青蒿素研究进展

　:199712,:19984*青蒿素研究进展刘春朝　王玉春*　欧阳藩(中国科学院化工冶金研究所生化工程国家重点实验室　北京100080)叶和春　李国风(中国科学院植物研究所　北京100093)　　青蒿素是目前治疗疟疾的特效药。本文对自青蒿素发现以来的最新研究进展进行了比较详尽的综述。内容包括:青蒿素的发现及历史,青蒿素的来源,青蒿素的全合成,青蒿素的生物合成,青蒿素衍生物以及植物组织培养生产青蒿素。　青蒿素　青蒿素衍生物　合成AdvancesinArtemisininResearchLiuChunzhao　WangYuchun　OuyangFan(StateKeyLaboratoryofBiochemicalEngineering,InstituteofChemicalMetallurgy,ChineseAcademyofSciences,Beijing100080,China)YeHechun　LiGuofeng(InstituteofBotany,ChineseAcademyofSciences,Beijing100093,China)Abstract　Therecentresearchadvancesinartemisinin,themosteffectiveweaponsagainstmalarialparasiteshavebeenreviewed.Anoverviewisgivenonartemisininresearchfromthefollowingaspects:thehistoryofartemisinindevelopment,sourcesofartemisinin,totalsynthesisofartemisinin,biosynthesisofartemisinin,analogsofartemisininandartemisininproductionfromplanttissuecultures.Keywords　artemisinin;artemisininderivatives;synthesis(artemisinin)、、,,[1]。,-[2,3],,。(ArtemisiaannuaL.)。、,,,,,,,,。,,11119992化　学　进　展PROGRESSINCHEMISTRYVol.11No.1Feb.,1999,。,225/g。300,,,150,15,,“”。。1.,(168)《》,《》,《》《》。,。1971,,,。,1972——,1976、X,C15H22O5,1[4],[5]。1　,,,。,,,。,8h,,12—14h、,20—24h,。,,-,[6]。,。19739,,8,。1975、、,。1976、1977、、4,。、、,,。,,、、[7]。,。,,。2.,。,。。·42·化　学　进　展11、、、。,,1%—2%。,[8],,,,1216,,。,、、。,,,。,、60℃,,23.76%。,,,。[9],,,。Elhag[10],,,。Liersch[11]811chlormequat,30%。,,。,,,,。3.2　·43·1　　　。[12-18]。1986,Xu[19],R(+)-,,2。[20-23]。1994,ZhouXu[24]。,。4.。:(1);(2),;(3)。,。,,。Akhila[25],3,,(germacrane)、(dihydrocostunodile)、(cardinanolide)B(arteannuinB),。,[2-14C]-MVA[26],B[27]。3　5.,,,,。,,12。[28],12,,,。[29](I)(II),,、,(III)、(IV)(V)47,4。,SD90,10·44·化　学　进　展114　12。,。,、,,、、、、27,500[30]。6.,。80,,、、。[31]、,,,0.008%,,0.92%,。Nair[32],,(8μg/mL)。Brown[33],。Tawfit[34],,。Paniego[35]0.1%—0.08%,,。,,。Woerdenbag[36],,。Ferreira[37],,,0.287%。Paniego[38],,0.02%,,3—4。1994,[39]1601,。,Weathers[40]15834,,0.43%,。[41]1601,,0.2%。Vergauwe[42],0.17%,B0.22%,·45·1　。,,。Fulzele[43]1L,30,4—5。Park[44]2L,4,8,。,“”,[45],[46],,。,(),,;(、),,,。,,:(1),;(2);(3);(4),;(5),,。[1]KlaymanDL,Science,1985,228,1049—1055.[2]DaviesEE,Ann.Trop.Med.Parasit.,1975,69,147—154.[3]TheakstonRDG,LifeSci.,1969,8,521—529.[4](ResearchGroupofArtemisininStructure),科学通报(ChineseSci.Bull.),1977,22,142.[5](LiuJM),(NiMY),(FanJF),(TuYY),(WuZH),(WuYL),(ZhouWS),化学学报(ActaChim.Sinica),1979,37,129—141.[6](ResearchGroupofArtemisininStructure),药学通报(ChinesePharm.Bull.),1979,14,49—53.[7](LiY),(YuPL),(ChenYX),(LiLQ),(GaiYZ),(WangDS),(ZhengYP),科学通报(ChineseSci.Bull.),1979,24,667—669.[8](ZhongFL),(ChenHR),(ChenM),中国中药杂志(ChinaJournalofChineseMateriaMedica),1997,22,405—406.[9](ChenFT),(ZhangGH),植物生理学通讯(PlantPhysiologyCommunications),1987,5,26—30.[10]ElhagHM,PhytotherapyResearch,1992,6,20—24.[11]LierschR,PlantaMed.,1986,5,387—390.[12](XuXX),(ZhuJ),(HuangDZ),(ZhouWS),化学学报(ActaChim.Sinica),1983,41,574—575.[13](XuXX),(ZhuJ),(ZhangL),(ZhouWS),化学学报(ActaChim.·46·化　学　进　展11Sinica),1989,47,771—774.[14](ZhangL),(ZhouWS),化学学报(ActaChim.Sinica),1989,47,1117—1119.[15](XuXX),(WuZH),(ShenJM),(ChenZH),(WuYL),(ZhouWS),化学学报(ActaChim.Sinica),1984,42,333—339.[16](ZhouWS),(HuangDZ),(PingXF),(ZhangL),(ZhuJ),(XuXX),化学学报(ActaChim.Sinica),1989,47,710—715.[17](ZhuJ),(XuXX),(ZhouWS),化学学报(ActaChim.Sinica),1987,45,150—153.[18](ZhouWS),(XuSJ),(ZhangL),化学学报(ActaChim.Sinica),1989,47,340—344.[19]XuXX,ZhuJ,HuangDZ,ZhouWS,Tetrahedron,1986,42,819—828.[20]AveryMA,ChongWKM,Jennings-WhiteC,J.Am.Chem.Soc.,1992,114,974—979.[21]AveryMA,Jennings-WhiteC,ChongWKM,TetrahdronLett.,1987,28,4629—4632.[22]RavindranathanT,AnilKumarM,MenonR,HiremathSV,TetrahdronLett.,1990,31,755—758.[23]SchmidG,HofheinzW,J.Am.Chem.Soc.,1983,105,624—625.[24]ZhouWS,XuXX,Acc.Chem.Res.,1994,27,211—216.[25]AkhilaA,ThakurRS,PopliSP,Phytochemistry,1987,33,1927—1930.[26](HuangJJ),(ZhouFY),(WuLF),(ZengGH),化学学报(ActaChim.Sinica),1990,48,275—277.[27](WangY),(XiaZQ),(ZhouFY),(WuYL),(HuangJJ),(WangZZ),化学学报(ActaChim.Sinica),1988,46,1152—1153.[28](LiangJ),(LiY),中国药物化学杂志(ChineseJournalofMedicinalChemistry),1996,19,22—25.[29](LiY),(YuPL),(ChenYX),(LiLQ),(GaiYZ),(WangDS),(ZhengYP),药学学报(ActaPharm.Sinica),1981,6,429—439.[30](WangCZ),(PuCD),中草药(ChineseHerbalMedicine),1996,27,253.[31](HeXC),(ZengMY),(LiGF),(LiangZ),植物学报(ActaBotanicaSinica),1983,25,87—90.[32]NairMSR,ActonN,KlaymanDL,KendricK,BasileDV,ManteS,J.Nat.Prod.,1983,49,504—507.[33]BrownGD,J.Nat.Prod.,1994,57,975—977.[34]TawfiqNK,AndersonLA,RobertsMF,PhillipsonJD,BrayDH,WarhurstDC,PlantCellRep.,1989,8,425—428.[35]PaniegoNB,GiuliettiAM,PlantCellTiss.Org.Cult.,1994,36,163—168.[36]WoerdenbagHJ,JosFJ,WinvanUden,NieskoPras,MalingreTM,AlfermannAW,PlantCellTiss.Org.Cult.,1993,32,247—257.[37]FerreiraJFS,JanickJ,PlantCellTiss.Org.Cult.,1996,44,211—217.[38]PaniegoNB,GiuliettiAM,EnzymeMicro.Tech.,1996,18,526—530.[39](QinMB),(LiGZ),(YunY),(YeHC),(LiGF),植物学报(ActaBotanicaSinica),1994,36,165—170.[40]WeathersPJ,CheethamRD,FollansbeeE,TeohK,Biotechnol.Lett.,1994,16,1281—1286.[41](CaiGQ),(LiGZ),(YeHC),(LiGF),生物工程学报(Chinese·47·1　JournalofBiotechnology),1995,11,315—320.[42]VergauweA,CammaertR,VandenbergheD,GenetelloC,InzeD,MontaguMV,EeckhoutEV,PlantCellRe