5-2009-氫鍵誘導(dǎo)從芳酰胺基前體的一種大環(huán)化合物精準(zhǔn)合成方法(再看)

1、5-2009-氫鍵誘導(dǎo)從芳酰胺基前體的一種大環(huán)化合物精準(zhǔn)合成方法(再看) /obcDownloaded by University of Sussex on 21 January 2013 Published on 29 June 2009 on | doi:10.1039/B907457KVolume 7 | Number 16 | 21 August 2009 | Pages 31813344 ISSN 1477-0520FULL PAPERYuan-Yuan Zhu et al.A click chemistry approach for the synthesis of macrocy

2、cles from aryl amide-based precursors directed by hydrogen bonding PERSPECTIVEAndreas HerrmannDynamic mixtures and combinatorial libraries: imines as probes for molecular evolution at the interface between chemistry and biology Aclickchemistryapproachforthesynthesisofmacrocyclesfromaryl amide-basedp

3、recursorsdirectedbyhydrogenbonding? Yuan-YuanZhu,Gui-TaoWangandZhan-TingLi* Received14thApril2009,Accepted26thMay2009 FirstpublishedasanAdvanceArticleontheweb29thJune2009 DOI:10.1039/b907457k Thispaperdescribesthesynthesisoffourarylamide-basedmacrocyclesthroughthe1+1formationof two1,2,3-triazoleunit

4、sbyclickchemistry.Twoseriesofarylamide-basedprecursorsthatbeartwo azideoracetyleneunitshavebeenprepared.Intramolecularhydrogenbondinghas前驅(qū)體beenutilizedto inducethemtoadoptaU-styledconformation,whichremarkablypromotesthemacrocyclizationof twostructurallymatchedprecursors. Downloaded by University of

5、Sussex on 21 January 2013 Published on 29 June 2009 on | doi:10.1039/B907457KIntroductionInthepastdecade,thedevelopmentofnewapproachesforthesyn-thesisofshape-persistentmacrocycleshasreceivedconsiderable分子識(shí)別attentionduetotheirusefulnessinmolecularrecognition,sensing傳感和先進(jìn)材料1andadvancedmaterials.Onefam

6、ilyofsuchrigidarchitecturesconsistsofrepeatedorseparatedarylamidesegments,whichhavetraditionallybeensynthesizedstepwiseorbyone-step,multi-componentmacrocyclizations.2Recentadvancesinhydrogenbonding-drivenfoldamersofarylamide-basedbackboneshaveallowedforthedevelopmentofnewpreorganizedprecursorsorinte

7、rmediates,3whicharecapableofformingmacrocyclicproductsinremarkablyhighorevenquantitativeyields.4,5Withtheincreas-ingapplicationsof“click”chemistryinthesynthesisofdiscretemacrocyclicsystems,69webecameinterestedinconstructingwell-de?nedarylamide-basedmacrocyclesbymakinguseofthisapproach.Wehereinreport

8、thesynthesisandcharacterizationoffoursuchmacrocyclicmolecules,i.e.,14. Resultsanddiscussion Tosynthesizetheabovemacrocycles,wehavedesignedprecursors 510,whichbeartwoethynylorazidounits.Theiraromatic backboneshavebeenestablishedtoadoptthepreorganized U-shapedconformation,whicharestabilizedbyintramole

9、cular hydrogenbonding.10Theseframeworkshavebeenusedtoassemble離散severalmoleculartweezersforbindingdiscreteguests.11The azidomethylgroupis?exible,whichshouldavoidanylargetension generatedduetotheintramolecularhydrogenbondingforthe targetmolecules. Forthesynthesisofprecursor5(Scheme1),1110was?rst iodiz

10、edwithiodineinthepresenceofsilversulfateinethanolto give12quantitatively.Theesterwasthenhydrolyzedwithlithium hydroxidetogive13.With13beingavailable,1412wasreacted withiso-butanolintriethylaminetoafford15,13whichwasfurther StateKeyLaboratoryofBioorganicandNaturalProductsChemistry, ShanghaiInstituteo

11、fOrganicChemistry,345LinglingLu,Shanghai, 200032,China.E-mail:ztli;Fax:+862164166128; Tel:+862154925122 ?Electronicsupplementaryinformation(ESI)available:Synthesisand characterizationsand1HNMRspectraofselectedcompounds.SeeDOI: 10.1039/b907457khydrogenatedtogive16.Thisdiaminewasinstableintheairand,wi

12、thoutpuri?cation,reactedwithtwoequivoftheacylchlorideof13togivecompound17in95%yield.Palladium-catalyzedcou-plingof17withethynyltrimethylsilaneintriethylamineandTHFgenerated18in90%yield.Compound5wasthenobtainedin95%yieldbytreating18withtetrabutylammonium?uoride(TBAF)indichloromethaneandmethanol.The1+

13、1cycloadditionof5to1914inthepresenceofDIPEAandcupriciodideinchloroformwasthenperformed,whichgenerated1in20%yield. Org.Biomol.Chem.,2009,7,32433250|3243Thisjournalis?TheRoyalSocietyofChemistry2009 Downloaded by University of Sussex on 21 January 2013 Published on 29 June 2009 on | doi:10.1039/B907457

14、KThesyntheticroutefor6isshowninScheme2.Ester2011awas?rstpreparedaccordingtothereportedmethodandthenhydrolyzedwithsodiumhydroxidetogive21in95%yield.Theacidwasthencoupledwith16toproduce22in91%yield.Thisreactionneededalongtimebecauseiminederivativesmightalsobeformed,whichtooktimetobeconvertedtotheamide

15、duetoitsreversiblefeature.Thedialdehydewasthenreducedwithsodiumborohydridetodiol23in90%yield,whichwasfurthertreatedwiththionylchlorideat0?Ctogive24in95%yield.Finally,6waspreparedquantitativelyfromthereactionof24withsodiumazideinhotDMF.Themacrocyclizationreactionof5and6 inScheme1Reagentsandconditions

16、:(a)I2,Ag2SO4,EtOH,r.t.,3h,100%;(b)LiOHH2O,H2O/MeOH/THF,r.t.,12h,100%;(c)i-BuOH,Et3N,r.t.,12h,100%;(d)H2(60atm),Pd-C(10%),THF,6h,100%;(e)13,(COCl)2,DMF(cat),THF,30min;thenNEt3,THF,0?Ctor.t.,95%;(f)ethynyltrimethylsilane,PdCl2(PPh3)2,CuI,THF/Et3N,40?C,4h,90%;(g)t-Bu4NF,CH2Cl2,0.5h,95%.(h)CuI,DIPEA,CH

17、Cl3,r.t.,24h,20%.chloroforminthepresenceofDIPEAandcupriciodidewasthencarriedoutat10mMtogivecompound2in82%yield,whichisremarkablyhigherthanthatforcompound1,although1ismuchsmallerthan2.Thisresultclearlyillustratestheef?ciencyof the Scheme2Reagentsandconditions:(a)NaOH,THF/H2O/MeOH,r.t.,12h,95%;(b)16,C

18、lCO2Pr-i,Et3N,CHCl3,r.t.,24h,91%;(c)NaBH4,THF/MeOH,12h,90%;(d)SOCl2,CH2Cl2,0?C,2h,95%;(e)NaN3,DMF,80?C,4h,100%;(f)5,CuI,DIPEA,CHCl3,48h,82%.3244|Org.Biomol.Chem.,2009,7,32433250Thisjournalis?TheRoyalSocietyofChemistry2009 Downloaded by University of Sussex on 21 January 2013Published on 29 June 2009

19、 on | doi:10.1039/B907457K hydrogenbonding-inducedpreorganizationoftheprecursorsformacrocyclization. Encouragedbythehighyieldof2fromthereactionof5and6,wefurtherpreparedprecursors7and8.ThesyntheticroutesareshowninScheme3.Thepreparationof7startedfromtheiodationof25withiodineandsilversulfate,whichaffor

20、ded26in94%yield.Palladium-catalyzedcouplingof26withanexcessofethynyltrimethylsilanegave27quantitatively,whichwastreatedwithTBAFinTHFat0?Ctoyield28alsoquantitatively.Compound28wasthenselectivelyreducedto29withironandammoniumchlorideinre?uxingaqueoussolutionofethanolandTHF.Underthisreactioncondition,t

21、heethynylgroupwasnotreduced.Compound7wasthenobtainedin90%yieldbycoupling29with3013throughtherelateddiacylchloride.With7beingavailable,phenol3115wasreactedwithbutylbromidewithpotassiumcarbonateasbasetogive32in90%yield,whichwasreducedinTHFandmethanolbysodiumborohydrideto33in95%yield.Thisintermediatewa

22、sfurtherreducedwithironandammoniumchlorideinre?uxingaqueousethanoltoafford34quantitatively.Theanilinewasthencoupledwith30inDMFinthepresenceofHATUandDIPEAtodiol35in85%yield,whichwasthentreatedwiththionylchlorideinchloroformat 0?Ctoafford36in95%yield.Finally,compound8waspreparedquantitativelyfromthere

23、actionof36withsodiumazideinhotDMF.Compounds7and8(1:1,5mM)reactedinchloroformandacetonitrileinthepresenceofcupriciodideandDIPEAtoaffordmacrocycle3in85%yield.Thereactioncouldalsobecarriedoutinpurechloroformbuttookamuchlongertime.Acetonitrilemightfacilitatethereactionbyincreasingthesolubilityofcatalyst

24、cupriciodide.Theformationof3insuchahighyieldshouldagainbeattributedtothepreorganizationofthetwoprecursors. Toinvestigatethescopeofthisnewapproach,wealsopreparedtwoevenlargerprecursors9and10.Thesyntheticroutefor9isshowninScheme4.Thus,37was?rstpreparedin89%yieldfromthecouplingreactionof13and16.Thereac

25、tionconditionwasidenticaltothatforthepreparationof17,butthestartingmaterialswerecontrolledatthe1:1ratio.Inthisway,37couldbepreparedinhighyield,because37ismuchlessreactivethan16foracylation.Compound39wasthenpreparedin90%yieldbytreating37with3816inTHF.Thediiodidewasfurthercoupledwithethynyltrimethylsi

26、laneunderthecatalysisofpalladiuminTHFtoproduce40in95%yield,whichwasthentreatedwithTBAFinTHFtogive9in95% yield. Scheme3Reagentsandconditions:(a)I2,Ag2SO4,MeOH,re?ux,20h,94%;(b)ethynyltrimethylsilane,PdCl2(PPh3)2,CuI,THF/Et3N,r.t.,12h,100%;(c)TBAF,THF,0?C,5min,100%;(d)Fe,NH4Cl,EtOH/THF/H2O,re?ux,2h,10

27、0%;(e)(COCl)2,DMF(cat),THF,30min;thenEt3N,THF,0?Ctor.t.,90%;(f)n-C4H9Br,K2CO3,KI(cat),DMF,80?C,24h,90%;(g)NaBH4,THF/MeOH,r.t.,1h,95%;(h)Fe,NH4Cl,EtOH/H2O,re?ux,4h,100%;(i)30,HATU,DIPEA,DMF,r.t.,85%;(j)SOCl2,CHCl3,0?C,2h,95%;(k)NaN3,DMF,80?C,4h,100%.(l)CuI,DIPEA,CHCl3/CH3CN,24h,85%. Thisjournalis?The

28、RoyalSocietyofChemistry2009 Org.Biomol.Chem.,2009,7,32433250|3245 Downloaded by University of Sussex on 21 January 2013Published on 29 June 2009 on | doi:10.1039/B907457K Scheme4Reagentsandconditions:(a)(COCl)2,DMF(cat),THF,0?C,30min;thenEt3N,THF,0?Ctor.t.,2h,89%;(b)NEt3,THF,0?Ctor.t.,2h,90%;(c)ethy

29、nyltrimethylsilane,PdCl2(PPh3)2,CuI,NEt3,THF,40?C,12h,95%;(d)TBAF,THF,0?C,30min,95%. Forthesynthesisof10(Scheme5),42was?rstpreparedin95%yieldfromthereactionof41andn-butylbromideinhotDMFwithpotassiumcarbonateasbaseandthenhydrolyzedwithsodiumhydroxidetoacid43in95%yieldinaqueousmethanolandTHF.With43bei

30、ngavailable,compound44waspreparedin55%yieldbytreating38withtwoequivof16inTHFandfurthercoupledwith43,whichwasactivatedwithisopropylchloroformate,toproduce45in79%yield.Thedialdehydewasthenreducedwithsodiumborohydridetodiol46in95%yield,whichwasfurtherreactedwiththionylchloridetoafford47quantitatively.F

31、inally,treatmentof47withsodiumazideinDMFproduced10inquantitatively.Thereactionof9and10(1:1,5mM)wasthencarriedoutinchloroformandacetonitrileinthepresenceofcupriciodideandDIPEAtoaffordmacrocycle4in25%yield.Whenthereactionof47withsodiumazidewasperformedat80?CinDMFinthepresenceof1%water,compound10wasnot

32、obtained.Instead,thereactionafforded48exclusively.Thereactiondidnotoccurintheabsenceofsodiumazide,whichimpliedthatsodiumazidepromotedthehydrolysisoftheanisoleof47or10.Thereactionof48with9wasalsoperformedunderthereactionconditionusedforthepreparationof4.MALDI-FTmassspectrumdisplayedtheionpeakofthecor

33、respondingmacrocycle49.However,nopuresamplecouldbeseparatedduetothelowyield.Theresultagainshowstheimportanceoftheconformationalpreorganizationoftheprecursorsforthemacrocyclizations. preorganizationofaromaticamide-basedprecursors.Consideringthattriazole-basedmacrocyclesandfoldamersaregoodreceptorsfor

34、anions8,17andtheiranaloguesaregoodhydrogenbondingacceptors,thenewmacrocyclesmay?ndapplicationsinstudiesinmolecularrecognition.Comparedtothefullyhydrogenbondedmacrocycles,4,5thenewmacrocyclesconsistoftworigidsegmentswhichareconnectedwithtwo?exiblemethyleneunits.Thetworigidsegmentsofthesemacrocyclesma

35、yoscillateorfold.There-fore,theymayalsodisplaynewinterestingstackingproperties.18 Experimentalsection Unlessotherwiseindicated,allreactionswerecarriedoutunderanitrogenatmosphere.Startingmaterialswereobtainedfromcommercialsuppliersandusedwithoutfurtherpuri?cation.The1 HNMRspectrawererecordedon400or30

36、0MHzspectrometersintheindicatedsolvents.Chemicalshiftsareexpressedinpartspermillion(d)usingresidualsolventprotonsasinternalstandards(chloroform:d7.26ppm;DMSO:d2.49ppm).MALDI-TOFspectrawereobtainedonVoyager-DESTRorIonSpec4.7TeslaFTMSspectrometer.Compound12 Toasolutionof11(1.81g,8.70mmol)inethanol(45m

37、L)wereaddedsilversulfate(2.73g,8.70mmol)andiodine(2.21g,8.70mmol).Themixturewasthenstirredfor3handthenthesolid?lteredoff.The?ltratewasconcentratedunderreducedpressureandtheresultingslurrytrituratedwithAcOEt(30mL).Thesolutionwaswashedwithwater(30mL)andbrine(30mL)anddriedoversodiumsulfate.Afterthesolv

38、entwasremovedunder Thisjournalis?TheRoyalSocietyofChemistry2009 Conclusion Inconclusion,wehavedemonstratedthatmacrocyclicarchi-tecturescanbeconstructedinmodesttohighyieldsthroughclickchemistrybymakinguseofthehydrogenbonding-induced 3246|Org.Biomol.Chem.,2009,7,32433250 Downloaded by University of Su

39、ssex on 21 January 2013Published on 29 June 2009 on | doi:10.1039/B907457K Scheme5Reagentsandconditions:(a)n-C4H9Br,K2CO3,KI(cat),DMF,80?C,5h,95%;(b)NaOH,H2O/MeOH/THF,r.t.,12h,thenHCl,95%;(c)38,NEt3,THF,0?Ctor.t.,2h,55%;(d)ClCO2Pr-i,NEt3,CHCl3,r.t.,24h,79%;(e)NaBH4,MeOH/THF,r.t.,6h,95%;(f)SOCl2,CH2C

40、l2,0?C,2h,100%;(g)NaN3,DMF,r.t.,12h,100%;(h)CuI,DIPEA,CHCl3,CH3CN,24h, 25%. reducedpressure,theresultingresiduewassubjectedtocolumnchromatography(PE/EA,20:1)togive12asasolid(2.90g,100%).1 HNMR(CDCl3):d8.05(d,J=2.4Hz,1H),7.69(dd,J1=9.0Hz,J2=2.4Hz,1H),6.73(d,J=9.0Hz,1H),4.00(t,J=6.6Hz,2H),3.87(s,3H),1

41、.841.75(m,2H),1.571.44(m,2H),0.97(t,J=7.2Hz,3H).13CNMR(100MHz,CDCl3):d165.3,158.5,141.8,139.9,122.4,115.3,81.4,68.8,52.1,31.0,19.1,13.8.MS(ESI):m/z389.0M+K+.Anal.Calcd.forC12H15IO3:C,43.13;H,4.52.Found:C,43.44;H,4.67.Compound13 Asolutionof12(0.67g,2.00mmol)andlithiumhydroxidemonohydrate(0.17g,4.00mm

42、ol)inwater(10mL),THF(6mL)andmethanol(4mL)wasstirredfor12handthenconcentratedto10mL.Theresultingresiduewasacidi?edwithdilutedhydrochloricacid(5%)topH=3.Theformedprecipitatewas?ltratedoffandwashedwithcoldwatertogive13asawhitesolid(0.64g,100%).1HNMR(300MHz,CD3OD):d8.00(d,J=2.4Hz,1H),7.77(dd,J1=9.0Hz,J2

43、=2.4Hz,1H),6.94(d,J=9.0Hz,1H),4.08(t,J=6.3Hz,2H),1.861.77(m,2H), Thisjournalis?TheRoyalSocietyofChemistry2009 Org.Biomol.Chem.,2009,7,32433250|3247 1.611.49(m,2H),1.01(t,J=7.2Hz,3H).13CNMR(100MHz,CD3OD):d167.4,157.9,141.4,139.2,123.6,115.3,80.8,68.6,30.8,18.8,12.7.MS(ESI):m/z343.0M+Na+.Anal.Calcd.fo

44、rC11H13IO3:C,41.27;H,4.09.Found:C,41.34;H,4.00.Compound16 Asuspensionof15(0.62g,2.00mmol)andPd-C(60mg,10%)inTHF(30mL)wasstirredunder60atmofhydrogenfor12handthen?ltrated.The?ltratewasconcentratedtoaffordcompound16asayellowishoil,whichwasunstableinairandusedforthenextreactionwithoutfurtherpuri?cation.

45、 Downloaded by University of Sussex on 21 January 2013Published on 29 June 2009 on | doi:10.1039/B907457K water(15mL￥2)andbrine(15mL￥2),anddriedoversodiumsulfate.ThesolventwasthendistilledwitharotavaporandtheresultingresiduewashedwithcoldMeOHtoafford5asayellowishsolid(0.28g,95%).1HNMR(CDCl3):d9.75(s

46、,2H),9.18(s,1H),8.44(d,J=1.8Hz,2H),7.54(dd,J1=8.7Hz,J2=2.4Hz,2H),6.96(d,J=8.7Hz,2H),6.54(s,1H),4.21(t,J=7.2Hz,4H),3.79(d,J=6.6Hz,4H),3.01(s,2H),2.172.04(m,2H),1.92-1.82(m,4H),1.521.40(m,4H),1.01(d,J=6.3Hz,12H),0.95(t,J=7.5Hz,6H).13CNMR(CDCl3):d162.1,156.9,146.6,136.8,136.1,123.0,120.8,117.9,115.1,11

47、2.8,98.4,82.8,76.4,75.9,69.5,30.9,28.2,19.3,19.1,13.7.MS(MALDI-TOF):m/z675.1M+Na+.Anal.Calcd.forC40H48N2O6:C,73.59;H,7.41,N,4.29.Found:C,73.30;H,7.32;N,4.08.Compound1 Asuspensionof5(65mg,0.10mmol),19(19mg,0.10mmol),CuI(4mg,0.02mmol)andDIPEA(28mg,0.20mmol)inchloroform(10mL)wasstirredfor24h.Thesolidwa

48、s?ltratedoffandthe?ltrateconcentratedinvacuo.Theresultingresiduewassubjectedtocolumnchromatography(CH2Cl2/PE2:1)togive1asawhitesolid(17mg,20%)1HNMR(CDCl3):d9.17(s,2H),8.65(s,1H),8.29(s,2H),8.20(dd,J1=8.7Hz,J2=2.1Hz,2H),7.79(s,2H),7.44(s,4H),7.06(d,J=8.7Hz,2H),6.45(s,1H),5.60(s,4H),4.22(t,J=7.2Hz,4H)

49、,3.80(d,J=6.6Hz,4H),2.202.11(m,2H),2.16(s,2H),1.961.87(m,4H),1.561.42(m,4H),1.06(d,J=6.6Hz,12H),0.99(t,J=7.5Hz,6H).13CNMR(CDCl3):d164.7,155.7,147.8,147.4,134.9,131.3,130.0,129.0,123.7,123.3,119.6,112.8,97.6,75.5,69.1,53.9,30.9,28.2,19.3,19.0,13.8.MS(MALDI-TOF):m/z841.9M+H+.HRMS(MALDI-FT):Calcd.forC4

50、8H57N8O6:841.4396.Found:841.4370.Compound6 Asolutionof24(0.15g,0.20mmol)andsodiumazide(39mg,0.60mmol)inDMF(4mL)wasstirredat80?Cfor4handthenconcentratedwitharotavapor.Theresultingslurrywastrituratedwithchloroform(30mL)andthesolutionwashedwithwater(15mL￥3)andbrine(15mL)anddriedoversodiumsulfate.Uponre

51、movalofthesolvent,thecrudeproductwaspuri?edby?ashchromatography(PE/EA3:1)togive6asawhitesolid(0.15g,100%).1HNMR(CDCl3):d9.87(s,2H),9.28(s,1H),8.27(d,J=2.7Hz,2H),7.41(dd,J1=8.7Hz,J2=2.1Hz,2H),7.03(d,J=8.4Hz,2H),6.55(s,1H),4.34(s,4H),4.21(t,J=6.9Hz,4H),3.80(d,J=6.9Hz,4H),2.162.07(m,2H),1.941.85(m,4H),

52、1.471.29(m,8H),1.02(d,J=6.6Hz,12H),0.88(t,J=7.2Hz,6H).13CNMR(CDCl3):d162.5,156.7,146.2,132.7,132.4,128.2,123.0,121.0,117.3,113.4,98.3,75.9,69.8,54.1,28.6,28.3,27.9,22.3,19.2,13.9.MS(MALDI-TOF):m/z781.2M+K+.HRMS(MALDI-FT):Calcd.forC40H54N8O6NaM+Na+:765.4058.Found:765.4040.Compound2 Asuspensionof5(0.1

53、3g,0.20mmol),6(0.15g,0.20mmol),CuI(8mg,0.04mmol)andDIPEA(56mg,80mL,0.20mmol)inchloroform(20mL)wasstirredfor48handthenconcentratedwitharotavapor.Afterworkup,thecrudeproductwaspuri?edby?ashchromatography(CH2Cl2/EA1:3)togive2asawhitesolid(0.23g,82%).1HNMR(CDCl3):d10.04(s,2H),9.89(s,2H), Thisjournalis?T

54、heRoyalSocietyofChemistry2009 Compound17 Toasolutionof13(1.28g,4.00mmol)inTHF(10mL)andDMF(0.05mL)wasaddedoxalylchloride(1.60mL,20.0mmol)in30min.Thesolutionwasstirredfor30minandthenconcentrated.TheresultingresiduewasdissolvedinTHF(10mL).Tothissolution,cooledinanice-bath,wereaddedtriethylamine(0.60mL,

55、4.40mmol)andtheabovediamine16.Thesolutionwasstirredfor1hourandthenconcentratedunderreducedpressure.Theresultingresiduewaswashedwithmethanolthoroughlytogive17asayellowishsolid(1.63g,95%).1HNMR(CDCl3):d9.78(s,2H),9.24(s,1H),8.60(d,J=2.4Hz,2H),7.69(dd,J1=8.7Hz,J2=2.4Hz,2H),6.78(d,J=8.7Hz,2H),6.53(s,1H)

56、,4.18(t,J=6.9Hz,4H),3.79(d,J=6.9Hz,4H),2.152.06(m,2H),1.901.80(m,4H),1.511.41(m,4H),1.01(d,J=6.9Hz,12H),0.94(t,J=7.5Hz,6H).13CNMR(CDCl3):d161.5,156.5,146.3,141.2,141.0,124.9,120.8,117.5,115.2,98.3,83.7,75.8,69.6,30.8,28.3,19.3,19.0,13.8.MS(MALDI-TOF):m/z879.5M+Na+.Anal.Calcd.forC36H46I2N2O6:C,50.48;

57、H,5.41,N,3.27.Found:C,50.50;H,5.49;N,3.20.Compound18 Toasolutionof17(0.43g,0.50mmol),PdCl2(PPh3)2(37mg,0.05mmol)andCuI(11.5mg,0.05mmol)inTHF(10mL)andtriethylamine(5.00mL)wasaddedethynyltrimethylsilane(0.21g,1.50mmol).Thesolutionwasstirredat40?Cfor4handthenthesolid?ltratedoff.The?ltratewasconcentrate

58、dandtheresultingslurrytrituratedwithCH2Cl2(5mL).Thesolutionwaswashedwithwater(5mL)andbrine(5mL)anddriedoversodiumsulfate.Uponremovalofthesolvent,theresultingresiduewassubjectedtocolumnchromatography(PE/CH2Cl22:1)toafford18asawhitesolid(0.36g,90%).1HNMR(CDCl3):d9.74(s,1H),9.17(s,1H),8.43(d,J=2.4Hz,2H

59、),7.51(dd,J1=8.7Hz,J2=2.4Hz,2H),6.94(d,J=8.7Hz,2H),6.54(s,1H),4.20(t,J=6.6Hz,4H),3.79(d,J=6.6Hz,4H),2.152.06(m,2H),1.911.82(m,4H),1.521.40(m,4H),1.00(d,J=6.6Hz,12H),0.95(t,J=7.5Hz,6H),0.24(s,18H).13CNMR(CDCl3):d162.1,156.6,146.5,136.8,135.6,122.8,120.8,117.9,116.2,112.6,104.3,98.4,93.3,75.8,69.4,30.

60、8,28.2,19.2,19.0,13.7,-0.1.MS(MALDI-TOF):m/z797.8M+H+.Anal.Calcd.forC46H64N2O6Si2:C,69.31;H,8.09,N,3.51.Found:C,69.14;H,8.38;N,3.55.Compound5 Asolutionof18(0.36g,0.45mmol)andTBAF(0.13g,0.50mmol)inCH2Cl2(25mL)wasstirredfor30minandthenwashedwith 3248|Org.Biomol.Chem.,2009,7,32433250 9.53(br,2H),8.48(s