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Stereoselective

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StereoselectiveStereo

    Stereoselective

ChineseChcmicalLettersVo1.14,No.2,PP130132,2003

    ;http://www.inln1.ac.cn/jounlal/cc1.html

    ;StereoselectiveSynthesisofsyn-andanti-3a-Hydi’oxyl-1,2,3,3a,8,

    ;8a.1lexahydropyrrolo2,3-bindole-2carboxylicAcid

    ;XiaoYinYANG,ChristianIIAUG2,

    ;YiPingYANG,ZhiShcngHYangYE

    ;StateKeyLaboratoryofDrugRcscarch,ShanghaiInstituteofMatcriaMcdica,ShanghaiInstitutes ;lbrBiologicalSciences.ChineseAcademyofScicncc,Shanghai20003l

    ;.Currentaddress:BicollBiotechnology(Shanghai)Co.Ltd.,518ABiboRoad,Shanghai201203 ;Abstract:TheSII’uctureol’?n—andantiNb.(tolucnesullbny1)3a.hydroxyl1,

    ;2,3,3a,8.

    ;8ahexahydropyrrolo[2,3bindote2

    carboxylicrbutylesterWaSstereoselectivelysynthesizedby

    ;oxidativeringlbl’lnationofNb_tolucnesulfony1)-Ltryptophalat-butyleStel.inmethylene

    ;chloridecontainingdi111cthyldioxirane(DMDO),theP-tolucnesulfonylgroupandt-butylgroupcan ;beeasilyremovedbysodiulnnaphthalelfideandtrilluoroaccticacid,respectively. ;Ke),ords:Oxidativeringlbrlnation.stcreoseleetivcsynthesis.sodiumnaphthalenide ;Alkaloidswith3ahydroxyl1,2,3,3a,8,8ahcxahydr0pyrro1o[2,3b]indole2

    ;carboxylicacid(HPI,A)substructurehavebccnisolatedfrombacteria,fungi,plantand ;mal’ineorganism.Thesenaturalproductsshowdiverscbiologicalactivities,e.g.ill

    ;antitumor,acyl—CoA(cholestel’o1acyltransfcrase)inhibition,neuropeptideand

    ;c11o1ccvstokininreceptorantagonisticinhibition.HPlisregardedastheirtoxophoric ;unit.Thustilesynthesisofthiskeysubstructurchasbeenattractintileinterestof ;organicchelnists.SOITIeproccdurcstowardstilesynthesis0fI_lPI1lavebeendeveloped. ;Howcvcrtheseproceduresarerelative1vcomplicatedandaby.product. ;N.f0m1V1kvnurcl1il1eB,wasusua11Yproducedj11theseprocedures.Recent1vthefirst ;diastcrcosc1cctiveappl’oachtothe.~’VI1andantiHP1scatfoldsusingtiledifferent

    ;configurationsofDandLtryptophaneasthestartingmaterialwasreported.Herein, ;wereportanewlyelaboratedsteroselectiverouteforthesynthesisofvn.andantiliPI ;byusingLtryptophaneassolestartingmateria1.

    ;6

    ;A

    ;yyc@mail.shcnc.ac.cn

    ;B

    ;2

    ;

    ;XiaoYinANGet”l

    ;0urresearchstartedfi’0111tilenaturallyabundantL-tryptophane1.

    ;P.Toluenesulfonyl-L-tryptophane2wassynthesizedsmoothlyfromL-tryptophanel

;refel’ringtOtileformerliterature.Compound3wasobtainedbytreating

    ;P-toluenesulfonyl-L-tryptophane2withN.N’-diisopropyl-O-fP,f-butylisoureawithout

    ;raccmizationunderincngas.Trcatnlentof3withN-bromosuecinimide(NBS)and ;t1’iethylaminegeneratedtheunstabledil1ydropyrroindolc5,whichcouldbcquickly

    ;purifiedbychrol11atographyonsilicage1.Subsequenttreatmentoflhiscompoundwith ;3.3.dimethy1.dioxirane(DMD0)at.78.Cfollowedbyreductionwithsodium ;borohydridelcdtothekeyintcrlnediate6substantiallyasasinglediastereomer(3aS, ;8aR)AccordingtOtile’H.NMRspectradatatheratioofdiastcrcomersiS41.2:2.7

    ;(.e.=88%,1.ThiSdiastereolnericCXCCSSCallbcenhancedbyapurifieationoverSillea ;eltod.e.>951.TilerelativeconfigurationwasdeterminedbyX-rayanalysisand ;l-I.NMR.’C.NMRThcS1?I1.compound4CallalsobccasilvobtainedbydiFeet

    ;oxidationof3withDMDOat78.Cin92%yieldandc.of72%.ThcconfigUl’ation

    ;of4wasdeterminedbycomparingofnmrdatawithcompound6(seeSchemel1. ;ItiSwcllknownthatthe,,.toluenesulfonylprotectinggroupattachedtOunaronlatic ;aminogroupiSquitedifficulttOberemoved.Inourapproach,sodiumnaphthalcnidcwas ;Schemel

    ;7

    ;Reagentsandconditions:(a)Ts-CI,NaHCO395%:(b)

    ;CHCI,85%:(C)NBS,EtN,91%:(d)DMDO,-78.C

    ;(nNaCI{)H,DME.65%:(g)Tl,CHCI.98%.

    ;8anti-HPl

    ;N,N’-diisopropyl-0-to!’,-butylisourca,dry

    ;(c)(i)DMDO..78.C.(ii)NaBH497%:

    ;

    ;l32StereoselectiveSynthesisofsynandanti-3aHydroxyl1,2,3,3a,8,

    ;8ahexahydropyrroIoI2,3bIindole2carboxylicAcid

    ;employedtocleavethisgrouptoyieldcompound7in65%withdin1ctl1oxycthanc(DME) ;assolvent6.

    ;Astotilef.butylpl’otcctinggroup,itisquiteeasytoremovequantitatively

    ;inthepresenceoftrifluoroaceticacidtoaflbrdtiletargetmolecular8(seeSchemeI,. ;Tilestructuresofcolnpound2,3,4,6,7andantiHPI8wereconfirmedby

    ;H.NMR.CNMR.ESIMS.

    ;Acknowledglnents

    ;WcaregratefullbrfinancialsupportsfromBaye~’AG,CompanyandNationalNaturalScience

    ;FoundationofChina(GrantNumber30123005).CHthankstheDAADforascholal’shipfromits

    ;pl’ogl’anl”Biowisscnschaflen”.

    ;ReferencesandNotes

    ;1.S.W.Pelletier,”Afdoid:Chenzi~?”fandBiologicafPer.s’1)ecti~,”,1)~rgamonVerlagOxl’d,

    ;l999,n.163.

    ;2.a)H.B.Arzeno,D.S.Kemp,SI?nthesis,l988,32.

    ;b)M.Nakagawa,S.Kato,S.Kodalo,H.Watanabe,H.Okajima,T.Hino,B.Witkop,~/Tem ;Phal’,.Bul1.1981.?9,l()l3.

    ;3.M.Nakagawa,YYokoyama,S.Kato,Hino,K’trahedmn,l985.40,2l25.

    ;4.T.M.Kamanecka,S.J.Danishel~ky,Chem.Elll:.,.2001.7,41.

;5.VD.Vigneaud,M.1Bal’tlett,U.D..Iohl,A,”Soc?.,l957.79,5572.

    ;6.C.H.Heathcock,A.Blumenkopf,K.M.Smith.0,Ch,”.,1989,,l548.

    ;7.Selecteddataofcompound6:Colorlessneedle,HNMR(CDCI,600MHz,6,):1.1()(s, ;9H,t-Bu),2.40(s,3H,1_s?CH),2.47(dd,lH,J=9.7Hz,J=l3.OHz,H3),2.69(dd,lH,J=l_3Hz, ;J=l3.()Hz,H3),4.33(dd,lH,-1=1.3Hz.J=9.7Hz.H.2),5.()()(s,lH,H.8a),6.62(d,lH,

    ;J=7.8Hz,H7).6.80(t,lH.J=7.8Hz,H5),7.18(m,2H,H4,6).7.36(d,2H,J=7.3Hz,Ts), ;7.8()(d,2H,J=7.3Hz,rs):”C—NMR(CDCI3,

    ;l00MHz,6):21.5(q,Ts?CH3),27.3(q×3,

    ;t-Bu),40.6(t,C3),6l,6(d,C2),81.8(s,C3a),83.5(d,C8a),87.6(s,,Bu),l0.8(d,C.7), ;l9.8(d,C?5),l23.8(d,C3b),l27.1(d×2,Ts),l28.5(s,Ts),l29.9(d×2,Ts),l31.1(d,C.6),

    ;l35.7(s,C.3b),l44.0(C.7a),l49.8(d,Ts),169.4(d,COO.,_Bu).ESlMSf,,7/):431.0(25%)

    ;fM+H453.1(100%)fM+Na

    ;ReceivedI9April,2002

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