang, Yongjun; Xu, Anding; Zhao, Xingquan; Chen, Xia; Wang, Yongjun; Meng, Xia; Wang, Yilong; Xu, Jie; Wang, Anxin; Zheng, Huaguang; Gao, Zhiqiang; Duan, Lei; Zhang, Jinghua; Li, Shuya; Lou, Donghua; Gao, Zhiqiang; Chen, Huisheng; Ji, Yong; Xu, Jun; Geng, Deqin; Zhu, Runxiu; Liu, Bo; Dong, Aiqin; Liang, Qingcheng; Yang, Hong; Guo, Cunju; Li, Xin; He, Mingli; Tian, Xiangyang; Cui, Yong; Zhou, Junshan; Wang, Ning; Wang, Lei; Zhang, Xinjiang; Gao, Xiaoping; Lu, Liping; Li, Tong; Cheng, Yan; Liu, Kaixiang; Xi, Xiaokun; Wang, Baojun; Sun, Lin; Zhao, Shigang; Chu, Xiaofan; Lian, Yajun; Yan, Fuling; Wang, Xiaoshan; Wang, Dong; Shao, Bei; Jiao, Jinsong; Wu, Heng; Li, Guanglai; Guo, Libin; Wang, Yongjun; Pan, Suyue; Xu, Anding; Li, Heng; Zhuang, Jianhua; Li, Xin; Wu, Jun; Wang, Anxin; Lou, Donghua; Zuo, Yingting; Zhang, Yijun; Zhang, Xiaoli; Feng, Xiaofei; Meng, Xia; Wang, David; Dong, Kehui; Liu, Yanfang; Li, Hao; Chen, Dawei; Lv, Qiushi. Edaravone Dexborneol Versus Edaravone Alone for the Treatment of Acute Ischemic Stroke: A Phase III, Randomized, Double-Blind, Comparative Trial. Stroke. March 2021, 52 (3): 772–780. PMID 33588596. doi:10.1161/STROKEAHA.120.031197. 
  15. ^ Material Safety Data Sheet, Fisher Scientific. [2022-10-01]. （原始内容存档于2022-10-04）. 

外部連結

检索自“https://zh.wikipedia.org/w/index.php?title=冰片&oldid=85427700”