1. Bioorganic Compounds 1

2. In most cases biological activity depends on stereochemistry
Bioorganic Compounds
Amino Acids – Proteins
Lipids
Carbohydrates
Nucleic Acids
Miscellaneous
Alkaloids
Vitamins
Drugs
In most cases biological activity depends on
stereochemistry

3. Stereochemistry 1

4. Deals with: Sterical structure: Stereochemistry
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 8

6. Isomers constitutional isomers stereoisomers enantiomers diastereomers8

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! 3

8. Bromochlorofluoromethane is chiralCl
It cannot be superposed point for point on its mirror image. Br H F 4

9. Bromochlorofluoromethane is chiralCl Cl Br Br H H F F
To show nonsuperposability, rotate this model 180° around a vertical axis. 4

10. Another look 6

11. Chlorodifluoromethane is achiral
The two structures are mirror images, but are not enantiomers, because they can be superposed on each other. 9

12. The Chirality Center 11

13. a carbon atom with four different groups attached to it also called:
The Chirality Center
a carbon atom with four different groups attached to it
also called:
chiral center asymmetric center stereocenter
stereogenic center w x y z C 12

14. Chirality and chirality centers
A molecule with a single chirality center is chiral.
Bromochlorofluoromethane is an example. Cl F Br H C 13

15. Chirality Centers Other Than Carbon1

16. Silicon b b a a Si d d Si c c
Silicon, like carbon, forms four bonds in its stable compounds and many chiral silicon compounds have been resolved 6

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 6

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 6

19. A molecule with a single chirality center must be chiral.
But, a molecule with two or more chirality centers may be chiral or it may not. 18

20. Allenes of the type shown are chiral
Chiral Allenes
Allenes of the type shown are chiral A X C B Y
A ¹ B; X ¹ Y
Have a stereogenic axis 25

21. analogous to difference between:
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 26

22. Absolute and Relative Configuration14

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 15

24. Fisher Projections
Purpose of Fischer projections is to show configuration at chirality center without necessity of drawing wedges and dashes or using models. 1

25. Rules for Fischer projectionsBr Cl F
Arrange the molecule so that horizontal bonds at chirality center point toward you and vertical bonds point away from you. 13

26. Rules for Fischer projectionsBr Cl 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. 13

27. Absolute configuration:
1.) D/L system
2.) R/S system C HO OH H 2 O H H H H
D(+)-glyceraldehyde
L (-)-glyceraldehyde
D = dexter = right = R = rectus
L = levus = left = S = sinister C H X
(ox)
(ox) H
(red)
(red)
D-configuration
L-configuration

28. Configuration of Amino Acids

29. The Cahn-Ingold-Prelog
R-S
Notational System 1

30. 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. 4

31. 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
—C(C,H,H)
—C(H,H,H) 24

32. —CH(CH3)2 outranks —CH2CH2OH
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,C,H)
—C(C,H,H) 25

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) 26

34. CIP Rules
(5) An atom that is multiply bonded to another atom is considered to be replicated as a substituent on that atom.
—CH=O 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.) 27

35. Order of decreasing rank 4 ® of 3 ® 2
Example 1 1 17 17 35 35 4 3 2 1 4 3 2 1 9 9
Order of decreasing rank 4 ® of 3 ® 2
clockwise
anticlockwise R S
H= F= Cl= Br=35 5

36. Application of C. I. P. rules for Geometric Isomers
E/Z system
cis
trans 1 2 2 1 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. (1) Higher atomic number outranks lower atomic number
CIP Rules
(1) Higher atomic number outranks lower atomic number
Br > F Cl > H
higher
lower Br F Cl H C
(Z )-1-Bromo-2-chloro-1-fluoroethene 23

38. The E-Z Notational System
E : higher ranked substituents on opposite sides
Z : higher ranked substituents on same side
higher
lower
higher
higher C C
lower
higher
lower
lower
Entgegen
Zusammen 21

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 11

40. Properties of Chiral Molecules: Optical Activity1

41. Optical Activity
A substance is optically active if it rotates the plane of polarized light.
In order for a substance to exhibit optical activity, it must be chiral and one enantiomer must be present in excess of the other. 2

42. periodic increase and decrease in amplitude of wave
Light
has wave properties
periodic increase and decrease in amplitude of wave 3

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 4

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 5

45. Polarization of light
Nicol prism 6

46. Rotation of plane-polarized light 7

47. therefore, define specific rotation [] as:
observed rotation () depends on the number of molecules encountered and is proportional to: path length (l), and concentration (c)
therefore, define specific rotation [] as:
100  cl
concentration = g/100 mL
length in decimeters
[] = 8

48. a racemic mixture is optically inactive ( = 0)
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 be either an achiral substance or a racemic mixture 9

49. enantiomeric excess = % one enantiomer – % other enantiomer
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 (-) 10

50. Resolution of Enantiomers
Separation of a racemic mixture into its two enantiomeric forms 1

51. Resolution of a racemic modification
Physical methods:
- Spontaneous resolution
- Inclusion compounds
- Chromatography
Chemical methods:
- Diastereomeric salt formation
Biochemical methods:
- Enzymatic decomposition

52. Strategy
enantiomers
C(+)
C(-) 11

53. Strategy enantiomers C(+) C(-) 2P(+) C(+)P(+) C(-)P(+) diastereomers11

54. Strategy enantiomers C(+) C(-) C(+)P(+) 2P(+) C(-)P(+) C(+)P(+)
diastereomers 11

55. Strategy enantiomers C(+) C(+) C(-) P(+) C(+)P(+) 2P(+) C(-)P(+)
diastereomers
C(-) 11

56. Resolution of a Racemic Mixture
(S)-base
(R)-acid (S)-acid
enantiomers
(R,S)-salt (S,S)-salt
diastereomers
(R,S)-salt
(S,S)-salt
HCl
(S)-baseH+ +
(R)-acid
(S)-acid

57. Lock and Key Model

58. Discrimination of Enantiomers by Biological Molecules

59. Chiral Molecules with Two Chirality Centers
How many stereoisomers when a particular molecule contains two chiral centers? 10

60. 2,3-Dihydroxybutanoic acid
CH3CHCHCOH HO OH 3 2
4 Combinations = 4 Stereoisomers
Carbon-2 R R S S
Carbon-3 R S R S 6

61. R S R S R S HO CO2H CH3 H OH CO2H CH3 H HO OH [a] = -9.5° [a] = +9.5°
enantiomers
diastereomers
CO2H H
CH3 HO R S
CO2H
CH3 H OH R S
enantiomers
[a] = +17.8°
[a] = -17.8° 12

62. Three stereoisomers of 2,3-butanediolOH
CH3 HO
CH3 OH H HO H
CH3 OH
2R,3R
2S,3S
2R,3S
chiral
chiral
achiral 6

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 24

64. Cholic acid HO OH H H3C CH2CH2COOH CH3 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 26