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Stereochemistry-II
KNG-CHM-102-Lecture4
+
Crystalliza*on
Chromatography
Enzyma*c
AssignmentofRandSconfiguraOons
Eachgroupassignedapriorityorpreferencea,b,c,ord.
FirstPrioritybasedontheatomicnumberoftheatom
directlyaIachedtothechiralitycenter.
lowestatomicnumber-lowestpriority,d;
thegroupwithnexthigheratomicnumberisgiventhe
nexthigherpriority,c;
Whenaprioritycannotbeassignedonthebasisofthe
atomicnumber,thenextsetofatomsinthe
unassignedgroupsisexamined.
ConOnuetheprocessOlladecisioncanbemade.
Assignapriorityatthefirstpointofdifference
Rotatetheformula(ormodel)sothatthe
groupwithlowestpriority(d)isdirected
awayfromyou
Traceapathfromatobtoc.
thedirecOonisclockwise,theenanOomerisdesignated(R).
thedirecOoniscounterclockwise,theenanOomeris(S).
AssigningEor
Zforolefins
Electronpairsareassignedthelowestpriority
ImportanceofChirality
ChiralDrugs
Advil,Motrin,Nuprin
•  (S)enanOomeristheacOveagent.
•  (R)isomerofibuprofenhasnoanOinflammatoryacOonandisslowly
convertedtothe(S)isomerinthebody
Aldomet
(S)Isomer
anOhypertensive
StereoselecOveSyntheses
ReacOonproducespreferenOallyoneenanOomeroveritsmirror
image,thereacOonissaidtobeenan*oselec*ve
ReacOonleadspreferenOallytoonediastereomeroverothers
thatarepossible,thereacOonissaidtobediastereoselec*ve
ReacOontobeeitherenanOoselecOveordiastereoselecOve,
achiralreagent,catalyst,orsolventmustassertaninfluence
onthecourseofthereacOon
-chiralinduc;on
Synthesisof2-butanolbythenickel-catalyzed
hydrogenaOonofbutanone
Twofacesofthetrigonalplanar
carbonylgroupinteractwiththe
metalsurfacewithequalprobability
NochiralinfluenceinthereacOon
pathway
Productobtainedasaracemic
mixtureofthetwoenanOomers:
(R)-()-2-butanoland(S)-()-2butanol.
Chemical
EnzymaOc
Atropisomerism
Sixfusedbenzeneringscannot
beplanarandgiverisetorighthandedandle]handed
enanOomers.
Spirocompounds
Planesofthebondsofallenesareperpendiculartoeachother
Chiralityduetobarriertoinversion
Lowenergybarrier
BecausethereisarelaOvelyhighenergybarriertoinversionof
thesetetrahedralmolecules,theycanbeobtainedaspure
enanOomers
Prochirality
Prochiralcarbon-willbecomeachirality
center(anasymmetriccarbon)ifoneof
thehydrogensisreplacedbyadeuterium
(oranygroupotherthanorOH).
Enzymesthatoxidizeethanol,calledalcoholdehydrogenases,
selecOvelyremovethepro-Rhydrogen
reductasesselecOvelyreduceacetaldehydefromthereface
Enan;oselec;vehydrogena;oncatalysts
Chiralligandsinorganometalliccompoundsthatserveascatalysts
forhydrogenaOonsandotherreacOons
Significanceofchiralligands:
industrialsynthesiseachyear
ofapproximately3500tonsof
(-)-mentholusingan
isomerizaOonreacOon
involvingarhodium(S)-BINAP
catalyst
1,2-Dimethylcyclohexane
twochiralcenters,fourstereoisomers,wecanisolateonlythreestereoisomers
trans-1,2-Dimethylcyclohexanehasno
planeofsymmetryandexistsasapairof
enanOomers
1,3-Dimethylcyclohexane
.
1,4-Dimethylcyclohexane
Thecisandtransformsof1,4-dimethylcyclohexanearediastereomersofeachother.
Bothcompoundsareachiral,
Chiralityinbiology
PREFERREDHANDEDNESSisacommontraitoflivingthings.
Snails,suchasLiguus
virgineus,aregenerally
right-handed,but
withinaspecies,le]handedhanded
versionsappearowing
tomutaOons
Bindweed,suchas
Convolvulusarvensis,
windstotherightlike
themajorityofhelical
plants.
Trumpethoneysuckle,
Lonicerasempervirens,
windstothele];
ThebacteriumBacillus
sub;lisnormallyforms
right-handedspiral
colonies;whenheated,
thesechangetole]handed.
Coloredboxesindicate
thepredominant
handedness.
Life’sMolecularHandedness
ChemicalreacOonsproduce
anequalmixtureofboth
mirror-imageforms
Alanineenan*omers
AminoacidsandothermoleculescentraltolifewerepresentbeforeselfreplicaOngorganismscameintobeing,
Theywerepresentinequalmirror-imageformsintheprimordialsoup.
1970:Murchisonmeteorite
-aminoacidsandothercomplexmoleculesassociatedwithlifewerepresent
-7–9%excessoffourL-aminoacidspresent
-  ElectromagneOcradiaOonemiIedinacorkscrewfashionfromthepolesof
spinningneutronstarscouldleadtoabiasofonemirror-imageisomerover
anotherwhenmoleculesformininterstellarspace.
Mirror-imageformsofthesemoleculesactuallypresentinunequalamounts
beforelifebegan,leadtosomesortofpreferenceaslifeevolved?
Biomolecularhandedness
D-Sugarsin
carbohydrates
L-Aminoacidsin
Proteins
Starchisle]
handedhelix
Helicesare
righthanded
D-Sugarsin
nucleicacids
A-/B-DNAareright
handed
Z-DNAisle]handed
Enzyme–AcOvesite
Chiralselec*on:Onlyoneofthe
twoaminoacidenanOomers
shown(thele]-handone)can
achievethree-pointbindingwith
thehypotheOcalbindingsite
(e.g.,inanenzyme).
ConfiguraOonalstandardsforallmonosaccharides
PriortoanyknownabsoluteconfiguraOons,theconfiguraOons
ofchiralmoleculeswererelatedtoeachotherthrough
reac;onsofknownstereochemistry
(R)-glyceraldehydeiscalledD-glyceraldehyde
(S)-glyceraldehydeiscalledL-glyceraldehyde.
Nomenclatureisusedwithaspecializedmeaninginthe
nomenclatureofcarbohydrates.
OneglyceraldehydeenanOomerisdextrorotatory(+)andthe
other,ofcourse,islevorotatory(-).
(R)-(+)-glyceraldehyde
ConfiguraOonalstandardsforall
monosaccharides
D-(+)-glyceraldehyde
(S)-(-)-glyceraldehyde
L-(-)-glyceraldehyde
Amonosaccharidewhosehighestnumberedchiralitycenter(thepenulOmate
carbon)hasthesameconfiguraOonasD-(+)-glyceraldehydeisdesignatedasaD
sugar;
-onewhosehighestnumberedchiralitycenterhasthesameconfiguraOon
asL-glyceraldehydeisdesignatedasanLsugar
DandLnomenclaturedesignaOonsarelike(R)and(S)designaOons
-notnecessarilyrelatedtotheopOcalrotaOonsofthesugarsto
whichtheyareapplied.
-onemayencountersugarsthatareD-(+)orD-(-)andonesthatare
L-(+)orL-(-)
TheDfamilyofaldohexoses
Aldohexoses
Aldopentoses
Aldotetroses
Aldotrioses
Diastereomersdiffering
onlyatthehemiacetalor
acetalcarbonarecalled
anomers,
α-D-(+)-Glucopyranose
Changeinspecific
rotaOontowardan
equilibriumvalueis
calledmutarota*on
(+52.7)
β-D-(+)-Glucopyranose
D-glucoseβ-anomerofaglucopyranoseisthemorestableisomer
D-mannose,theequilibriumfavorstheαanomer,
andthisresultiscalledananomericeffect
Axiallyorientedorbitalassociatedwithnonbondingelectronsofthering
oxygencanoverlapwithaσ*orbitaloftheaxialexocyclicCOhemiacetal
bond.
Whatisresponsiblefortheanomericeffect?
SubsOtuentsintheaxialposiOonhavealonepairontheatom(Z)bondedtothe
ring.Thebondhasaσ*anObondingorbital.
Ifringoxygen’slonepairsisinanorbitalparalleltotheσ*an*bondingorbital,the
moleculecanbestabilizedbyelectrondensityfromoxygenmovingintothe
σ*orbital.
PossiblewhenthesubsOtuentisaxial.
WhensubsOtuentisequatorial,neitheroftheorbitalsthatcontainalonepairis
alignedcorrectlyforoverlap.
Sucrose:Ordinarytablesugarisadisaccharidecalledsucrose,the
mostfoundinallphotosyntheOcplantsandisobtained
commerciallyfromsugarcaneorsugarbeets.
Lactoseisadisaccharidefoundinmilk.LactoseconsOtutes4.5%of
cow’smilkbyweightand6.5%ofhumanmilk.
ArOficialsweeteners
Morestablethan
aspartame
-roughly2000
Omesassweetas
sucrose
•  Aspartame-roughly100Omesassweetassucrose
•  Cannotbeusedforbaking-decomposeswithheat
•  peoplewithageneOccondiOonknownasphenylketonuria
cannotuseaspartame-theirmetabolismcausesabuildup
ofphenylpyruvicacidderivedfromaspartame.
•  Sucraloseis600Omessweeterthansucrose
•  Sucraloselooksandtasteslikesugar,
•  stableatthetemperaturesusedforcooking
andbaking,
•  doesnotcausetoothdecayorprovide
calories.
Starch
α(1è4)linkages
causeitto
assumetheshape
ofale]-handed
helix.
Cellulose
40parallelstrands
ofglucose
moleculeslinkedin
aβ(1è4)fashion
Chi*n
Chi*n
apolysaccharidefound
intheshellsoflobsters
andcrabsandinthe
externalskeletonsof
insectsandspiders
Heparin
Heparin,asulfatedpolysaccharidethat
consistspredominatelyofalternaOng
unitsofD-glucuronate-2-sulfateandNsulfo-D-glucosamine-6-sulfate
Heparinoccursinintracellulargranulesofmastcellsthat
linearterialwalls,where,whenreleasedthroughinjury,itinhibitsthe
clopngofblood.Itspurposeseemstobetopreventrunawayclot
formaOon.Hepariniswidelyusedinmedicinetopreventblood
clopnginpostsurgicalpaOents.
Aminoacidsandproteins
(S)--aminoacid
L-a-aminoacid
EnzymaOcresoluOonof
aminoacids
L-glyceraldehyde
Vasopressinoccursinmalesandfemales-
contracOonofperipheralbloodvesselsandan
Oxytocinoccursonlyinthefemaleofa increaseinbloodpressure.
speciesandsOmulatesuterine
majorfuncOon-an;diure;c;
contracOonsduringchildbirth.
Roleofdisulphides
Insulin
Insulin,ahormonesecretedbythepancreas,regulatesglucose
metabolism.Insulindeficiencyinhumansisthemajorproblemin
diabetesmellitus
Humaninsulindiffersfrombovineinsulinatonlythreeamino
acidresidues:ThreoninereplacesalanineonceintheAchain
(residue8)andonceintheBchain(residue30),and
isoleucinereplacesvalineonceintheAchain(residue10).
Insulinsfrommostmammalshavesimilarstructures.
β-sheet
α-Helix
Humancarbonicanhydrase
Myoglobin
Whenthehemecombineswithoxygen
theferrousiondoesnotbecome
readilyoxidizedtotheferricstate
NucleicAcids
Righthanded
Le]handed