Solvent- and Catalyst-free Synthesis and Antifungal Activities of α-Aminophosphonate Containin

SynthesisandAnti-HelicobacterpyloriActivityof

4-(Coumarin-3-yl)thiazol-2-ylhydrazoneDerivatives

FrancoChimenti,aBrunaBizzarri,a*AdrianaBolasco,aDanielaSecci,a

PaolaChimenti,aAriannaGranese,aSimoneCarradori,aMelissaD’Ascenzio,a

M.MaddalenaScaltrito,bandFrancescaSistob

aDipartimentodiChimicaeTecnologiedelFarmaco,University‘‘LaSapienza,’’P.leA.Moro5,00185Rome,ItalybDipartimentodiSanita`Pubblica-Microbiologia-Virologia,Universita`degliStudidiMilano,viaPascal36,20133Milan,Italy*E-mail:zarri@uniroma1.itReceivedJanuary13,2010DOI10.1002/jhet.464Publishedonline20August2010inWileyOnlineLibrary().

Anovelclassofcoumarin-thiazoleconjugatedsystems(1–31)weresynthesizedbyHantzschconden-

sationbetweena-bromo-3-acetylcoumarinandseveralthiosemicarbazoneintermediates.Thisscaffold

wasalsoevaluatedforselectiveantibacterialactivityagainst20isolatesofH.pyloriclinicalstrains,

NewsialylLewisxmimiccontainingana-substituted

b3-aminoacidspacer

SilvanaPedatella,a,*MauroDeNisco,aBeatErnst,bAnnalisaGuaragna,a

BeatriceWagner,bRobertJ.WoodscandGiovanniPalumboa

aDipartimentodiChimicaOrganicaeBiochimica,Universita`diNapoliFedericoII,ViaCynthia,4I-80126Napoli,ItalybInstituteofMolecularPharmacy,Pharmacenter,UniversityofBasel,Klingelberstrasse,50CH-4056Basel,SwitzerlandcComplexCarbohydrateResearchCenter,UniversityofGeorgia,315RiverbendRoad,Athens,GA30602,USA

Received11June2007;receivedinrevisedform20August2007;accepted2October2007Availableonline7October2007

Abstract—AhighlyconvergentandefficientsynthesisofanewsialylLewisx(sLex)mimic,whichwaspredictedbycomputationalstudiestofulfilthespacialrequirementsforaselectinantagonist,hasbeendeveloped.Withab2,3-aminoacidresidueL-galactose(bioisostereoftheL-fucosemoietypresentinthenaturalsLex)andsuccinatearelinked,leadingtoamimicofsLexthatcontainsalltherequiredpharmacophores,namelythe3-and4-hydroxygroupofL-fucose,the4-and6-hydroxygroupofD-galactoseandthecarboxylicacidofN-acetylneuraminicacid.ThekeystepofthesynthesisinvolvesatandemreactionconsistingofaN-deprotectionandasuitableO!Nintramolecularacylmigrationreactionwhichispromotedbyceriumammoniumnitrate(CAN).Finally,thenewsialylLewisxmimicwasbiologicallyevaluatedinacompetitivebindingassay.Ó2007ElsevierLtd.Allrightsreserved.

CatalyticEnantioselectivePudovikReactionofAldehydesandAldimineswithTetheredBis(8-quinolinato)(TBOx)AluminumComplex

JoshuaP.AbellandHisashiYamamoto*

DepartmentofChemistry,TheUniVersityofChicago,5735SouthEllisAVenue,Chicago,Illinois60637

ReceivedMay22,2008;E-mail:yamamoto@

TheadditionofdialkylphosphitestocarbonylcompoundstogenerateR-hydroxyphosphonates,knownasthePudovikreaction,isapowerfulanddirectmethodforconstructionofC-Pbonds.Withthepotentialtosynthesizebiologicallyimportantphospho-derivativesofR-hydroxycarboxylicacids,thisreactionhasreceiveddeservedattentionlatelytomaketheprocesshighlyenantioselective.1TodateseveralorganocatalystsincludingCinchonaalkaloids2andchiralphosphoricacids,3Lewisacidsincludingtitanium,4latetransitionmetals,5aluminum6aSALALEN,6bSALEN,7SALAN,7BINOL,8andchiralvanadiumcatalyst9havebeenutilizedforthisreaction.Unfortunately,thesecatalyststypicallyrequirehighcatalystloadingandlongreactiontimes,usuallyg5mol%orgreaterandseveraldays.Duetotherecentsuccessusingtheligand1developedinourlaboratory,10weenvisagedthatourligand,whencomplexedwithaluminum,couldprovetobeahighlyselectiveandactivecatalystforthePudovikreaction.Withthechiraltetheredbis(8-quinolinato)(TBOxH)ligandinhand,complexationtookplacesmoothlyatroomtemperaturebyadditionofasolutionofEt2AlCl(Scheme1).Thiscatalyst2wasusedunderpreviouslyreportedconditions;however,onlylowyieldsandenantioselectivitieswereobserved(Table1,entries1-4).Withthesepositiveresultswesetouttofindamorereactivesystem.Whiletheactualmechanismhasnotbeenexperimentallyconfirmed,itisbelievedthatthefirststepisdeprotonationofthephosphitetogenerateamorehighlynucleophilicspecies.1dTheprotononthephosphitewasfoundtobecrucialfortheenantioselectivityofthereaction.11Usingamoreelectronwithdrawingalkylgrouponthephosphitetheyieldcouldbeimprovedtosyntheticallyusefullevels.AsshowninTable1,thebis(2,2,2-trifluoroethyl)phosphiteincreasedtheyieldto94%andtheenantioselectivityto48%(entry5).12Witheffortsnowfocusedonincreasingtheenantioselectivity,increasingthesizeofthealkylgrouponlydecreasedtheyieldandselectivity(entry6),possiblyduetodecreasednucleophilicityofthephosphiteandincreasedstericenvironment.Decreasingthereactiontemperatureonlydecreasedthereactivitywhilenotincreasingtheenantioselectivity(entry7).Interestingly,afterscreeningthereactionconditions,decreasingthecatalystloadingofthereactionincreasedtheenantioselectivitywhilemaintainingthesamereactivityandyield(entry8).ThisphenomenonwasalsoobservedwiththeworkofNorthintheenantioselectivesilylcyanationreaction13andmorecloselyrelatedwithKee’shydrophosphonylationreaction.7Furthermore,itwasfoundthatnonpolarsolventsgavehigherenantioselectivity,withhexanesgivingthehighestreactivityandselectivity(entry9).Withtheinfluenceofthephosphiteandsolventnowestab-lished,theligandstructurewasexamined(Table2).Theligandstructurewasfoundtobehighlyinfluentialontheenantiose-lectivityoftheproduct.Simplyattachingaphenylsubstituentatthe5,5′-positionofthequinolineringledtoadramaticincreaseinenantioselectivity(entry2).Pleasedwiththisresultwefurtherexaminedotherderivativesandfoundcatalysts4and5tobemostreactiveandselective(entries3and4).Sincetherewasnochangeinyieldandenantioselectivitesofthemostselectivecatalysts,catalyst4waschosenforfurtherexamination.Havingoptimizedreactionconditions,thesubstratescopeofthereactionwasexplored(Table3).Itwasfoundthatelectronrichcomparedtoelectronpooraromaticaldehydesprovedtobemorereactiveandselective(entries6,7,9,10).Aliphaticaldehydescouldalsobeused,furtherestablishingtheutilityofoursystem(entries11,12).Allreactionsproceededveryquickly,withhighyieldsandenantioselectivity.Furthermore,thecatalystloadingcouldbedecreasedto0.5mol%withessentiallynolossinenantioselectivityoryieldwithslightlyprolongedreactiontimes(entries1,3,7).Uponfurtherinvestigationofthisligandsystemwithprevi-ouslysynthesizedligandsbyourgroup,itwasfoundthatthesubstitutionatthe5,5′-positionofthequinolineringhadadramaticincreaseontherateofthereaction.TodemonstrateScheme1.Synthesisof(R)-TBOxAlCl

※专题论述目晶科孛２０１４，Ｖ０１．３５，Ｎｏ．０９３１７

ＤＰＰＨ法评价抗氧化活性研究进展

韦献雅１，殷丽琴１，钟成２，章明海１，牛应泽“水（１．四川农业大学油菜研究中心，四川成都６１１１３０：２．四川农业大学玉米研究所，四川成都６１１１３０）

摘要：植物化合物或植物提取物的抗氧化活性的体外评价是研究功能因子的一个重要方面。１，１．二苯基．２．三硝基苯肼（１－ｄｉｐｈｅｎｙｌ一２．ｐｉｃｒｙｔｈｙｄｒａｚｙｌ，ＤＰＰＨ）法常用于评价化合物或植物提取物的抗氧化活性，但由于没有一个标准化的方法，因而不同实验的结果难于相互比较。本文从ＤＰＰＨ法的原理、测定方法、检测波长、ＤＰＰＨ初浓度、反应时间、清除率计算公式、结果表达、评价指标等几个方面对ＤＰＰＨ法做归纳总结，分析几种外界因素对ＤＰＰＨ法的影响，有助于研究者提高认识，从而准确的开展研究工作。关键词：ＤＨ＇Ｈ法；自由基；抗氧化剂；抗氧化活性

ＡｄｖａｎｃｅｓｉｎｔｈｅＤＰＰＨＲａｄｉｃａｌＳｃａｖｅｎｇｉｎｇＡｓｓａｙｆｏｒＡｎｔｉｏｘｉｄａｎｔＡｃｔｉｖｉｔｙＥｖａｌｕａｔｉｏｎ

ＷＥＩＸｉａｎ—ｙａｌ，ＹＩＮＬｉ－ｑｉｎｌ，ＺＨＯＮＧＣｈｅｎ９２，ＺＨＡＮＧＭｉｎｇ．ｈａｉｌ，ＮＩＵＹｉｎｇ—Ｚｅｌ－聋（１．ＲａｐｅｓｅｅｄＲｅｓｅａｒｃｈＣｅｎｔｅｒ，ＳｉｃｈｕａｎＡｇｒｉｃｕｌｔｕｒａｌＵｎｉｖｅｒｓｉｔｙ，Ｃｈｅｎｇｄｕ６１１１３０，Ｃｈｉｎａ；２．ＭａｉｚｅＲｅｓｅａｒｃｈＩｎｓｔｉｔｕｔｅ，ＳｉｃｈｕａｎＡｇｒｉｃｕｌｔｕｒａｌＵｎｉｖｅｒｓｉｔｙ，Ｃｈｅｎｇｄｕ６１１１３０，Ｃｈｉｎａ）

Ａｂｓｔｒａｃｔ：／ｎｖｉｔｒｏｅｖａｌｕａｔｉｏｎｏｆｔｈｅａｎｔｉｏｘｉｄａｎｔａｃｔｉｖｉｔｙｏｆｐｌａｎｔｃｏｍｐｏｕｎｄｓｏｒ＃ａｎｔｅｘｔｒａｃｔｓｉｓａｌｌｉｍｐｏｒｔａｎｔａｓｐｅｃｔｏｆｆｕｎｃｔｉｏｎａｌｆａｃｔｏｒｒｅｓｅａｒｃｈ．ｒｎｌｅＤＰＰＨ（１－ｄｉｐｈｅｎｙｌ·２－ｐｉｃｒｙｌｈｙｄｒａｚｙｌ）ｒａｄｉｃａｌｓｃａｖｅｎｇｉｎｇａｓｓａｙｉｓｗｉｄｅｌｙｕｓｅｄｆｏｒａｎｔｉｏｘｉｄａｎｔａｃｔｉｖｉｔｙｅｖａｌｕａｔｉｏｎｏｆｐｌａｎｔｃｏｍｐｏｕｎｄｓａｎｄｅｘｔｒａｃｔｓ．Ｈｏｗｅｖｅｒ，ｔｈｉｓｍｅｔｈｏｄｌａｃｋｓａｓｔａｎｄａｒｄｉｚｅｄｐｒｏｇｒａｍＳＯｔｈａｔｒｅｓｕｌｔｓｆｒｏｍｄｉｆｆｅｒｅｎｔｅｘｐｅｒｉｍｅｎｔｓｍａｙｂｅｄｉｆｆｉｃｕｌｔｔｏｃｏｍｐａｒｅｗｉｔｌｌｅａｃｈｏｔｈｅｒ．Ｔｈｅｐｒｅｓｅｎｔｒｅｖｉｅｗｐｒｅｓｅｎｔｓａｃｏｍｐｒｅｈｅｎｓｉｖｅｏｖｅｒｖｉｅｗｏｆｔｈｅｐｒｉｎｃｉｐｌｅ，ｍｅａｓｕｒｅｍｅｎｔｐｒｏｃｅｄｕｒｅａｎｄｗａｖｅｌｅｎｇｔｈ，ｉｎｉｔｉａｌＤＰＰＨｆｒｅｅｒａｄｉｃａｌｃｏｎｃｅｎｔｒａｔｉｏｎ，ｒｅａｃｔｉｏｎｔｉｍｅ，ｃａｌｃｕｌａｔｉｏｎｏｆｔｈｅｓｃａｖｅｎｇｉｎｇｒａｔｅ，ｅｘｐｒｅｓｓｉｏｎｏｆｒｅｓｕｌｔｓａｎｄｅｖａｌｕａｔｉｏｎｉｎｄｉｃｅｓ．ＳｅｖｅｒａｌｅｘｔｅｒｎａｌｆａｃｔｏｒｓｉｎｆｌｕｅｎｃｉｎｇｔｈｅＤＰＰＨａｓｓａｙａｌｅａｌｓｏｄｉｓｃｕｓｓｅｄ．Ｋｅｙｗｏｒｄｓ：ＤＰＰＨｍｅｔｌｌｏｄ；ｆｒｅｅｒａｄｉｃａｌ；ａｎｔｉｏｘｉｄａｎｔ；ａｎｔｉｏｘｉｄａｎｔａｃｔｉｖｉｔｙ中图分类号：ＴＳ２０７．３文献标志码：Ａ文章编号：１００２—６６３０（２０１４）０９．０３１７－０６