郑州大学 有机化学4立体化学

ItisFebruary,1929.InalonelycottageinDevonshire,G.Harrison,amiddle-agedamateurmycologist(真菌学爱好者),hasdiedshortlyaftereatingamushroomstew(炖菜)hepreparedfromwartycaps(疣帽菇)collectedinnearbyFive-AcreWood.Causeofdeath:poisoningbymuscarine(蕈毒碱),analkaloid(生物碱)foundintheflyagaric(蝇伞菌).Didadeadlyflyagaricfinditswayaccidentallyintothemessofsimilar,butharmlesswartycaps?Wasalethaldoseofsyntheticmuscarine(filchedfromaLondonlaboratory),deliberatelyandwithmaliceaforethought(预谋),addedtothestewpot——perhapsbytheloverofbeautifulMrs.Harrison?——KeithManchester.

BiochemistryandMolecularBiologyEducation,2007,35(3),169-171.Chapter4StereochemistryIsomerism(同分异构)constitutional~(构造异构)stereoisomerism(立体异构)configurational~(构型异构)conformational~(构象异构)cis-andtrans-~(顺反异构)enantiomerism(对映异构)In1886,achemistisolatedfromspoutingvetchawhitesubstancewiththesamemolecularformulaandstructure,butithasasweettaste.Asparagineisawhitesolidthatwasfirstisolatedin1806fromthejuiceofasparagus.Whenitisfromthissource,asparagineshasabittertaste.ItsmolecularformulaisC4H8N2O3.EnantiomersThebitter-sweetstoryofasparagines(天冬酰胺)Tasteisachemicalsense,sothetwosamplesofasparaginesdohaveonedifferenceinchemicalproperty.1.Opticalactivity(旋光性，光学活性)Apolarimeter(旋光仪)Thesampleisopticallyactiveifitrotatestheplaneofpolarizedlight.(+)-lacticacid(-)-lacticacid

(±)-lacticacidracemiclacticacid右旋乳酸

左旋乳酸

外消旋乳酸Apairofenantiomers(一对对映体)Clockwisedirection(顺时针):dextrorotatory(右旋)or(+)Counter-clockwise(逆时针):levorotatory(左旋)or(-)2.Specificrotation(比旋光度)α:

observedrotationl:

samplepathlength(dm)c:

sampleconcentration(g/mL)(+)-Muscarine(蕈毒碱),adeadlyalkaloid(生物碱)foundintheflyagaric(蝇伞菌)HistoricalOriginofEnantiomerism

LouisPasteur(巴斯德)in1848noticedthesodiumammonium

salt

(钠氨盐)ofopticallyinactivetartaricacid

(酒石酸)

wasamixtureoftwomirror-imagecrystalforms.LouisPasteur’sdiscoveryofenantiomerism(对映异构)led,in1874,totheproposalof

thetetrahedralstructureofcarbonbyvan’tHoff(范特霍夫)(1852-1911)

and

Le

Bel

(1847-1930).HermannKolbe

(1818-1884)criticizedstronglyvan’tHoff’spublicationon“The

ArrangementsofAtomsinSpace”.Hewrote,“Thispaperisfancifulnonsense…likeafashionablydressedandpaintedprostitute”3.Chiralityofmolecules(分子的手性)Themirrorimage(镜像)ofa

left

hand

isa

righthand.

Left

andrighthandsarenot

superimposable(重合).3.1Chirality(手性)=“-handedness”In1894,WilliamThomson(LordKelvin)coinedawordforthisproperty.Hedefinedanobjectaschiralifitisnotsuperimposableonitsmirrorimage.Tobeopticallyactive,thesamplemustcontainachiralsubstanceandoneenantiomermustbepresentinexcessoftheother.Allachiral(非手性)substancesareopticallyinactive.Chiralorachiral?TheancientEgyptianshadlesscareforthechiralityofhandsandtheirpaintingsoftenshowpeople,evenPharaohs,withtwolefthandsortworighthands—theyjustdidn’tseemtonotice.Apairofenantiomers:Oneis(+)-andtheotheris(-)-.3.2Symmetricfactors(对称因素)3.2.1Symmetricplane(对称面)3.2.2Symmetriccenter(对称中心)Anymoleculewithaplaneofsymmetryoracenterofsymmetryisachiral.Amoleculelackingacenterofsymmetryandaplaneofsymmetryislikelytobechiral.3.3Chiralcarbon(手性碳)Atetrahedralcarbonatomthatbearsfourdifferent

atomsorgroupsiscalledachiral

carbon

(*C).***********************Oleandrin(夹竹桃甙)isatoxiccardiacglycoside(强心甙)foundinOleander(夹竹桃).4.Moleculeswithonlyonechiralcarbon(仅含一个手性碳的分子)Anymoleculewithonlyonechiralcarbonischiral.*4.1Representationsofmoleculescontainingchiralcarbons:Fischerprojection(含手性碳分子的表示方法:Fischer投影式)FischerprojectionTheFischerprojection,devisedbyH.E.Fischerin1891,isatwo-dimensionalrepresentationofathree-dimensionalorganicmoleculebyprojection.Convention(规定):Thecarbonchainisdrawnalongthevertical

lineofthe

Fischerprojection,usuallywiththemosthighlyoxidized

endcarbonatomatthetop.1)Verticallines

(竖线):bondsgoingintothepage.2)Horizontallines

(横线):bondscomingoutofthepage.横前竖后！Aretheythesamemolecules?AllowedmotionsforFischerprojection:1)

180°

rotation(not90°or270°):=2)90°rotation:RotationofaFischerprojectionby90°invertsitsmeaning.≠3)Onegroupholdsteadyandtheotherthreecanrotate:=(1)=(3)=(4)≠(2)Exchangingthepositionsofanytwogroups

eventimes(偶数次)willnotchangeitsconfiguration.(1)=(3)=(4)≠(2)4.2Nomenclatureofenantiomers:relativeandabsoluteconfigurations(对映异构体的命名:相对构型与绝对构型)4.2.1Relative

configurations:theD-/L-system(相对构型:D-/L-体系)Glyceraldehyde(甘油醛)

D-(+)-glyceraldehydeL-(-)-glyceraldehydeGlyceraldehydeisoneofthesimplestchiralcompoundsinnature.Becauseofthis,chemiststookitasastandardagainstwhichtheconfigurationsofothercompoundscouldbecompared.ThetwoenantiomersofglyceraldehydeweregiventhelabelsD(fordextro(右旋)-becauseitwasthe(+)-enantiomer)andL(forlaevo(左旋)-becauseitwasthe(–)-enantiomer).Anyenantiomericallypurecompoundthatcouldberelated,byaseriesofchemicaldegradationsandtransformations,toD-(+)-glyceraldehydewaslabelledD,andanycompoundthatcouldberelatedtoL-(–)-glyceraldehydewaslabelledL.D-(-)-lacticacid(乳酸)L-(+)-lacticacidInpractice,sugarchemistry,aminoacidchemistryandnaturalproductchemistryareconstructedontheD-/L-system.(1)Allbutoneofthe20aminoacidsthatmakeupnaturally

occurring

proteinsare

chiral,andallofthemareclassifiedas

beingleft

handed(L).(2)Themoleculesofnaturalsugarsarealmostallclassifiedas

being

righthanded(D),includingthesugarthat

occursin

DNA.(3)DNAhasahelicalstructure,andallnaturallyoccurringDNA

turns

totheright.ThecorrelationbetweenD-(–)-lacticacidandD-(+)-glyceraldehydeR.S.Cahn,C.K.Ingold,andV.PrelogdevisedtheR-/S-system

(sequencerule)

fordesignatingtheconfigurationofchiralcarbonatoms.

-H（氢）<-D（氘）<-CH3（甲基）<-CH2CH3（乙基）<-CH2CH2CH3（丙基）<-CH2C6H5（苯甲基、苄基）<-CH(CH3)2（异丙基）<-CH=CH2（乙烯基）<-C(CH3)3（叔丁基）<-C6H5（苯基）<-C≡CH（乙炔基）<-CH2NH2（氨甲基）

<-C≡N（氰基）<-CH2OH（羟甲基）<-CHO（醛基、甲酰基）<-COCH3（乙酰基）<-COOH（羧基）<-COOCH3（甲氧羰基、甲酯基）<-NH2（氨基）<-NHCHO（甲酰氨基）<-NHCOCH3（乙酰氨基）<-N(CH3)2（二甲氨基）<-N+≡N（重氮基）<-NO（亚硝基）<-NO2（硝基）<-OH（羟基）<-OCH3（甲氧基）<-OCOH（甲酰氧基）<-OCOCH3（乙酰氧基）<-F（氟）<-SH（巯基）<-SO3H（磺酸基）<-Cl（氯）<-Br（溴）<-I（碘）

4.2.2Absolute

configurations:theR-/S-system(绝对构型:R-/S-体系)1)Thepriority(优先次序)offourgroupsisdecidedbythesequencerule:L>M>S>s.LsSM2)Wesupposelookingalongthebondfromthechiralcarbontowardthegroupofthelowestpriority(s).Theotherthreegroups(L,MandS)willfaceus.3)Connectthesethreegroupswithanarrowrunningfromhighesttolowestpriority(L>M>S).4)Ifthisarrowrunsclockwise(顺时针),theenantiomeriscalledR.Ifitrunscounterclockwise(逆时针),theenantiomeriscalledS.(R)-lacticacid(S)-lacticacidLevonorgestrel

(左炔诺孕酮)Levonorgestrelisasyntheticprogestogen(孕激素)usedasanactivehormonalingredientinemergencycontraceptivepills.Therearemanybrandnamesoflevonorgestrel,includingEscapelle,PlanB,i-pill,NextChoiceand72-HOURS.*SHowmanychiralcarbons?Determinetheabsoluteconfigurationofthelabeledcarbon.Practice1.AssigntheabsoluteconfigurationsasRorStoeachchiralcarbonofthefollowingcompounds:2.Namethefollowingcompounds:(S,E)-3-戊烯-2-醇(S)-4-甲基-3-苯基-3-氨基-1-戊烯3.Tamiflu(达菲),anantiviraldrugthatisusedinthetreatmentofinfluenzaA(H1N1)

virusinfection,canbesynthesizedfrom(-)-shikimicacid(莽草酸),whichisfoundinChinesestaranise.AssignabsoluteconfigurationsasRorStoeachchiralcarbonintamifluand(-)-shikimicacid,andwritetheconfigurationalformulaof(+)-shikimicacid.(-)-ShikimicacidTamiflu4.Cicutoxin(毒芹素),whoseIUPACnameis(R,8E,10E,12E)-8,10,12-heptadeca-trien-4,6-diyne-1,14-diol,isapoisonouspolyyneandalcoholfoundinvariousplants,mostnotablywaterhemlock

(水毒芹).Writetheconstitutionalformulaofcicutoxin,andgivethenumberoftheopticalisomers.Nowcanyouwritealltheconfigurationalformulasandnamethem?16opticalisomers!≡(R)-HowtodeterminetheabsoluteconfigurationforFischerprojectionPractice(R)-(R)-sverticalnormal(小在竖，正标定)shorizontalinverse(小在横，反标定)(R)-(R)-(S)-:1=2=3=4=6(R)-:5PracticeAretheythesamemolecules?Exchangingthepositionsofanytwogroupseventimeswillnotchangeitsconfiguration

(任意两个基团对调偶数次，构型不变).(R)-:1=3=4(S)-:2Whichmoleculesaretheenantiomersof(S)-2-methylbutanoicacid

？Practice4.3Propertiesofenantiomersandracemates(对映异构体和外消旋体的性质)PhysicalpropertiesChemicalreactions(+)-glucose(葡萄糖):canbemetabolized(-)-adrenaline(肾上腺素):moreactive(-)-nicotine(尼古丁):moretoxic(+)-carvone(香芹酮):spearmint(薄荷)oil(-)-carvone:caraway(香菜)seedoilRacemates(外消旋体):seperation(distillation,fractionaldistillation,recrystallization,chromatography×)Resolution(拆分)Biologicalactivities“monsterdrug(怪物药)”“wonderdrug(灵丹妙药)”Thalidomide(反应停)(R)-Thalidomide中枢镇静作用(S)-Thalidomide致畸性(S)-Penicillamine:highlypotenttherapeuticagentforprimarychronicarthritis(关节炎).The(R)-enantiomerhasnotherapeuticactionanditishighlytoxic.(多巴)(青酶胺)(天门冬酰胺)4.4Someconcepts

(几个概念)EnantiomericExcess(对映体过量)

(ee)WhereM+

is

themolefractionofthedextrorotatoryenantiomer,

andM-

themolefractionofthelevorotatoryone.Opticalpurity(光学纯度)(op)已知2-甲基-1-氯丁烷的[α]=+1.64°，现有一个不对称合成该化合物的样品，经测定其比旋光度为+0.82°，求该样品的光学纯度百分率和(+)、(-)对映体的组成比。右旋体∶左旋体=75∶25Prochiralcarbon(潜手性碳)Iftwoidenticalsubstituentsareattachedtoasp3-hybridizedatom,thedescriptorspro-Randpro-Sareusedtodistinguishbetweenthetwo.Promotingthepro-RsubstituenttohigherprioritythantheotheridenticalsubstituentresultsinanRchiralitycenterattheoriginalsp3-hybridizedatom,andanalogouslyforthepro-Ssubstituent.Ifasymmetriccarboncanbesubstitutedandbecomesasymmetricinasinglestep,itiscalleda‘prochiralcarbon’.Atrigonalplanarsp2-hybridizedatomcanbeconvertedtoachiralcenterwhenasubstituentisaddedtothereorsifaceofthemolecule.Afaceislabeledreif,whenlookingatthatface,thesubstituentsatthetrigonalatomarearrangedindecreasingCahn-Ingold-Prelogpriorityorderinaclockwiseorder,andsiiftheprioritiesdecreaseincounter-clockwiseorder.re/siface5.Moleculeswithtwodifferentchiralcarbons(含两个不同手性碳的分子)ⅣⅠⅡⅢ(2S,3S)-~(2R,3R)-~(2R,3S)-~(2S,3R)-~Diastereomers(非对映体)赤式苏式apairofenantiomer(对映体)apairofenantiomerWhenthecarbonchainisverticalandlikesubstituentsareonthesamesideoftheFischerprojection,themoleculeisdescribedastheerythrodiastereomer(赤式).WhenlikesubstituentsareonoppositesidesoftheFischerprojection,themoleculeisdescribedasthethreodiastereomer(苏式).

Threo-anderythro-(赤式和苏式)(i)(ii)(iii)(iv)(2R,3R)-(-)-赤藓糖(2S,3S)-(+)-赤藓糖(2S,3R)-(+)-苏阿糖(2R,3S)-(-)-苏阿糖Practice(2S,3S)-2,3-二溴戊烷(2R,3R)-3-氯-2-丁醇(2S,3R)-2-氯-3-溴丁烷Namesthefollowingmolecues.Aretheythreo-orerythro-?(2S,3S)-3-羟基-2-氯丁酸赤式(2R,3S)-3-甲基-2-氯戊醛苏式FischerprojectionNewmanprojectionconfiguration1.Givethename,andconverttheFischerprojectionintotheNewmanprojectionandthewedge-and-dashformula.Isitthreo-orerythro-diastereomer?(2S,3R)-2-氯-3-碘丁烷2.GivethenamesandtheFischerprojections.Aretheythreo-orerythro-diastereomer?(2R,3R)-3-羟基-2-氯丁醛(2R,3R)-(2R,3R)-6.Moleculeswithtwosamechiralcarbons(含两个相同手性碳的分子)Tartaricacid(酒石酸)(+)-酒石酸(-)-酒石酸(R)(R)(S)(S)(R)(S)meso-酒石酸Mesomer(内消旋体)

(2R,3S)-酒石酸(S)(R)从构象的角度来看酒石酸的立体异构对映体重叠式交叉式重叠式交叉式内消旋体1.WhatistheIUPACnameof(+)-pseudoephedrine(右旋伪麻黄碱)?WhichFischerprojectionisright?2.Whataretherelationshipsamongthefollowingmolecules?A与B非对映体A与C对映体A与D非对映体B与C非对映体RRRRSSSSB与D相同！(1S,2S)-2-(methylamino)-1-phenyl-1-propanolN-methyl-1-phenylpropan-2-amineIce(drug),nicknameforMethamphetamine止咳治疗哮喘治疗心脑血管疾病治疗癫痫阿拉伯糖来苏糖木糖核糖7.Moleculeswiththreechiralcarbons(含三个手性碳的分子)Themaximumnumberofstereoisomersforaparticularconstitutionis2n.Epimers(差向异构):Twostereoisomersthathavemultiplechiralcentersbutdifferinconfigurationatonlyoneofthemarereferredtoasepimers.

Anomers

(端基异构)(2R,4R)-(2R,3s,4S)-假不对称碳的构型用r/s表示。在顺序规则中，R优先于S，顺优先于反(Z优先于E)。pseudochiralcarbon,pseudoasymmetriccarbon(假手性碳原子,伪不对称碳)Apseudochiralcarbonisacarbonthathasfourdifferentsubstituents,andtheonlydifferencebetweentwosubstituents

istheirchirality(一个碳原子与四个不同取代基相连，且其中两个取代基相同，但手性构型不同，该碳原子称为假手性碳)。2,3,4-三羟基戊二酸RrsRRSSRSSOnly4stereoisomers!ApairofenantiomersTwomesomers(4r,2Z,5E)-4-氯-2,5-庚二烯7123456(2Z,4E)-2,4-己二烯6123458.Moleculeswithoutchiralcarbons(不含手性碳的分子)8.1Chiralcenterotherthancarbon

(其它手性中心)8.2Allenes(丙二烯类)手性轴sp杂化8.3Biphenyls(联苯类)

在联苯型分子中，当两个苯环的邻位上都连有体积较大的基团时，基团将阻碍两个苯环绕碳碳单键的自由旋转，使得两个苯环不能在同一平面上。构象异构体，但室温下不能相互转化无对映异构体手性轴Atropisomer(位阻异构体)8.4Helicenes(螺烃类)Coronene(蒄)六螺苯手性面顺-1,2-二溴环丙烷反-1,2-二溴环丙烷(1R,2S)-1,2-二溴环丙烷9.Stereoisomerismofcycliccompounds

(环状化合物的立体异构)

(1R,2R)-1,2-环丙烷二甲酸Namethefollowingcompounds?Aretheyopticallyactive?(1R,2S)-1-甲基-2-乙基环丁烷SRRSSR(1S,2S)-RSSRSR(1R,2S)-1,4-Dimethylcyclohexanescis-andtrans-1,3-DimethylcyclohexanesRScis-1,3-二甲基环己烷(1R,3S)-RSRSRSRRSS1,2-Dimethylcyclohexanes顺-1,2-二甲基环己烷用平面构型式分析，尽管具有手性碳，但因为存在着对称面，分子无手性，化合物是内消旋体。用构象式分析，其两种典型构象不存在对称面以及对称中心，均具有手性，但可以相互转化。化合物是外消旋体。SRSRSRSRSSRRSR十氢萘顺式反式顺式和反式异构体从平面构型来看，因为存在着对称面，均无手性，化合物均无旋光性。顺式十氢萘的两种典型构象不存在对称面以及对称中心，均具有手性，但可以相互转化。故从构象来看，顺式十氢萘是外消旋体，无旋光性。反式十氢萘从构象来看，因为存在对称面以及对称中心，无手性，化合物无旋光性。顺式存在着可以相互转化的构象异构体，而反式则不存在1.Quinine(奎宁),obtainedfromthebarkofthecinchonatree(金