Bioorganic Compounds

1
Bioorganic Compounds
2
Bioorganic Compounds

• Amino Acids Proteins
• Lipids
• Carbohydrates
• Nucleic Acids
• Miscellaneous
• Alkaloids
• Vitamins
• Drugs
• In most cases biological activity depends on
• stereochemistry

3
Stereochemistry
4
Stereochemistry

• Deals with
• Determination of the relative positions in space
  of atoms, groups of atoms
• Effects of positions of atoms on the properties

• Sterical structure
• Constitution
• Configuration
• Conformation

5
Isomers
constitutional isomers
stereoisomers
6
Isomers
constitutional isomers
stereoisomers
diastereomers
enantiomers
7
Chirality

• A molecule is chiral if its two mirror image
  forms are not superposable upon one another.
  ASYMMETRIC!
• A molecule is achiral if its two mirror image
  forms are superposable. SYMMETRIC!

8
Bromochlorofluoromethane is chiral
Cl

• It cannot be superposed point for point on its
  mirror image.

Br
H
F
9
Bromochlorofluoromethane is chiral
Cl
Cl
Br
Br
H
H
F
F

• To show nonsuperposability, rotate this model
  180 around a vertical axis.

10
Another look
11
Chlorodifluoromethaneis achiral

• The two structures are mirror images, but are
  not enantiomers, because they can be superposed
  on each other.

12
The Chirality Center
13
The Chirality Center

• a carbon atom with fourdifferent groups attached
  to it
• also called
• chiral centerasymmetric centerstereocenter
• stereogenic center

14
Chirality and chirality centers

• A molecule with a single chirality center is
  chiral.
• Bromochlorofluoromethane is an example.

15
Chirality CentersOther Than Carbon
16
Silicon
b
b
a
a
d
d
Si
Si
c
c

• Silicon, like carbon, forms four bonds in its
  stable compounds and many chiral silicon
  compounds have been resolved

17
Nitrogen in amines
b
b
a
a
very fast


N
N
c
c

• Pyramidal geometry at nitrogen can produce a
  chiral structure, but enantiomers equilibrate too
  rapidly to be resolved

18
Sulfur in sulfoxides
b
b
a
a
slow


S
S


O_
O_

• Pyramidal geometry at sulfur can produce a
  chiral structure pyramidal inversion is slow
  and compounds of the type shown have been resolved

19
A molecule with a single chirality centermust be
chiral.

• But, a molecule with two or more chirality
  centers may be chiral or it may not.

20
Chiral Allenes

• Allenes of the type shown are chiral

A
X
Y
B
A ¹ B X ¹ Y
Have a stereogenic axis
21
Stereogenic Axis

• analogous to difference between
• a screw with a right-hand thread and one with
  a left-hand thread a right-handed helix and a
  left-handed helix

22
AbsoluteandRelative Configuration
23
Configuration

• Relative configuration compares the arrangement
  of atoms in space of one compound with those of
  another. Until the 1950s, all configurations
  were relative
• Absolute configuration is the precise
  arrangement of atoms in space. We can now
  determine the absolute configuration of almost
  any compound

24
Fisher Projections
Purpose of Fischer projections is to show
configuration at chirality center without
necessity of drawing wedges and dashes or using
models.
25
Rules for Fischer projections
H
Cl
Br
F

• Arrange the molecule so that horizontal bonds at
  chirality center point toward you and vertical
  bonds point away from you.

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Rules for Fischer projections
H
Cl
Br
F

• Projection of molecule on page is a cross. When
  represented this way it is understood that
  horizontal bonds project outward, vertical bonds
  are back.

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O
O
Absolute configuration 1.) D/L system 2.) R/S
system
H
H
H
H
D()-glyceraldehyde
L (-)-glyceraldehyde
D dexter right R rectus L levus
left S sinister
(ox)
(ox)
H
(red)
(red)
D-configuration
L-configuration
28
Configuration of Amino Acids
29
The Cahn-Ingold-Prelog R-S Notational System
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The Cahn-Ingold-Prelog Rules

• 1. Rank the substituents at the stereogenic
  center according to decreasing atomic number.
• 2. Orient the molecule so that lowest-ranked
  substituent points away from you.

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CIP Rules

• (2) When two atoms are identical, compare the
  atoms attached to them on the basis of their
  atomic numbers. Precedence is established at
  the first point of difference.

CH2CH3 outranks CH3
32
CIP Rules

• (3) Work outward from the point of attachment,
  comparing all the atoms attached to a
  particular atom before proceeding
  further along the chain.

CH(CH3)2 outranks CH2CH2OH
C(C,H,H)
C(C,C,H)
33
CIP Rules

• (4) Evaluate substituents one by one. Don't
  add atomic numbers within groups.

CH2OH outranks C(CH3)3
C(O,H,H)
C(C,C,C)
34
CIP Rules

• (5) An atom that is multiply bonded to another
  atom is considered to be replicated as a
  substituent on that atom.

CHO outranks CH2OH
C(O,H,H)
C(O,O,H)
(A table of commonly encountered substituents
ranked according to precedence is given on the
inside back cover of the text.)
35
Example
1
1
17
17
35
35
9
9

• Order of decreasing rank4 of 3 2

clockwise
anticlockwise
S
R
H1 F9 Cl17
Br35
36
Application of C. I. P. rules for Geometric
Isomers

E/Z system
cis
trans
1
2
1
2
2
2
1
1
(Z)-1-Bromo-1-chloro-2-methyl-1-butene
(E)-1-Bromo-1-chloro-2-methyl-1-butene
Zusammen together
Entgegen opposit
37
CIP Rules

• (1) Higher atomic number outranks lower atomic
  number

Br gt F Cl gt H
(Z )-1-Bromo-2-chloro-1-fluoroethene
38
The E-Z Notational System

• E higher ranked substituents on opposite sides
• Z higher ranked substituents on same side

higher
lower
higher
higher
higher
lower
lower
lower
Entgegen
Zusammen
39
Physical properties of enantiomers

• Same melting point, boiling point, density,
  etc
• Different properties that depend on shape of
  molecule (biological-physiological properties)
  can be different

40
Properties of Chiral MoleculesOptical Activity
41
Optical Activity

• A substance is optically active if it rotates
  the plane of polarized light.
• In order for a substance to exhibit
  opticalactivity, it must be chiral and one
  enantiomer must be present in excess of the
  other.

42
Light

• has wave properties
• periodic increase and decrease in amplitude of
  wave

43
Light

• optical activity is usually measured using light
  having a wavelength of 589 nm
• this is the wavelength of the yellow light from
  a sodium lamp and is called the D line of sodium

44
Polarized light

• ordinary (nonpolarized) light consists of
  many beams vibrating in different planes
• plane-polarized light consists of only those
  beams that vibrate in the same plane

45
Polarization of light
46
Rotation of plane-polarized light
47
Specific rotation

• observed rotation (?) depends on the number of
  molecules encountered and is proportional
  to path length (l), and concentration (c)
• therefore, define specific rotation ? as

48
Racemic mixture

• a mixture containing equal quantities of
  enantiomers is called a racemic mixture
• a racemic mixture is optically inactive (? 0)
• a sample that is optically inactive can
  beeither an achiral substance or a
  racemicmixture

49
Optical purity

• an optically pure substance consists exclusively
  of a single enantiomer
• enantiomeric excess one enantiomer
  other enantiomer
• optical purity enantiomeric excess
• e.g. 75 (-) 25 () 50 opt. pure (-)

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Resolution of Enantiomers

• Separation of a racemic mixture into its two
  enantiomeric forms

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Resolution of a racemic modification

• Physical methods
• - Spontaneous resolution
• - Inclusion compounds
• - Chromatography
• Chemical methods
• - Diastereomeric salt formation
• Biochemical methods
• - Enzymatic decomposition

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Strategy
enantiomers
53
Strategy
enantiomers
2P()
diastereomers
54
Strategy
enantiomers
C()P()
2P()
C(-)P()
diastereomers
55
Strategy
C()
enantiomers
P()
C()P()
2P()
C(-)P()
P()
diastereomers
C(-)
56
Resolution of a Racemic Mixture
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Lock and Key Model
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Discrimination of Enantiomers byBiological
Molecules
59
Chiral MoleculeswithTwo Chirality Centers

• How many stereoisomers when a particular
  molecule contains two chiral centers?

60
2,3-Dihydroxybutanoic acid
2
3

• 4 Combinations 4 Stereoisomers

Carbon-2 R R S S Carbon-3 R S R S
61
a -9.5
a 9.5
enantiomers
diastereomers
enantiomers
a -17.8
a 17.8



62
Three stereoisomers of 2,3-butanediol
2R,3R
2S,3S
2R,3S
chiral
chiral
achiral
63
How many stereoisomers?

• maximum number of stereoisomers 2n
• where n number of structural units capable of
  stereochemical variation
• structural units include chirality centers and
  cis and/or trans double bonds
• number is reduced to less than 2n if meso forms
  are possible

64
Cholic acid

• 11 chirality centers
• 211 2048 stereoisomers
• one is "natural" cholic acid
• a second is the enantiomer of natural cholic acid
• 2046 are diastereomers of cholic acid