1. Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned in order to fully communicate and understand the concepts.

3. Definitions Stereoisomers – compounds with the same connectivity, different arrangement in space Enantiomers – stereoisomers that are non- superimposible mirror images; only properties that differ are direction (+ or -) of optical rotation Diastereomers – stereoisomers that are not mirror images; different compounds with different physical properties

4. More Definitions Asymmetric center – sp 3 carbon with 4 different groups attached Optical activity – the ability to rotate the plane of plane –polarized light Chiral compound – a compound that is optically active (achiral compound will not rotate light) Polarimeter – device that measures the optical rotation of the chiral compound

5. Plane-Polarized Light

6. Plane-Polarized Light through an Achiral Compound

7. Plane-Polarized Light through a Chiral Compound

8. Polarimeter Measures Optical Rotation

9. Specific Rotation, [α] [α] = α / cl  = observed rotation c = concentration in g/mL l = length of tube in dm Dextrorotary designated as d or (+), clockwise rotation Levorotary designated as l or (-), counter- clockwise rotation

10. Specific Rotations of some Common Organic Compounds Compound[  ]# * centers Penicillin V +233.03 Sucrose +66.5 10 Camphor +44.32 MSG +25.51 Cholesterol -31.38 Morphine -132.05

11. Chirality Center Carbon has four different groups attached

12. Enantiomers nonsuperimposible mirror images

13. Enantiomeric Excess (Optical Purity)

15. Biological Activity

16. SSRI Efficacy depends on Stereochemistry Lexapro® and Celexa® are both prescription medications classified as selective serotonin reuptake inhibitors, licensed to treat depression.

17. Absolute Configuration

18. Assign Priority to each Group on Asymmetric Center

19. Lactic Acid

20. C.I.P. Priorities

21. Fischer Projections

22. Assigning Absolute Configuration to Fischer Projections

23. Rotation of the Projection 90 o Reverses Absolute Configuration

24. Exercise: (1)Assign R/S configurations to the ff molecules: (2)Draw a tetrahedral representation of (S)-2- hydroxypentane.

25. Lexapro and Celexa are formulations of an anti-depressant drug. Celexa was available first and is a mixture of R and S enantiomers of citalopram. Lexapro is just the S enantiomer of citalopram. Draw the molecular structure of each enantiomer.

26. Celexa was available first and is a mixture of R and S enantiomers of citalopram. Lexapro is just the S enantiomer of citalopram. Which one is Lexapro? Which one is Celexa?

27. Diastereomers Stereoisomers That Are Not Mirror Images

28. Fischer Projections with 2 Chiral Centers

29. 2 Chiral Centers 4 Stereoisomers

31. Identical, Enantiomers or Diastereomers?

32. Tartaric Acids

33. Racemic Mixture

34. Meso Compound Internal Plane of Symmetry Optically Inactive

35. 2,3,4-trichlorohexane How many stereoisomers?

36. n = 3; 2 n = 8

37. A Carbohydrate

38. Internal Planes of Symmetry

39. Asymmetric Centers on Rings

40. Which are meso compounds?

41. Reactions that Generate Chirality Centers Hydrogenation, syn

42. Bromination Trans is formed exclusively No Meso is formed (cis)

43. Bromonium Ion is Opened Equally from Both Sides

44. trans alkene + anti addition = MESO

45. cis Alkene + anti addition = racemic mixture

46. Brominations Often Generate Asymmetric Centers

47. Asymmetric Center is Generated Racemic Mixture Formed

48. Asymmetric Induction

49. Preparation of (L)-Dopa for Treatment of Parkinson’s

50. Relevance of Stereochemistry

51. One-step synthesis

52.  -(p-isobutylphenyl)propionic acid

53. Model of Thalidomide

54. How Sweet it is! Sucralose is 600 times sweeter and does not get metabolized.

55. Sildenafil (Viagra) and Caffeine

56. Radiosensitizer of Choice Until 2004