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1、SynthesisofObyanamide,aMarineCytotoxicCyclicDepsipeptideChineseChemicalLettersVol,17,No,3,PP285—288,2006http://www,imm,ac.cn/journaYccl,html285SynthesisofObyanamide,aMarineCytotoxicCyclicDepsipeptideWeiZHANG,NiSONG,ZhongZhenLI,YingXiaLIKeyLaboratoryofMarineDrugs,theMin
2、istryofEducationofChina,MarineDrugandFoodInstitute,OceanUniversityofChina,Qingdao266003Abstract:Thesynthesisofamarinecytotoxiccyclicdepsipeptideobyanamidehasbeenaccomplished,ThekeystepsincludeassemblinglinerpentapeptideviaYamaguchiesterificationandHATU?promotedringclos
3、ing.ThestructureofthesyntheticsamplewasidentifiedbyHand"CNMR,H-HCOSYHMQC,HMBC,andHRESIMS.butappearstobedifferentfromthatofthemarinenaturalproduct.Keywords:Obyanamide,synthesis,cyclicdepsipepfide,naturalproduct,Obyanamide1isacyclicdepsipeptidethatwasrecentlyisolatedfrom
4、themarinecyanobacteriumLyngbyaconfervoidesbyMooreandCO—WOrkers.ThiscompounddisplayedapotentinhibitoryeffectonbOmI(BandLoVocellsinvitro.SeveralstructuralanalogshavealSObeenisolatedlater,namelyulongamideA—EandguineamideA—B'.TheyallincludehighdegreeofN—methylated0【.aminoa
5、cids,0c—hydroxyacids,B—aminoacids,andcysteinederivedthiazolerings.Currentresearchresultssuggestedtllattheircytotoxicitiesalehighlydependentontheprimarystructures.Toinitiatetheirstructure—activityrelationship(SAR)studies,wedecidedtoexploreanefficientproceduretosynthesiz
6、ethesecompounds,Herewereportthesynthesisofobyanamide,andoBrretrosyntheticanalysiswasalSOdisplayedasFigure1.Figure1Structureandretrosyntheticanalysisofobyanamide1E—mail:liyx417@ouc.edu.caIOrBuBocHN~-IS+.HN.oH,o儿人/32286NHRHoWeiZHANGelalScheme1Synthesisofdipeptide2ONHBoc
7、.o/u人/Bo(3HN5^N—c∞Ef___js,JJ2-24Reagentsandconditions:(a)(Boc)20,91.0%;(b)C1COOEt,Et3N,thenCH2N2;(c)AgOAc,MeOH,61-3%for2steps;(d)TFA,CH2C12;(e)LiOH,THF/MeOH/H20;(f)EDC,HOAt,DIPEA,CH2C12.98.0%for3stepsindevisingasyntheticschemeforobyanamide,themostimportantstepsarethe
8、constructionofnonnaturalaminoacidsandtheformationofhinderedpeptidebonds.Fortunately,thenonaturalaminoacidresiduesinob
