紫杉醇研究进展-沈征武

:19961,:199611*紫杉醇研究进展沈征武*　吴莲芬(中国科学院上海有机化学研究所　上海200032)紫杉醇是目前最新的具有很好疗效的抗癌药物,本文对自紫杉醇发现以来的最新研究进展进行了比较详尽的综述。包括以下几个部分:1.紫杉醇的发现和历史;2.紫杉醇的来源;3.紫杉醇的全合成研究;4.紫杉醇的生物合成;5.通过真菌生产紫杉醇;6.通过植物细胞培养生产紫杉醇;7.紫杉醇化学研究的展望。紫杉醇　综述AdvancesinTaxolResearchShenZhengwuWuLianfen(ShanghaiInstituteofOrganicChemistry,Shanghai200032,China)AbstractTherecentresearchadvancesontaxol,thenewestweaponsagainstcancer,havebeenreviewed.Theauthorsgiveanoverviewontaxolresearchfromthefollowingas-pects:1.Thehistoryoftaxoldevelopment;2.Sourcesoftaxol;3.Totalsynthesisoftaxol;4.Biosynthesisoftaxol;5.Taxolfromfungi;6.Taxolfromcallussystems;7.Perspectiveintaxolchemicalresearch.Keywordstaxol;review(taxol),1992FDA,,,,,,,,,baccatinIII(),,,,,,,301402000400069119973化　学　进　展PROGRESSINCHEMISTRYVol.9No.1Mar.,1997,6,30,1964,(RTI)MonroeWall,(Taxusbrevifolia)KB1969,Zemplen(1),(1)(2)X,(3)19712[1]12,,,,101979,SusanHorwitz[2],AB,,,vinblastinevincristine[3],,[4]19781982,[5][6]1983[7],[8],glucocorticoids,2化　学　进　展91985,,40,30%,[9]2556%,12%,44%FDA,,199510,,,baccatinIII10-deacetylbaccatinIII(10-DAB)1.FDA,,,cephalomannine(4)baccatinIII(5)(3)(),3Wheeler0.033%(w/w),0.01%(w/w)[10],,,T.brevifolia,baccatinIII0.2%10-deacetylbaccatinIIIT.bac-cata0.1%[11]CociancichT.mediaHicksiiT.mediaHill0.08%0.15%baccatinIII10-deacetylbaccatinIII0.02%0.06%0.03%0.08%4T.darkgreenspreadeer,,,[12]312.baccatinIIIbacctinIII10-deacetylbaccatinIII,baccatinIII,baccatinIII13,PotierbaccatinIII,Sharpless[13],,10-deacetylbaccatinIIITaxotere(6)(4)4Taxotere[14],PotierGreenebaccatinIII38%[15]HoltonBbaccatin,[16](5),Commercon,Ojima[1720]5(1)BaccatinIII10-deacetylbaccatinIII,baccatin6(2)Taxotere40:(1),AABCCABC(2),ACABC(6)BoaNicolaou[21],,1994,HoltonNicolaou[22,23]?A/B/C(D,AC154化　学　进　展96742kJ/molBB51,DC7,B,HoltonAABC(7),9,9B,CC7AldolChanDieckmannC,1212C13bac-catinIII,,(7)Nicolaou[23](8),Diels-AldolA,202017Funk,82%AC2117Diels-Aldol21C14,C9C10McMurry-Pinacol20%(22)22D,8,,Nicolaou,(0.07%)Holton(2.7%)Nicolaou,McMurry,,HoltonNicolaou,6化　学　进　展9,Wender,[24](1)(2),,,,(3)(4),,,,,(geranylgeranyldiphosphate),,,,,,H.G.Floss[2527],B,2,(9)taxa-4(20),11(12)-diene,(10)10,,Phloemparenchyma,[28,29],[30,31],Mg2+1-3H(1%),LCi,10%,10-DAB,baccatinIII,cephalomaninetaxadiene[3234]taxa-4(5),11(12)-diene,71910taxa-4(5),11(12)-dienetaxa-4(20),11(12)-diene,(1111)A,1S-verticillene7,5taxadieneverticillene,,T.cuspidataT.brevifolia,[35]T.canadensis,T.floridanaT.brevifolia,T.bre-vifolia[36],(taxadienecyclase),(taxadieneoxygenase)[37,38],,8化　学　进　展9,,,,,,,,:(1),;(2);(3)[39,40],;(4)1993,GaryStrobel[41,42],,2450ng/L,,,1989,[43]PhytonCatalytic13mg1991,25[44],,,[45]ESCAGenetics[44],,,,,T.cuspidataT.canadensT.cuspidata0.02%T.cuspidata,0.012%[46],,[47]FrankDicosmoT.cuspidata,T.cuspidata172091,(0.4Lg/ml),(0.1Lg/ml)[48],,0.002%0.01%[49]ESCAGeneticsSmithRichard,,(1)1(,%)(,%)T.baccata0.000094T.baccataRepandens()0.00006T.baccataresemblingHessei()0.0003T.canadensis0.00007T.canadensis()0.00054T.canadensis()0.00046T.chinensis()0.00443T.chinensis()0.00494T.cuspidata()0.00095T.cuspidata()0.0008T.cuspidataColumaris()0.00015T.floridana()0.00037T.floridana()0.00025T.globosa0.00017T.hunnewelliana()0.00081T.Irishyew0.0013Torreyataxiforlia()0.00022T.x.mediaBrevicata0.00151T.x.mediaBrevimedia()0.00131T.x.mediaDensiformis()0.00046T.x.mediaHicksii()0.00008T.x.mediaHicksii()0.0011T.x.mediaHicksii0.00079T.x.mediaKelseyi0.0007T.x.mediaMaureen0.00029,(T.chinensis),,,0.06%[50]T.brevifolia0.05%()[51]PhytonCatalyticT.chinensis0.533%,0.098%[52],,,[53]1.4,;,;,,;,,10-DAB,baccatinIII,14-hydroxytaxoidsA-nor-tax-ols[54],,,,10化　学　进　展92.1989,2,4,5,7,9,1014[5559](1)C2C3C32R,3S(2)7,8,9,104(3)2,4,524,4,5-,,[1]WaniMC,TaylorHL,WallME,CoggonP,McPhailAT,J.Am.Chem.Soc.,1971,93,23252327.[2]SchiffPB,FantJ,HorwitzSB,Nature,1979,277,665667.[3]NeussN,NeussMN,inTheAlkaloids,Vol.37(eds.BrossiA,SuffnessM),AcademicPress,NewYork,NY,1990,229239.[4]ParnessJ,HorwitzSB,J.Cell.Biol.,1981,91,479481.[5]NationalCancerInstitute,DivisionofCancerTreatment,Taxol(IND22850,NSC1259730,Annu.Rep.toFDA),March,1991.[6]SuffnessM,CordellGA,inTheAlkaloids,Vol25(ed.BrossiA),AcademicPress,NewYork,NY,1985,1369.[7]HolmesFA,WaltersRS,TheriaultRL,FormanAD,NewtonLK,RaberMN,BuzdarAU,FryeDK,HortobagyiGN,J.Natl.CancerInst.,1991,83,17971805.[8]KrisMS,OConnellJP,GrallaRJ,WertheimMS,ParenteRM,SchiffPB,YoungCW,CancerTreat.Rep.,1986,70,605607.[9]McGuireWP,RowinskyEK,RosensheinNB,GrumbineFC,EttingerDS,ArmstrongDK,DonehowerRC,Ann.InternalMed.,1989,111,273.[10]WheelerNC,JechK,MastersS,BrobstSW,AlvaradoAB,HooverAJ,SnaderKM,J.Nat.Prod.,1992,55,432440.[11]CgauviereG,GuenardD,PicotFetal.,AnalyseStructuraleetEtudeBiochimiquedeProduitsIsolesdeI'lf:TaxusBaccataL.(Taxacees),C.R.Acad.Sci.Paris,Series,1981,293,501.[12]CociancichErmanno,EuropeanPatentApplication,EP0553780A1,1993.[13]MangatalL,AdelineM-T,GreeneAE,GuenardD,Gueritte-VoegeleinF,PotierP,Tetrahedron,1111989,45,41774190.[14]Gueritte-VoegeleinF,GuenardD,LavelleF,LegoffM-T,MangatalL,PotierP,J.Med.Chem.,1991,34,992998.[15]DenisJ-N,GreeneAE,GuenardD,Gueritte-VoegeleinF,MangatalL,PotierP,J.Am.Chem.Soc.,1988,11