Alcohols Biological Activity Nomenclature Preparation Reactions
Some Alcohols
Alcohols are Found in Many Natural Products
Paralytic Shellfish Poisoning
Ethanol: the Beverage
Excess NADH can cause Metabolic Problems
Methanol: Not a Beverage
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).
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.
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
From the Bark of the Pacific Yew Tree Taxol (Paclitaxel)
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.
Tubulin with Taxol bound to one of the Functional Domains CHIME diagram of tubulin CHIME diagram of tubulin
Taxol Causes Cells’ Tubulin Skeleton to Aggregate in Spindles
May be More Effective than Taxol
DNA Cross-linker
Prevents DNA from Unraveling
Oxidation and Reduction 3 hydrocarbon oxidation levels
Oxidation levels of oxygen- halogen- and nitrogen- containing molecules
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):
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
Physical Properties CH 3 CH 2 CH i CH 3 OCH ss CH 3 CH 2 OH781.7 vs b.p. o C Dsol. in H 2 O
Intermolecular H-Bonding
Alcohol Nomenclature
Nomenclature
Who am I?
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
NaBH 4 Reduction
Some Examples
Two Alcohol Products Form in Lab
LiAlH 4 Reduction a Stronger Reducing Agent
LiAlH 4 is a much stronger reducing agent
NaBH 4 is More Selective
Oxymercuration Hydration Markovnikov
Hydroboration Hydration Anti-Markovnikov
Organometallic Chemistry Grignard Reaction
Grignard Reagents React With Ketones to form tertiary alcohols
Grignard Reagents React With Aldehydes to form secondary alcohols
Grignard Reagents React With Formaldehyde to form primary alcohols
Grignard Reagents open Epoxides
Grignard Reagents react (twice) with Esters to form 3 o Alcohols
Grignard Summary
Grignard Reagents are exceptionally strong bases
An Effective Use of the Basicity Isotopic Labeling
Synthesis
Retrosynthetic Analysis
4-Step Synthesis
Base Catalyzed Ring-Opening of Epoxides
Base Opens Ring from Unhindered Side
Acid Catalyzed Ring-Opening Aqueous and in Alcohol
Regiochemistry Ring Opens at More Hindered Site
Different Regiosomers
Propose a Mechanism
2 S N 2 steps
Propose a Mechanism
Ring-Opening is Sterically Controlled
Synthesize Using Only 1,2, or 3-Carbon Reagents
Retrosynthesis