Lecture chem
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Transcript of Lecture chem
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1Importance of stereochemistry Enantiomers have identical chemical and physical properties Differ - rotating polarised light
....... ..- interaction with other chiral molecules Important in biology...
Me2NMe
Ph O
EtO
darvon
Darvon is a painkiller.
Its enantiomer is an anticough agent.
R R
enzyme
X
only one enantiomer matches chiral enzyme
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2Polarised light Ordinary light has EM radiation oscillating in all possible planes (3 shown) Polarised light is in a single plane
CO2H
H NH2
measure rotationderive []D = +14
CO2H
H2N H
measure rotationderive []D = -14
ordinary light polarised light
Chiral compounds rotate polarised light. A pair of enantiomers rotate the plane of polarised light by equal amounts in opposite directions. A 1:1 mixture of enantiomers does not rotate light and is called a racemate
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3Diastereoisomers I Cyclic compounds can exist as diastereoisomers Diastereoisomers differ by the spatial orientation of atoms Can have very different physical properties Do NOT have to be chiral (if they have a plane of symmetry)
OH
OH
OH
OH
diastereoisomersidentical identical
OH
molecule has a plane of symmetry
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4Diastereoisomers II
2 stereocentres can result in FOUR compounds (4 diastereoisomers) No plane of symmetry chiral & 2 pairs of enantiomers (mirror images) 2 enantiomeric pairs - each enantiomer has identical physcial properties But diastereoisomers have different physical properties Enantiomers have same relative stereochemistry but different absolute
stereochemistry
O
CO2Me
O2N
O
CO2Me
O2N
O
CO2Me
O2N
O
CO2Me
O2N
diastereoisomersenantiomersenantiomers
trans epoxide
mp = 141Ccis
epoxidemp = 98C
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5Diastereoisomers III
If a molecule has 3 stereocentres then it has potentially 8 stereoisomers (4 diastereoisomers & their enantiomers) If a molecule has n stereocentres then potentially 2n stereoisomers But if a molecule has a plane of symmetry it wil be less...
HOCHO
OH
OH OH
(2S,3S,4S)-ribose
(2R,3R,4R)-ribose (2R,3R,4S)-arabinose
(2S,3S,4R)-arabinose
(2R,3S,4R)-xylose
(2S,3R,4S)-xylose
(2R,3S,4S)-lyxose
(2S,3R,4R)-lyxose
HOCHO
OH
OH OH
HOCHO
OH
OH OH
HOCHO
OH
OH OH
HOCHO
OH
OH OH
HOCHO
OH
OH OH
HOCHO
OH
OH OH
HOCHO
OH
OH OH
HOCHO
OH
OH OH
ribose(2R,3R,4R)-2,3,4,5-tetrahydroxypentanal
fourdiastereomers
and their 4 enantiomers
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6HO2C CO2HOH
OH
tartaric acid
Meso compounds I
2 stereocentres so 4 stereoisomers? There are 2 diastereoisomers - one has an enantiomer
...................................na......... - the other does NOT
HO2C CO2HOH
OHHO2C CO2H
OH
OH
HO2C CO2HOH
OHHO2C CO2H
OH
OH
diastereoisomersenantiomers identical
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7Meso compounds II
Meso compounds - compounds containing stereocentres but are still achiral Meso compounds have a plane of symmetry with (R) configuration
on one side and (S) on the other
Two compound on previous slide identical as rotation below shows...
HO2C CO2HOH
OHHO2C CO2H
OH
OH
HO2C CO2HOH
OH
HO2C
CO2H
OHHO
CO2HHO2C
OH
OHrotate around central axis
HO2C
CO2HHO
OH
rotate LHS
Even though compound has TWO stereocentres it is ACHIRAL It is achiral because it has a plane of symmtery...
HO2C
OH
CO2H
HO
mirror plane
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8H OH
() or (R) / (S)racemate
Resolution
Enantiomers physically the same - diastereoisomers are not!
+HO2C Ph
OMe
HO
O
OMe
Ph + O
O
OMe
Ph
2 diastereoisomers (hopefully separable)
React 2 chiral compounds to form diastereoisomers Separate these (if possible)
NaOHH2O
NaOHH2O
OH OH
pure (S) pure (R)
Regenerate required compound
Separation of enantiomers is ..called resolution
If you can't synthesise it pure ..how do you purify enantiomers?
We need enantiomerically pure ..compounds
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9Chirality in nature I
Insulin is made of 2 peptide chains - 1x30 amino acids & 1x21 amino acids Potentially 2.25 x 1015 diastereoisomers A relatively small protein is ribonuclease at 124 amino acids or Potentially 2.13 x 1037 diastereoisomers
Natural amino acids are enantiomerically pureThese are the building blocks of proteins and enzymes
HO2C Me
NH2
HO2C
NH2
HO2C
NH2 N
HN
alanine phenylalanine histidine
Why this enantiomer? Who knows...But why just one enantiomer is more obvious...
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10
Chirality in nature II
Enantiomers are identical except their interaction with polarised light and other chiral molecules (like our bodies) This can have trivial effects...like smell / taste
HO OH
ON
OP
OP
OP
HO
N
N
N
NH2
OHOOHOOHO
adenosine triphosphate ATP
O
HO
N
NH
O
OHO
thymine derivative of deoxyribonucleic acid
(DNA)
O
HO OH
NHO
N
N
NH
O
NH2
guanine derivative of ribonucleic acid (RNA)
Nucleosides are enantiomerically pureThese are the basis of all life via DNA and / or RNA
Also ATP which is the main sourse of energy in our cells
O
H
(R)-carvonespearmint
(R)-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-enone
O
H
(S)-carvonecaraway
(S)-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-enone
H
(S)-limonenelemons
(S)-1-methyl-4-(prop-1-en-2-yl)cyclohex-1-ene
H
(R)-limoneneoranges
(R)-1-methyl-4-(prop-1-en-2-yl)cyclohex-1-ene
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11
Chirality in nature III
Drugs frequently need to be optically pure (R)-Thalidomide is a sedative - (S) isomer cause birth defects Dextromethorphan is a cough suppresant Levomethorphan (its enantiomer) is a narcotic Top two drugs were Lipitor and Zucor and are single enantiomers They generated $14 billion in 2002 Single enantiomer drugs worth $159 billion in 2002 Big buisiness!
N
S
O
HNR
O
H H
CO2H
penicillin skeleton
O
N
N
NH
O
OHO
NN
AZTazidothymidine
NH
O O
HN
O
O
(R)-thalidomideOMe
HN
dextromethorphan
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12
Other forms of chirality
It is not necessary for a compound to have a tetrahedral stereocentre to be a chiral compound!!
(Rp)-4-amino[2.2]para-
cyclophane
(Sp)-4-amino[2.2]para-
cyclophanemirror plane
NH2 H2N
PPh2PPh2
(S)-BINAP2-(diphenylphosphino)-1-((S)-2-
(diphenylphosphino)naphthalen-1-yl)naphthalene
Ph2PPh2P
(R)-BINAP2-(diphenylphosphino)-1-((R)-2-
(diphenylphosphino)naphthalen-1-yl)naphthalene
mirror plane
full rotation impossible
axial chirality
planar chirality