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1、Chinese Medicinal ChemistrySchool of Chinese PharmacyBeijing University of Chinese MedicineZengping Gao Sep.2009 Chapter 9 Terpenoids and Volatile Oils萜和挥发油萜和挥发油 *Terpenoids *Volatile Oils9.1 Terpenoids:|Introduction|Classification and structure|Physical and chemical properties|Extraction and isolat

2、ion|Identification|Structure elucidation|Crude drugs青蒿，穿心莲青蒿，穿心莲|Introdution:1.Definition:Terpenoids are regarded as derivatives of polymers of isoprene(异戊二烯异戊二烯),usually joined head to tail or tail to tail.The isoprene units arise biogenetically from mevalonic acid(MVA)and are branched-chain,five-c

3、arbon units containing two unsaturated bonds.甲戊二羟酸甲戊二羟酸异戊二烯异戊二烯Empirical isoprene rule2.Biosynthesis:Active isoprene活性异戊二烯活性异戊二烯Precursor 前体前体Condensation;Cyclization;Reduction;Dehydration脱氢脱氢;Decarboxylation脱羧脱羧焦磷酸异戊烯酯焦磷酸异戊烯酯焦磷酸焦磷酸r,r-二甲基烯丙酯二甲基烯丙酯Biogenetic isoprene rule3.Distribution:wide gymnospe

4、rm(裸子植物裸子植物)angiosperm(被子植物被子植物)fungi(菌类菌类)marine organisms(海洋生物海洋生物)4.Uses:Pharmaceuticals,perfumery,soaps,cosmetics,incense-sticks(熏香熏香),foods and beverage industries etc.Antiseptic(防腐防腐),stimulant,carminative(驱风驱风),diuretic(利尿利尿),analgesic etc.Insecticides(杀虫剂杀虫剂),deodorants(除臭剂除臭剂)5.Bioactivity：

5、（1）Circulation system：抗血小板聚集、扩张：抗血小板聚集、扩张心脑血管、降压、降脂等心脑血管、降压、降脂等芍药苷、银杏芍药苷、银杏内酯内酯（2）Digestive system：保保肝肝降降酶酶、利利胆胆健健胃胃、抗抗溃溃疡疡等等齐齐墩墩果果酸酸、甘甘草草次次酸酸、环环烯烯醚醚萜萜（3）Respiration system：平平喘喘、祛祛痰痰、镇镇咳咳等等穿心莲内酯穿心莲内酯、辣薄荷酮、辣薄荷酮（4）Nervous system：镇镇静静、局局麻麻、兴兴奋奋中中枢枢等等龙脑龙脑、高乌头碱、缬草环氧三酯、高乌头碱、缬草环氧三酯（5）Anti-tumour：紫紫杉杉醇醇、冬冬凌

6、凌草草素素、雷雷公公藤内酯藤内酯（6）抗生育：）抗生育：棉酚棉酚、芫花酯甲、乙、芫花酯甲、乙（7）Insecticide：青蒿素青蒿素、川楝素、川楝素（8）Spices：甜菊苷甜菊苷、香叶醇、香叶醇|Classification and structureThe basis for the classification:the number of isoprene unitsMonoterpenoids 2 C10H16 Sesquiterpenoids 3 C15H24Diterpenoids 4 C20H32Sesterterpenoids 5 C25H40Triterpenoids 6

7、C30H48Tetraterpenoids 8 C40H64Polyterpenoids n (C5H8)n The structural characters of terpenoids:with methyl with double bonds with oxygen Isoprene unit1.Monoterpenoids单萜：单萜：是是挥挥发发油油中中低低沸沸点点部部分分的的主主要要组组成成成成分分，其其含含氧氧衍衍生生物物多多具具有有较较强强的的生生物物活活性性及及香香气气，是是医医药药、化化妆妆品品和和食品等的重要原辅料。食品等的重要原辅料。acyclic无环无环 monocyc

8、lic单环单环(troponoids卓酚酮类卓酚酮类)bicyclic双环双环 iridoids环烯醚萜类环烯醚萜类Monoterpenoids:Acyclic Monocyclic Geranial Neral -thujaplicin Menthol Piperitone卓酚酮卓酚酮AromaticAcidicForm complex 柠檬醛主要存在于柠檬、山苍子油、柠檬醛主要存在于柠檬、山苍子油、香茅油、橘子油中，在乙醇钠作用下与香茅油、橘子油中，在乙醇钠作用下与丙酮缩合，得到丙酮缩合，得到紫罗兰酮及紫罗兰酮及-紫罗紫罗兰酮。兰酮。紫罗兰酮紫罗兰酮高级香料高级香料-紫罗兰酮紫罗兰酮合成

9、维生素合成维生素A 紫罗兰酮紫罗兰酮 -紫罗兰酮紫罗兰酮Bicyclic:偕烷偕烷蒎烷蒎烷莰烷莰烷守烷守烷芍药苷芍药苷龙脑龙脑樟脑樟脑茴香酮茴香酮Iridoids(环烯醚萜类环烯醚萜类)4-demethyliridoidsSecoiridoids(裂环环烯醚萜裂环环烯醚萜)catalpolGentiopicroside gentianine栀子苷栀子苷|环烯醚萜苷的理化性质环烯醚萜苷的理化性质1 1）多多为为白白色色结结晶晶或或无无定定形形粉粉末末，味味苦，有旋光。苦，有旋光。2 2）易易溶溶于于水水、甲甲醇醇，可可溶溶于于乙乙醇醇、丙酮等，难溶于亲脂性有机溶剂。丙酮等，难溶于亲脂性

10、有机溶剂。3 3）易易被被酸酸水水解解，生生成成的的苷苷元元因因具具有有半半缩缩醛醛(hemiacetal)结结构构，容容易易进进一一步步氧氧化化(oxidation)或或聚聚合合(polymerization)而而显显深深色色。中中药药地地黄黄、玄玄参参等等经经过过干干燥燥或或受受潮潮变变黑黑色，皆因该类成分水解氧化聚合。色，皆因该类成分水解氧化聚合。4）环环烯烯醚醚萜萜苷苷元元遇遇酸酸、碱碱、羰羰基基(carbonyl)化化合合物物、氨氨基基酸酸均均能能变变色。色。|环烯醚萜苷的提取分离环烯醚萜苷的提取分离环环烯烯醚醚萜萜苷苷类类亲亲水水性性较较强强，性性质质不不太太稳稳定定，

11、所所以以一一般般在在室室温温或或较较低低温温度度下提取。下提取。常常用用水水、甲甲醇醇、乙乙醇醇、稀稀丙丙酮酮等等作作溶溶剂剂，并并用用CaCO3或或Ba(OH)2抑抑制制酶酶的的活性并中和植物中的有机酸。活性并中和植物中的有机酸。怀庆地黄怀庆地黄甲醇回流提取甲醇回流提取减压回收甲醇减压回收甲醇甲醇浸膏甲醇浸膏水分散，正丁醇萃取水分散，正丁醇萃取水层水层正丁醇层正丁醇层减压浓缩减压浓缩乙醚溶解乙醚溶解不溶物不溶物（总环烯醚萜苷）（总环烯醚萜苷）总环烯醚萜苷总环烯醚萜苷活性炭、硅藻土混合柱层析活性炭、硅藻土混合柱层析 5%10%水洗水洗 1%乙醇洗乙醇洗乙醇洗乙醇洗水洗脱

12、液水洗脱液洗脱液洗脱液洗脱液洗脱液浓缩后浓缩后浓缩后浓缩后浓缩后浓缩后重结晶重结晶重结晶重结晶降糖活性降糖活性部位部位无色针晶无色针晶无色柱状晶无色柱状晶体体硅胶层析硅胶层析 (D-D-甘露糖）（蔗糖）甘露糖）（蔗糖）梓醇梓醇（0.110.11%）环烯醚萜苷的检识环烯醚萜苷的检识|与氨基酸共热产生深红色至与氨基酸共热产生深红色至蓝色，蓝色，最后生成蓝色沉淀；因此最后生成蓝色沉淀；因此与皮肤接与皮肤接触触,可使皮肤染成蓝色。可使皮肤染成蓝色。|于冰醋酸中加少量铜离子加热，产于冰醋酸中加少量铜离子加热，产生蓝色沉淀。生蓝色沉淀。|与酚类和胺类呈现各种颜色。与酚类和胺类呈现各

13、种颜色。2.倍半萜倍半萜Sesquiterpenoids:以烃、醇、酮、内酯等形式存以烃、醇、酮、内酯等形式存在，在，是挥发油中高沸点部分是挥发油中高沸点部分（250-280250-280）的主要组成成分）的主要组成成分。倍半萜的含氧衍生物多有较强的倍半萜的含氧衍生物多有较强的香气和生物活性。香气和生物活性。Sesquiterpenoids倍半萜倍半萜:Acyclic,monocyclic,bicyclic,tricyclic artemisinineudesmol atractylone青蒿素青蒿素奥类奥类azulenoids:由由五元五元环与环与七元七元环并合而成环并合而成的芳烃衍的芳烃衍

14、生物，具有一定的芳香性。生物，具有一定的芳香性。中药中所含的奥类成分多为其氢化物，中药中所含的奥类成分多为其氢化物，无芳香性。无芳香性。存存在在于于挥挥发发油油的的高高沸沸点点部部分分（bp250-bp250-300300），呈呈现现美美丽丽的的蓝蓝、紫紫或或绿绿色色，多多是是由由氢氢化化奥奥类类（如如愈愈创创木木醇醇类类）氧氧化化脱脱氢氢而而成成，能能溶溶于于石石油油醚醚、乙乙醚醚及及强强酸酸中中，不不溶溶于于水水。故故可可用用60-65%60-65%的的硫硫酸酸或或磷磷酸酸提提取取，稀稀释释后后即即可沉淀析出。可沉淀析出。curcumol愈创木醇愈创木醇|奥类的检识奥类的检识：Sabaty

15、Sabaty反反应应：1 1滴滴挥挥发发油油溶溶于于1ml1ml氯氯仿仿，加加入入5%5%溴溴的的氯氯仿仿液液数数滴滴，产产生生蓝蓝紫紫色或绿色时，表明含有奥类衍生物。色或绿色时，表明含有奥类衍生物。EhrlichEhrlich反反应应：与与对对二二甲甲氨氨基基苯苯甲甲醛醛-浓硫酸反应，为紫色或红色。浓硫酸反应，为紫色或红色。|生物活性：生物活性：奥奥类类衍衍生生物物广广泛泛存存在在于于愈愈创创木木油油、香香附附子子油油、桉桉叶叶油油、胡胡萝萝卜卜油油中中，多多具具有有抑抑菌菌、抗抗肿肿瘤瘤、杀杀虫虫等等活性，如莪术醇、泽兰苦内酯等。活性，如莪术醇、泽兰苦内酯等。3.Diterpenoids二

16、萜二萜:Acyclic,monocyclic,bicyclic,tricyclic,tetracyclicAndrographolides:Ginkgolides:Bicyclicditerpenoids左松脂酸左松脂酸松脂酸松脂酸松香酸松香酸TricyclicditerpenoidsTricyclicditerpenoidstaxolSteviosides:TricyclicditerpenoidsTetracyclicditerpenoidsTetracyclicditerpenoids|Sesterterpenoids二倍半萜：二倍半萜：Acyclic,monocyclic,bicy

17、clic,tricyclic,tetracyclic,pentacyclic|Physical Properties:Monoterpenoids and sesquiterpenoides:Colorless liquids or solids,insoluble in water,optically active,volatility and intensely pungent odors.They are the most common components in plants responsible for fragrance and flavor,abundantly availab

18、le in volatile oils.Diterpenoids:solids,bitter,rarely combined with sugars to form glycosides.(Stevioside甜菊苷甜菊苷 is an exception,300 times sweeter than sucrose蔗糖蔗糖)|Chemical properties:|Addition Reaction to the Carbon-Carbon Double Bonds双键加成双键加成:Addition of HCl;HBr;Br2;Cl-N=O(Tilden reagent)to produc

19、e crystals with color|Addition Reaction to the Carbonyl group（C=O）羰基加成）羰基加成:NaHSO3;Girard T or P亚亚硝硝酰酰氯氯反反应应：萜萜烯烯与与亚亚硝硝酰酰氯氯加加成成生生成蓝色或蓝绿色结晶性加成物。成蓝色或蓝绿色结晶性加成物。Diels-Alder反反应应：共共轭轭双双烯烯与与顺顺丁丁烯烯二二酸酐加成生成结晶性加成物。酸酐加成生成结晶性加成物。亚硝酰氯亚硝酰氯氯化亚硝基衍生物氯化亚硝基衍生物亚硝基胺类亚硝基胺类（蓝色或蓝绿色结晶）（蓝色或蓝绿色结晶）（物理常数一定的结晶）（物理常数一定的结晶）共轭双烯

20、共轭双烯单烯单烯Water solubleWater solubleWater insolubleTo do identification or isolation酮羰基酮羰基醛羰基醛羰基|Extraction and isolation:Extraction:Steam distillation Extract with solvent SFEIsolation:Seperated based on functional groups:C=C,C=O,COOH,-COO-,-NH-Crystallization Chromatographic methods SiO2;Al2O3 AgNO3

21、-SiO2;AgNO3-Al2O3提取分离实例：提取分离实例：|从独一味中分离环烯醚萜苷类从独一味中分离环烯醚萜苷类成分：成分：page 203|从圆叶泽兰中分离愈创木内酯从圆叶泽兰中分离愈创木内酯型双环倍半萜：型双环倍半萜：page 204|IdentificationReactions:Troponoides(卓酚酮类卓酚酮类):1%FeCl3 red;CuSO4 green Iridoids(环烯醚萜类环烯醚萜类):Trim-Hill reagent（醋酸、（醋酸、0.2%硫酸铜、浓硫酸铜、浓硫酸），硫酸），heat:blue red purple Shear reagent:yello

22、w,brown,dark green Azulenoids(奥类奥类):Sabety reagent(5%溴的氯仿溶液溴的氯仿溶液):blue,green,purple Ehrlich reagent(对二甲氨基苯甲醛对二甲氨基苯甲醛-浓硫酸试浓硫酸试剂剂):purple or redTLC spray reagents:|硫酸、茴香醛硫酸、茴香醛-浓硫酸、磷钼酸、浓硫酸、磷钼酸、碘等碘等|2，4-二硝基苯肼二硝基苯肼醛和酮醛和酮类（无环的显黄色，环状的显类（无环的显黄色，环状的显橙红色）橙红色）|对二甲氨基苯甲醛对二甲氨基苯甲醛奥类奥类（显蓝色）（显蓝色）通用通用显色剂显色剂专属专属显色剂显

24、 page137):It is the dried aerial part of Artemisia annua L.(Fam.Compositae)Actions:To remove summer-heat,relieve consumptive fever,and stop malarial attacks.Indications:Fever caused by summer-heat;afternoon fever in deficiency of Yin or in consumptive diseases;malaria with chills and fever;jaundice(

25、黄疸黄疸).|Chemical Constituents:青蒿素青蒿素蒿甲醚蒿甲醚青蒿琥酯青蒿琥酯双氢青蒿素双氢青蒿素artemisinin artemether artesunate dihydroartemisinin|Crude Drugs|穿心莲穿心莲 Herba Andrographis(CP2005 page189):It is the dried aerial part of Andrographis paniculata(Burm.f.)Nees.(Fam.Acanthaceae)Actions:To remove heat,counteract toxicity,and

26、 reduce swelling.Indications:Influenza with fever,sore throat,ulcers in the mouth or on the tongue;acute or chronic cough;colitis(肠炎肠炎),dysentery(痢疾痢疾);urinary infection with difficult painful urination;carbuncles(痈痈),sores,venomous(有毒的有毒的)snake bite.|Chemical Constituents:andrographolide dehydroand

27、rographolideExtraction and isolation：page 212Preparation of water soluble derivatives:page 213|赤芍赤芍来源来源毛茛科芍药或川赤芍的根。毛茛科芍药或川赤芍的根。功效功效清热凉血，散瘀止痛。清热凉血，散瘀止痛。成分成分单萜苷类单萜苷类：镇静、镇痛、抗炎：镇静、镇痛、抗炎芍药苷、氧化芍药苷、芍药芍药苷、氧化芍药苷、芍药内酯苷、苯甲酰芍药苷等。内酯苷、苯甲酰芍药苷等。鞣质、挥发油、甾类鞣质、挥发油、甾类等。等。|萜类小结：萜类小结：定定义义结结构与分构与分类类理化性理化性质质提取分离提取分离检识检识

28、萜萜类类单萜单萜倍半倍半萜萜二二萜萜二倍半二倍半萜萜卓酚卓酚酮类酮类环烯醚萜类环烯醚萜类奥奥类类柠柠檬檬醛醛、薄荷醇、薄荷醇、崖柏素崖柏素(卓酚卓酚酮酮)、紫紫罗兰酮罗兰酮、芍、芍药药苷、苷、樟樟脑脑、环烯醚环烯醚萜萜青蒿素青蒿素苍术酮苍术酮、棉酚、棉酚、莪莪术术醇醇(奥奥类类)VA、穿心、穿心莲莲内内酯酯、银银杏内杏内酯酯、雷公藤内雷公藤内酯酯、紫杉醇、紫杉醇甜菊苷、冬凌草素、甜菊苷、冬凌草素、巴豆醇巴豆醇AgNO3络络合合柱柱层层析析Volatile Oils:|Introduction|Chemical composition|Properties|Extraction and isol

29、ation|Identification|Crude drugs|IntroductionVolatile oils are the odorous volatile principals found in various plant parts.They can evaporate when exposed to the air at ordinary temperatures.They are immiscible with water.|Chemical Composition:Terpenoids derivatives (萜类萜类momo,sesquiterpenoids)Aroma

30、tic small molecule compounds (芳香族小分子芳香族小分子)Aliphatic small molecule compounds (脂肪族小分子脂肪族小分子)Others 水蒸汽蒸馏分解出的挥发性油状物：芥水蒸汽蒸馏分解出的挥发性油状物：芥子油、大蒜油子油、大蒜油|Properties:1.Colorless or light yellow oil 2.Characteristic odors,volatile 3.Optically active;Most of the densities of them are smaller than water 4.Immis

31、cible with water 5.Soluble in ether,alcohol and most organic solvents 6.Do not leave a permanent grease spot（油点）（油点）on paper 7.Unstable:oxidize and resinify（树（树脂化）脂化）Keep in brown vial with cap under low temperature|Extraction and isolationExtract:Steam distillation Solvent extraction SFE Others:exp

32、ression（压榨法）（压榨法）ecuelle method（组织破碎法）（组织破碎法）enfleurage method（油脂吸（油脂吸收法）收法）猪油、牛油猪油、牛油|Isolation:1.Crystallization at lower temperature2.Distillation:boilling points:ethersketonesaldehydesalcoholsestersacids 3.Chemical methods:page 218-219 alkaline constituents:1-2%HCl acidic compounds:5%NaHCO3;1-2%

33、NaOH ketones and aldehydes:30%NaHSO3;Girard T alcohols:phthalic anhydride(邻苯二甲酸酐邻苯二甲酸酐)4.Chromatographic method:2%AgNO3-SiO2;2%AgNO3-Al2O3挥发挥发油乙油乙醚醚溶液溶液1%HCl 萃取萃取乙乙醚层醚层酸水酸水层层碱化，乙碱化，乙醚醚萃取萃取乙乙醚层醚层回收乙回收乙醚醚碱性成分碱性成分水洗，水洗，5%NaHCO3 萃取萃取碱水碱水层层强强酸性成分酸性成分酸化酸化,乙乙醚醚萃取萃取乙乙醚层醚层1%NaOH萃取萃取碱水碱水层层乙乙醚层醚层弱酸性成分弱酸性成分Gi

34、rard水水层层乙乙醚层醚层酸化酸化,乙乙醚醚萃取萃取羰羰基化合物基化合物萜萜醇等中性成分醇等中性成分|For example：细辛：细辛：Chromatographic method:欧细辛醚欧细辛醚 -细辛醚细辛醚 -细辛醚细辛醚|Identification:1.Physical constants:relative density(相对密度相对密度)refrangibility(折光率折光率)optical rotation(旋光度旋光度)2.Chemical constants:acid number酸值酸值:neutralize KOH mg ester number酯值酯值:h

35、ydrolysis KOH mg saponification number皂化值皂化值:sum3.Functional groups:Legal reaction:lactones(亚硝酰铁氰化钠反应亚硝酰铁氰化钠反应)FeCl3:phenolsSabety reaction:unsaturated compounds and azulenoids奥类（奥类（Br2/CHCl3）Tollens test(Silver mirror):aldehydesGirard reagent:ketones and aldehydes4.Chromatography:TLC;GC;GC-MS Gas c

36、hromatography coupled with mass spectrometry(GC-MS)have led to the precise identification of the components of volatile oils,including trace constituents.|Crude Drugs|薄荷薄荷Herba Menthae(CP2005 Page261)Definition:Peppermint is the dried aerial part of Mentha haplocalyx Briq.(Fam.Labiatae唇形科唇形科)Actions

37、:To expel wind-heat from the head and eyes,and promote eruptions.Indications:Headache in fluenza,upper respiratory infection and other epidemic febrile diseases(流行性热病流行性热病)at the initial stage;inflammation of eyes,sore throat,ulcers in the mouth;rubella measles(荨麻疹荨麻疹);discomfort and distension in t

38、he chest and hypochondriac(胁胁)regions.|Chemical Constituents：Volatile oils:above 1%薄荷醇薄荷醇薄荷酮薄荷酮醋酸薄荷酯醋酸薄荷酯menthol menthone menthyl acetateChiral carbon23=8 isomers2 isomers are natural50%-85%Mainly are monoterpenoids（-）-薄荷醇薄荷醇（+）-新薄荷新薄荷醇醇|莪术莪术Rhizoma Curcumae(CP2005 Page194)Definition:Zedoray Rhizo

39、me is the dried rhizome of Curcuma phaeocaulis Valeton(蓬莪术蓬莪术),Curcuma kwangsinensis S.G.Lee et C.F.Liang(广西莪术广西莪术)or Curcuma wenyujin Y.H.Chen et C.Ling(温郁金温郁金).(Fam.Labiatae姜科姜科)Actions:To promote the flow of qi and eliminate blood stasis with strong effect,and relieve pain by removing the stagnat

40、ion of undigested food.Indications:Mass in the abdomen,amenorrhea due to blood stasis;distension(胀胀)and pain due to stagnation of undigested food;carcinoma of cervix(宫颈癌宫颈癌)at early stage.|Chemical Constituents：Volatile oils:1.0%-1.5%Active constituents:curcumol curdione|陈皮陈皮Pericarpium Citri Reticu

41、latae (CP2005 Page132)Definition:Dried Tangerine Peel is the dried pericarp of the ride fruit of Citrus reticulata Blanco橘橘 or its cultivars(栽培变种栽培变种).(Fam.Rutaceae芸香科芸香科)Actions:To regulate the flow of qi,invigorate the spleen function,eliminate damp,and resolve phlegm.Indications:Distension and fu

42、llness in the chest and epigastrium(上腹上腹)with anorexia(食欲不振食欲不振),vomiting and diarrhea;cough with copious phlegm(痰多痰多).|Chemical Constituents：广陈皮广陈皮(广东新会广东新会)Volatile oils:3.5%Above 80%柠檬烯柠檬烯 -桉油桉油烯烯 -月桂月桂烯烯-蒎烯蒎烯|挥发油小结：挥发油小结：定定义义化学化学组组成成理化性理化性质质提取分离提取分离检识检识挥挥发发油油萜类萜类芳香族小分子芳香族小分子脂肪族小分子脂肪族小分子其他其他物理常数物

43、理常数化学常数化学常数官能官能团团性状、性状、挥发挥发性、性、溶解性、物理常数、溶解性、物理常数、稳稳定性定性Page 218-219分离流程分离流程酸酸值值酯值酯值皂化皂化值值Summary|Terpenoids Definition Classification and important compounds Principle properties;Identification 青蒿、穿心莲、赤芍青蒿、穿心莲、赤芍|Volatile oils Definition Composition Principle properties Extraction and Isolation Identification 薄荷薄荷

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