Rules of the Day
4-23-2023
Click here for a copy of the lectures notes I wrote in class
Click here for a copy of the handouts I used in class today
1. If an aromatic ring is loaded with electron withdrawing groups, it is no longer nucleophilic, but can react as an electrophile. In this case, strong nucleophiles can displace a halogen on an aromatic ring. We will only see one example of this very rare and special reaction, in which 2,4-dinitrofluorobenzene reacts with strong nucleophiles such as amines. This is called nucleophilic aromatic substitution, and is very, very rare compared to electrophilic aromatic substitution reactions.
2. Final Piece of Aromatic Chemisty. Rings with a Bad group are so deactivated that neither the Friedel-Crafts alkylation or acylation will work. However, you can add multiple NO2 groups to the same ring if you run the reaction long and hot enough.
3. THE KEY issue with carbohydrates is stereochemistry. The stereochemistry of carbohydrates are based on (+) D and (-) L glyceradehyde. A D-sugar has the same configuration as (+)-D-glyceraldehyde at the chiral center farthest from the carbonyl group. An L-sugar has the same configuration as (-) -L-glyceraldehyde at the chiral center farthest from the carbonyl group. The best way to see this is with Fisher projections. Click here for a molecule of the day that discusses much of this.
4. With Fisher projections, horizontal is toward you, vertical is away from you. Think of it like a teddy bear hugging you. Aaahhhh.
5. Different stereoisomers of similar carbohydrates can be aldehydes (aldose) or ketones (ketose) and they will have different names and generally have 5 (pentose) or 6 (hexose) carbon atoms.
6. Carbohydrates exist in the cyclic, hemiacetal form in solution. Click here for a second molecule of the day that discusses much of this. These are generally shown as Haworth projections. The mechanism involves the same steps at the hemiacetal formation mechanism you learned in Chapter 16.
7. A new chiral center is created (at the anomeric carbon) as the carbohydrate cyclizes, and the OH group can be axial (alpha equals axial for glucose) or equatorial (beta equals equatorial for glucose). For monosaccharides, these two forms are in equilibrium, and interconversion is catalyzed by acid (mutarotation).
8. Cyclic form carbohydrates form either five (furanose) or six (pyranose) membered rings.
9. Click here for a Carbohydrate Module Video (Module) that summarizes 3) - 8). The material in this video was covered in class and could be on the final.
10. Click here for a second Carbohydrate Module Video (Module) you might find this material interesting, especially for the MCAT, but we did not cover it in class so it will not be on the final.
11. The AIDS virus is a single stranded RNA retrovirus meaning a virus particle is a single strand of RNA surrounded by virus proteins. Once inside host cells, the RNA is reverse transcribed to DNA, that then integrates into the genomes of host cells. After an unknown signal the DNA becomes active and is transcribed to long polyprotein mRNAs. A polyprotein transcript is produced from the mRNA called GAG-POL that is cleaved into functional proteins by the AIDS protease.
12. Enzymes catalyze reactions by 1) having acids, bases and nucleophiles in the active site in exactly the right places in 3-dimensions AND 2) by stabilizing transition state structures.
13. The AIDS protease is an aspartyl protease that uses two carboxylic acid groups and a water molecule to hydrolyze an amide bond at neutral pH and at room temperature.
14. Drugs are designed to interfere with the biochemical steps that are unique to the virus, in particular the reverse transcriptase (RNA to DNA) and AIDS protease steps (cleavage of GAG-POL polyprotein into individual virus proteins).
15. The AIDS protease inhibitors are designed to resemble the key tetrahedral intermediateof the amide hydrolysis reaction while maximizing complementary contacts within the active site.
16. Because the reverse transcriptase step makes a significant number of errors, the HIV genome mutates quickly and the target enzymes (reverse transcriptase and AIDS protease) can become resistant to any one drug, so "cocktails" of several drugs are used to counteract resistance.
17.I believe that developing a treatment for AIDS in about a decade stands alongside getting to the moon as one of this countries great technical achievements. The core ideas behind creating the drug are based on 1) understanding the mechanism of the enzyme reaction to be inhibited, 2) design possible drugs that bind only to the disease target, 3) synthesize then test thousands of derivatives to find the precious few that can be taken as pills and cause minimum side effects, make sure they are safe and effective, then synthesize them in large amounts in pure form, batch after batch.
Homework:
There are no quizzes, readings or homeworks for the rest of the semester! When you are ready, you should start working on the Final Practice Homework problems. You will not turn this in, the answers are also posted already. These problems cover the last material of the course, including some covered in the modules linked immediately above.
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