冰片

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 ; 464-43-7（(+)） ; 464-45-9（(-)）
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 Xn 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。

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、龙脑、瑞脑、脑子、天然冰片、老梅片、梅片等，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和右旋龙脑^[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]。

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^[5]。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^[6]，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。^[7]

此外，龙脑在龙脑脱氢酶的催化作用下被氧化成樟脑^[8]。

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。“半合成冰片”则是以单独一个手性樟脑开始：(+)-樟脑还原可得(+)-冰片和(-)-异冰片。^[9]

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^[10]。常应用于临床治疗，作为止痛剂、镇痛剂和麻醉剂^[11]。

毒性

冰片具有剂量毒性，大量使用会引起毒性反应。^[12]

参考资料

^ 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.
^ ^2.0 ^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.
^ 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.
^ 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.
^ 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）.
^ 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）.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ Material Safety Data Sheet, Fisher Scientific. [2022-10-01]. （原始内容存档于2022-10-04）.

外部链接

冰片中药材图像数据库 (香港浸会大学中医药学院) （中文）（英文）
冰片 Bing Pian（页面存档备份，存于互联网档案馆）中药标本数据库（香港浸会大学中医药学院）（繁体中文）（英文）
梅花冰片 Mei Hua Bing Pian（页面存档备份，存于互联网档案馆）中药标本数据库（香港浸会大学中医药学院）（繁体中文）（英文）

[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.

[CBB22123-2] 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] 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）.

[6] 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）.

[7] 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.

[8] 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.

[9] 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.

[10] 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.

[11] 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.

[12] Material Safety Data Sheet, Fisher Scientific. [2022-10-01]. （原始内容存档于2022-10-04）.

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