1. Alcohols Biological Activity Nomenclature Preparation Reactions

2. Some Alcohols

3. Alcohols are Found in Many Natural Products

4. Paralytic Shellfish Poisoning

6. Ethanol: the Beverage

7. Excess NADH can cause Metabolic Problems

8. Methanol: Not a Beverage

9. Synergistic and Metabolic Effects In men, ethanol lowers levels of testosterone (and sperm count) due to lack of enzymes needed for the steroid biosynthesis. The enzyme CYP2E1, which is responsible for converting acetaminophen into liver toxins, is activated by ethanol. Ethanol has a caloric value of 7.1Cal/g (fat has a value of 9 Cal/g). Alcohol can cause a degenerative muscle disease called alcoholic myopathy (3 times more common than cirrhosis).

10. Synergistic Effects Women will have higher BAL’s with the consumption of an equal number of drinks due to lower ADH activity and lower % H 2 O in blood. Estradiol levels increase in women (and men). This has been associated with higher incidences of heart disease and a change in bone density. A higher than normal concentration of Cytochrome P-450 enzymes (in the liver) are activated by ethanol creating a potential dependency.

11. Antitumor Agents Often functionalized with alcohols Designed to fit into specific geometic sites on proteins Hydrogen bonding is crucial for binding Water solubility is crucial for cell membrane transport

12. From the Bark of the Pacific Yew Tree Taxol (Paclitaxel)

13. How Taxol Works A large number of microtubules are formed at the start of cell division, and as cell division comes to an end, these microtubules are normally broken down into tubulin – a protein responsible for the cell ’ s structural stability. Taxol promotes tubulin polymerization then binds to the microtubules and inhibits their depolymerization back into tubulin. The cell can't divide into daughter cells and therefore the cancer can ’ t spread.

14. Tubulin with Taxol bound to one of the Functional Domains CHIME diagram of tubulin CHIME diagram of tubulin

15. Taxol Causes Cells’ Tubulin Skeleton to Aggregate in Spindles

16. May be More Effective than Taxol

17. DNA Cross-linker

18. Prevents DNA from Unraveling

19. Oxidation and Reduction 3 hydrocarbon oxidation levels

20. Oxidation levels of oxygen- halogen- and nitrogen- containing molecules

22. Acidity of Alcohols Due to the electronegativity of the O atoms, alcohols are slightly acidic (pKa 16-18). The anion dervived by the deprotonation of an alcohol is the alkoxide. Alcohols also react with Na (or K) as water does to give the alkoxide (red-ox):

23. Withdrawing Groups Enhance Acidity alcoholpKa CH 3 OH15.54 CH 3 CH 2 OH16.00 CF 3 CH 2 OH12.43 (CH 3 ) 3 COH18.00 (CF 3 ) 3 COH 5.4

24. Physical Properties CH 3 CH 2 CH 3 -42 0.08 i CH 3 OCH 3 -251.3 ss CH 3 CH 2 OH781.7 vs b.p. o C  Dsol. in H 2 O

25. Intermolecular H-Bonding

26. Alcohol Nomenclature

27. Nomenclature

28. Who am I?

30. Preparation of Alcohols Reduction of ketones and aldehydes Reduction of esters and carboxylic acids Hydration of Alkenes Nucleophilic addition –Grignard reaction –Acetylide addition Substitution Epoxide opening

31. NaBH 4 Reduction

32. Some Examples

33. Two Alcohol Products Form in Lab

34. LiAlH 4 Reduction a Stronger Reducing Agent

35. LiAlH 4 is a much stronger reducing agent

36. NaBH 4 is More Selective

37. Oxymercuration Hydration Markovnikov

38. Hydroboration Hydration Anti-Markovnikov

39. Organometallic Chemistry Grignard Reaction

40. Grignard Reagents React With Ketones to form tertiary alcohols

41. Grignard Reagents React With Aldehydes to form secondary alcohols

42. Grignard Reagents React With Formaldehyde to form primary alcohols

43. Grignard Reagents open Epoxides

44. Grignard Reagents react (twice) with Esters to form 3 o Alcohols

45. Grignard Summary

47. Grignard Reagents are exceptionally strong bases

48. An Effective Use of the Basicity Isotopic Labeling

49. Synthesis

50. Retrosynthetic Analysis

51. 4-Step Synthesis

52. Base Catalyzed Ring-Opening of Epoxides

53. Base Opens Ring from Unhindered Side

54. Acid Catalyzed Ring-Opening Aqueous and in Alcohol

55. Regiochemistry Ring Opens at More Hindered Site

56. Different Regiosomers

57. Propose a Mechanism

58. 2 S N 2 steps

59. Propose a Mechanism

61. Ring-Opening is Sterically Controlled

62. Synthesize Using Only 1,2, or 3-Carbon Reagents

63. Retrosynthesis