鄭州大學(xué) 有機(jī)化學(xué)4立體化學(xué)

ItisFebruary,1929.InalonelycottageinDevonshire,G.Harrison,amiddle-agedamateurmycologist(真菌學(xué)愛好者),hasdiedshortlyaftereatingamushroomstew(燉菜)hepreparedfromwartycaps(疣帽菇)collectedinnearbyFive-AcreWood.Causeofdeath:poisoningbymuscarine(蕈毒堿),analkaloid(生物堿)foundintheflyagaric(蠅傘菌).Didadeadlyflyagaricfinditswayaccidentallyintothemessofsimilar,butharmlesswartycaps?Wasalethaldoseofsyntheticmuscarine(filchedfromaLondonlaboratory),deliberatelyandwithmaliceaforethought(預(yù)謀),addedtothestewpot——perhapsbytheloverofbeautifulMrs.Harrison?——KeithManchester.

BiochemistryandMolecularBiologyEducation,2007,35(3),169-171.Chapter4StereochemistryIsomerism(同分異構(gòu))constitutional~(構(gòu)造異構(gòu))stereoisomerism(立體異構(gòu))configurational~(構(gòu)型異構(gòu))conformational~(構(gòu)象異構(gòu))cis-andtrans-~(順反異構(gòu))enantiomerism(對映異構(gòu))In1886,achemistisolatedfromspoutingvetchawhitesubstancewiththesamemolecularformulaandstructure,butithasasweettaste.Asparagineisawhitesolidthatwasfirstisolatedin1806fromthejuiceofasparagus.Whenitisfromthissource,asparagineshasabittertaste.ItsmolecularformulaisC4H8N2O3.EnantiomersThebitter-sweetstoryofasparagines(天冬酰胺)Tasteisachemicalsense,sothetwosamplesofasparaginesdohaveonedifferenceinchemicalproperty.1.Opticalactivity(旋光性，光學(xué)活性)Apolarimeter(旋光儀)Thesampleisopticallyactiveifitrotatestheplaneofpolarizedlight.(+)-lacticacid(-)-lacticacid

(±)-lacticacidracemiclacticacid右旋乳酸

左旋乳酸

外消旋乳酸Apairofenantiomers(一對對映體)Clockwisedirection(順時(shí)針):dextrorotatory(右旋)or(+)Counter-clockwise(逆時(shí)針):levorotatory(左旋)or(-)2.Specificrotation(比旋光度)α:

observedrotationl:

samplepathlength(dm)c:

sampleconcentration(g/mL)(+)-Muscarine(蕈毒堿),adeadlyalkaloid(生物堿)foundintheflyagaric(蠅傘菌)HistoricalOriginofEnantiomerism

LouisPasteur(巴斯德)in1848noticedthesodiumammonium

salt

(鈉氨鹽)ofopticallyinactivetartaricacid

(酒石酸)

wasamixtureoftwomirror-imagecrystalforms.LouisPasteur’sdiscoveryofenantiomerism(對映異構(gòu))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(鏡像)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(對稱因素)3.2.1Symmetricplane(對稱面)3.2.2Symmetriccenter(對稱中心)Anymoleculewithaplaneofsymmetryoracenterofsymmetryisachiral.Amoleculelackingacenterofsymmetryandaplaneofsymmetryislikelytobechiral.3.3Chiralcarbon(手性碳)Atetrahedralcarbonatomthatbearsfourdifferent

atomsorgroupsiscalledachiral

carbon

(*C).***********************Oleandrin(夾竹桃甙)isatoxiccardiacglycoside(強(qiáng)心甙)foundinOleander(夾竹桃).4.Moleculeswithonlyonechiralcarbon(僅含一個(gè)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(規(guī)定):Thecarbonchainisdrawnalongthevertical

lineofthe

Fischerprojection,usuallywiththemosthighlyoxidized

endcarbonatomatthetop.1)Verticallines

(豎線):bondsgoingintothepage.2)Horizontallines

(橫線):bondscomingoutofthepage.橫前豎后！Aretheythesamemolecules?AllowedmotionsforFischerprojection:1)

180°

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

eventimes(偶數(shù)次)willnotchangeitsconfiguration.(1)=(3)=(4)≠(2)4.2Nomenclatureofenantiomers:relativeandabsoluteconfigurations(對映異構(gòu)體的命名:相對構(gòu)型與絕對構(gòu)型)4.2.1Relative

configurations:theD-/L-system(相對構(gòu)型:D-/L-體系)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（氫）<-D（氘）<-CH3（甲基）<-CH2CH3（乙基）<-CH2CH2CH3（丙基）<-CH2C6H5（苯甲基、芐基）<-CH(CH3)2（異丙基）<-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（羥甲基）<-CHO（醛基、甲?；?lt;-COCH3（乙?；?lt;-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（亞硝基）<-NO2（硝基）<-OH（羥基）<-OCH3（甲氧基）<-OCOH（甲酰氧基）<-OCOCH3（乙酰氧基）<-F（氟）<-SH（巰基）<-SO3H（磺酸基）<-Cl（氯）<-Br（溴）<-I（碘）

4.2.2Absolute

configurations:theR-/S-system(絕對構(gòu)型:R-/S-體系)1)Thepriority(優(yōu)先次序)offourgroupsisdecidedbythesequencerule:L>M>S>s.LsSM2)Wesupposelookingalongthebondfromthechiralcarbontowardthegroupofthelowestpriority(s).Theotherthreegroups(L,MandS)willfaceus.3)Connectthesethreegroupswithanarrowrunningfromhighesttolowestpriority(L>M>S).4)Ifthisarrowrunsclockwise(順時(shí)針),theenantiomeriscalledR.Ifitrunscounterclockwise(逆時(shí)針),theenantiomeriscalledS.(R)-lacticacid(S)-lacticacidLevonorgestrel

(左炔諾孕酮)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(達(dá)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(小在豎，正標(biāo)定)shorizontalinverse(小在橫，反標(biāo)定)(R)-(R)-(S)-:1=2=3=4=6(R)-:5PracticeAretheythesamemolecules?Exchangingthepositionsofanytwogroupseventimeswillnotchangeitsconfiguration

(任意兩個(gè)基團(tuán)對調(diào)偶數(shù)次，構(gòu)型不變).(R)-:1=3=4(S)-:2Whichmoleculesaretheenantiomersof(S)-2-methylbutanoicacid

？Practice4.3Propertiesofenantiomersandracemates(對映異構(gòu)體和外消旋體的性質(zhì))PhysicalpropertiesChemicalreactions(+)-glucose(葡萄糖):canbemetabolized(-)-adrenaline(腎上腺素):moreactive(-)-nicotine(尼古丁):moretoxic(+)-carvone(香芹酮):spearmint(薄荷)oil(-)-carvone:caraway(香菜)seedoilRacemates(外消旋體):seperation(distillation,fractionaldistillation,recrystallization,chromatography×)Resolution(拆分)Biologicalactivities“monsterdrug(怪物藥)”“wonderdrug(靈丹妙藥)”Thalidomide(反應(yīng)停)(R)-Thalidomide中樞鎮(zhèn)靜作用(S)-Thalidomide致畸性(S)-Penicillamine:highlypotenttherapeuticagentforprimarychronicarthritis(關(guān)節(jié)炎).The(R)-enantiomerhasnotherapeuticactionanditishighlytoxic.(多巴)(青酶胺)(天門冬酰胺)4.4Someconcepts

(幾個(gè)概念)EnantiomericExcess(對映體過量)

(ee)WhereM+

is

themolefractionofthedextrorotatoryenantiomer,

andM-

themolefractionofthelevorotatoryone.Opticalpurity(光學(xué)純度)(op)已知2-甲基-1-氯丁烷的[α]=+1.64°，現(xiàn)有一個(gè)不對稱合成該化合物的樣品，經(jīng)測定其比旋光度為+0.82°，求該樣品的光學(xué)純度百分率和(+)、(-)對映體的組成比。右旋體∶左旋體=75∶25Prochiralcarbon(潛手性碳)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(含兩個(gè)不同手性碳的分子)ⅣⅠⅡⅢ(2S,3S)-~(2R,3R)-~(2R,3S)-~(2S,3R)-~Diastereomers(非對映體)赤式蘇式apairofenantiomer(對映體)apairofenantiomerWhenthecarbonchainisverticalandlikesubstituentsareonthesamesideoftheFischerprojection,themoleculeisdescribedastheerythrodiastereomer(赤式).WhenlikesubstituentsareonoppositesidesoftheFischerprojection,themoleculeisdescribedasthethreodiastereomer(蘇式).

Threo-anderythro-(赤式和蘇式)(i)(ii)(iii)(iv)(2R,3R)-(-)-赤蘚糖(2S,3S)-(+)-赤蘚糖(2S,3R)-(+)-蘇阿糖(2R,3S)-(-)-蘇阿糖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-羥基-2-氯丁酸赤式(2R,3S)-3-甲基-2-氯戊醛蘇式FischerprojectionNewmanprojectionconfiguration1.Givethename,andconverttheFischerprojectionintotheNewmanprojectionandthewedge-and-dashformula.Isitthreo-orerythro-diastereomer?(2S,3R)-2-氯-3-碘丁烷2.GivethenamesandtheFischerprojections.Aretheythreo-orerythro-diastereomer?(2R,3R)-3-羥基-2-氯丁醛(2R,3R)-(2R,3R)-6.Moleculeswithtwosamechiralcarbons(含兩個(gè)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(內(nèi)消旋體)

(2R,3S)-酒石酸(S)(R)從構(gòu)象的角度來看酒石酸的立體異構(gòu)對映體重疊式交叉式重疊式交叉式內(nèi)消旋體1.WhatistheIUPACnameof(+)-pseudoephedrine(右旋偽麻黃堿)?WhichFischerprojectionisright?2.Whataretherelationshipsamongthefollowingmolecules?A與B非對映體A與C對映體A與D非對映體B與C非對映體RRRRSSSSB與D相同！(1S,2S)-2-(methylamino)-1-phenyl-1-propanolN-methyl-1-phenylpropan-2-amineIce(drug),nicknameforMethamphetamine止咳治療哮喘治療心腦血管疾病治療癲癇阿拉伯糖來蘇糖木糖核糖7.Moleculeswiththreechiralcarbons(含三個(gè)手性碳的分子)Themaximumnumberofstereoisomersforaparticularconstitutionis2n.Epimers(差向異構(gòu)):Twostereoisomersthathavemultiplechiralcentersbutdifferinconfigurationatonlyoneofthemarereferredtoasepimers.

Anomers

(端基異構(gòu))(2R,4R)-(2R,3s,4S)-假不對稱碳的構(gòu)型用r/s表示。在順序規(guī)則中，R優(yōu)先于S，順優(yōu)先于反(Z優(yōu)先于E)。pseudochiralcarbon,pseudoasymmetriccarbon(假手性碳原子,偽不對稱碳)Apseudochiralcarbonisacarbonthathasfourdifferentsubstituents,andtheonlydifferencebetweentwosubstituents

istheirchirality(一個(gè)碳原子與四個(gè)不同取代基相連，且其中兩個(gè)取代基相同，但手性構(gòu)型不同，該碳原子稱為假手性碳)。2,3,4-三羥基戊二酸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(丙二烯類)手性軸sp雜化8.3Biphenyls(聯(lián)苯類)

在聯(lián)苯型分子中，當(dāng)兩個(gè)苯環(huán)的鄰位上都連有體積較大的基團(tuán)時(shí)，基團(tuán)將阻礙兩個(gè)苯環(huán)繞碳碳單鍵的自由旋轉(zhuǎn)，使得兩個(gè)苯環(huán)不能在同一平面上。構(gòu)象異構(gòu)體，但室溫下不能相互轉(zhuǎn)化無對映異構(gòu)體手性軸Atropisomer(位阻異構(gòu)體)8.4Helicenes(螺烴類)Coronene(蒄)六螺苯手性面順-1,2-二溴環(huán)丙烷反-1,2-二溴環(huán)丙烷(1R,2S)-1,2-二溴環(huán)丙烷9.Stereoisomerismofcycliccompounds

(環(huán)狀化合物的立體異構(gòu))

(1R,2R)-1,2-環(huán)丙烷二甲酸Namethefollowingcompounds?Aretheyopticallyactive?(1R,2S)-1-甲基-2-乙基環(huán)丁烷SRRSSR(1S,2S)-RSSRSR(1R,2S)-1,4-Dimethylcyclohexanescis-andtrans-1,3-DimethylcyclohexanesRScis-1,3-二甲基環(huán)己烷(1R,3S)-RSRSRSRRSS1,2-Dimethylcyclohexanes順-1,2-二甲基環(huán)己烷用平面構(gòu)型式分析，盡管具有手性碳，但因?yàn)榇嬖谥鴮ΨQ面，分子無手性，化合物是內(nèi)消旋體。用構(gòu)象式分析，其兩種典型構(gòu)象不存在對稱面以及對稱中心，均具有手性，但可以相互轉(zhuǎn)化?；衔锸峭庀w。SRSRSRSRSSRRSR十氫萘順式反式順式和反式異構(gòu)體從平面構(gòu)型來看，因?yàn)榇嬖谥鴮ΨQ面，均無手性，化合物均無旋光性。順式十氫萘的兩種典型構(gòu)象不存在對稱面以及對稱中心，均具有手性，但可以相互轉(zhuǎn)化。故從構(gòu)象來看，順式十氫萘是外消旋體，無旋光性。反式十氫萘從構(gòu)象來看，因?yàn)榇嬖趯ΨQ面以及對稱中心，無手性，化合物無旋光性。順式存在著可以相互轉(zhuǎn)化的構(gòu)象異構(gòu)體，而反式則不存在1.Quinine(奎寧),obtainedfromthebarkofthecinchonatree(金