The Last Lecture
Today we finished up by looking at the transamination reaction between alanine and alpha keto glutarate. The lesson was, as always, to show that complicated biological processes can typically be reduced to a series of elementary organic reactions.
To get your own copy of the biochemical processes wall poster that I showed in class, go to
this web site and click on the link at the bottom.
Keys have been posted.....
I have placed keys to exams 1, 2, and 3 to the right to go with the key to exam 4. Remember, Meaghen will have final exam review sessions on Saturday (1:30 - 3:30) and Sunday (6 - 8) in the Althouse lounge.
There is also a set of practice multiple choice questions.
Nucleic Acids
As we work our way to the end of the semester we are looking at bits and pieces of various topics. Today we looked at how ribose (or deoxyribose), sugars and ATP as a phosphoric acid equivalent can be used to make nucleic acids. It is just stringing together a number of known reactions.
Meaghen will hold two group study sessions this weekend: Saturday from 1:30 - 3:30 and Sunday from 6 - 8. Both sessions will be held in the Althouse lounge.
The class ended with a brief tutorial on polonium poisoning.
Pyridine, an Odd Aromatic Compound
Today we talked about pyridine, a somewhat strange aromatic compound. Pyridine is essentially a benzene ring with an sp2-hybridized nitrogen replacing one of the carbon atoms. With six ring electrons, the system is aromatic but the lone pair of electrons on the nitrogen is NOT part of the aromatic system. This gives pyridine more basicity than aromatic amines. However, since the orbital holding the lone pair is an sp2, with more s-character than the sp3-hybridized orbitals of aliphatic amines, pyridines hold the lone pair closer to the nuclei and are therefore less basic than aliphatic amines.
It is possible to perform EAS reactions on pyridine, with the electrophile ending up on the carbon with the largest partial negative charge (two carbons from the nitrogen, you can think of it as a sort of "meta" position). The reaction is typically of poor yield, as the nitrogen lone pair has a tendency to interact with the electrophile, not giving it a good opportunity to react with the ring.
A better reaction is the NAS (Nucleophilic Aromatic Substitution) of 2-halo pyridines. The electronegativity of the nitrogen allows for stabilization of the anionic intermediate, making the process viable.
New Items Added
An
answer key and
Need to Knows for Chapters 27 and 28 have been added to the links to the right.
A "Two-fer" entry
Today's entry is a two-for-one special, covering Monday's class and today.
On Monday we covered a portion of Chapter 27 and learned how to create terpenoids, or molecules that are derived from the combination of functional equivalents of isoprene. The processes that we saw are generally reactions that we know (Claisen, aldol, decarboxylation, loss of water to make stable carbon cations, etc.) with one new reaction thrown in: the use of NADH or NADPH as a hydride source. We also saw that it is possible to create a wide variety of different terpenoids by rearranging the structures.
Today was exam #4, hopefully it went well for everyone. I won't be able to start grading them until tomorrow so at this point my guess is that they will be ready to be returned on Monday.
New Items for the Blog
I have posted a number of new items to the right. First, I finally put up the answer key to ps 14. There is also a new problem set, ps 16, dealing with the synthesis of peptides from amino acids. The answer key to last year's Exam 4 is also posted. Finally, there is a link for extra problems for topics covered on this exam. I was putting together a compilation of problems from other texts for a student and decided to post it for everyone in the class. It is a low-tech cut and paste job, so it looks something like a ransom note, but it is at least a source of more problems for you to do. I will work on putting together an answer key for it, but no promises until the beginning on next week.
Peptides!
Today we learned how to couple two amino acids to make a peptide. Although complicated on the surface, note that it is possible to make a peptide of any length by repeating the steps over (and over and over and over.....). The basic concepts are that it is necessary to protect various nitrogens and carboxylic acid fragments, then activate other sites. All of this is covered pretty well on the podcast that you can download from the link at right or by subscribing to the feeds on iTunes, as mentioned in the previous post. This finished our coverage of material that is on the next exam, to be given on November 29.
Have a great Thanksgiving!
Subscribing to Podcasts
An easy way to access the podcasts is to subscribe to them through iTunes. This way you will always have access to the files and they will open in iTunes; with "Show Artwork" selected you'll be able to hear and see them. (Remember to drag the windows to maximize the size of the artwork. Some versions of iTunes will show the pictures full screen if you click on them, some will show the current picture but will not change them as the podcast goes along.) It is easy to do this: Just open iTunes and under the "Advanced" menu select "Subscribe to Podcast" and enter the following URL:
http://itech.dickinson.edu/blog/?feed=rss2&cat=765
You can then download the podcasts at will. You will be able to access them by selecting "Podcasts" under the "Library" menu at the left-hand side of the iTunes window. The podcast to which you have subscribed will be titled "Dickinson College Blog."
More Amino Acid Material
Today we started with an example of how enantioselective synthesis can be an effective technique for manufacturing amino acids. The trick is to introduce some optically active element into the reaction in such a way that only (or mostly) one of the possible developing chiral centers is formed.
Most of the class was centered around determining the amino acids present in a peptide. The total array of amino acids can easily be determined by hydrolysis and then isolating each of the resultant amino acids. However, to determine the correct order in which they are aligned, it is necessary to do something much more interesting, such as an Edman degradation. In this process, the N-terminal amino acid is removed from the rest of the peptide and incorporated into a heterocyclic compound. This compound is unique for each amino acid and therefore it is trivial to identify the N-terminal amino acid. Even better, the rest of the peptide remains intact so that the next amino acid in line becomes the new N-terminal amino acid and so the process can be repeated all the way down the line, identifying each amino acid in order.
An Amino Acid Primer
Today was the start of Chapter 26, in which we study amino acids and the compounds they make. There was a great deal of factual information today, including some basic nomenclature. We also saw the basic structure of peptides (in which amino acids are strung together in a chain) and made a note on how the peptide bond has limited ability to rotate. Finally, we saw how to draw amino acids as Fischer projections, in the standard biochemist's configuration.
We spent the last part of the lecture looking at how to synthesize amino acids; here we saw a number of familiar reactions including the Hell-Volhard-Zelinski and Gabriel reactions, a variant of the malonate ester synthesis called the amidomalonate synthesis (with alkylation, hydrolysis, and decarboxylation steps) and reductive elimination. The problem with all of these is that the product amino acids are racemic. I showed how to resolve the mixture into separable diastereomers by treatment with a chiral base but you are still wasting half of the product if you do that. On Friday our first subject will be how to create a single chiral center with no waste of materials.
Finishing up carbohydrates.....
Today was the final day for carbohydrate material. We first looked at pictures of D-galactose to see how it is possible to go from a Fischer projection of a carbohydrate to a chair conformation with correct stereochemistry. (Remember, you'll need to go back and make sure that you can draw chair configurations!) We then finished up by showing that the -OH group on the anomeric position is the one that is reactive under acidic conditions. Finally, it was shown how this reactivity leads to the formation of complex carbohydrates and also the decomposition of complex carbohydrates into simple carbohydrates.
There were a number of announcements including the news that three candidates for a chemistry/B&MB faculty position will be interviewing over the next several weeks. The first candidate, John Magyar, will be on campus this Wednesday. His research seminar will be at 11:30 on Wednesday in Althouse 4, and his teaching seminar will be at 1:30 in Althouse 5. Please mark your calendars and try to attend one or both, I will be anxious to get student feedback.
The other two candidates will be arriving soon: Danielle Dube will be here on Monday, November 20 (research seminar at 11:30, teaching seminar at 3:00) and Jessica Alexander will be on campus Friday, December 1 (research seminar at 11:30 and teaching seminar at 3:00).
Chapter 26 starts on Wednesday. W = 26.1, 3-6; F = 26.7-9; M = 26.10, W = prepare to eat turkey (and sweet potato pie)!
Fischer Projections
Today's main point was the Fischer projection. This biochemist's way of drawing three-dimensional carbon atoms is useful but a little awkward at first. Essentially, it reduces down to a few basics: horizontal lines are coming out at you and vertical lines are going back away from you; 180° rotations give you the same molecule; 90° rotations give you the mirror image (and therefore the enantiomer if there are four distinct substituents on the carbon); holding one substituent in place and rotating the other three (either CW or CCW) gives you the same thing. We looked at the method for determining R and S configurations -- put priority #4 at the top by whatever manipulation you need and then look for CW (R) or CCW (S) rotation of 1, 2 and 3.
At the end we started looking at how carbohydrates form six-membered rings and I left you with an assignment for the weekend -- make a model of D-galactose and orient it into position to make a six-membered ring. See if you can determine any relationship between the positions of the -OH groups in the Fischer projections and the orientations of the -OH groups in the chair conformation.
I've added a link for podcasts to the right. I'll talk more about them on Monday.
There are also links for two new problem sets, 14 and 15. There is no key for 14 yet (we haven't talked about all of the material), ps 15 is all about relating two Fischer projections to one another.
A Fitting Conclusion to Amines
Today we finished amines by discussing two concepts. The first was the EAS reaction on aromatic amines; after a false start the class agreed that an amino groups should be considered to be an o,p-directing, activating substituent. The problem is that it is too activating and leads to polysubstitution. The problem can be rectified by doing some carboxylic acid derivative chemistry -- convert the amine to an amide by reacting with an anhydride or acid halide to lessen the electron donating ability of the nitrogen. Following the EAS (with only a single substitution) the amide can be hydrolyzed, regenerating the amine.
The second topic was the Sandmeyer process. Through a sequence of steps analogous to the formation of a nitronium ion, it is possible to convert HNO2 to an N=O cation. This electrophile reacts not with the ring but instead with the nitrogen of an aromatic amine; loss of water leads to a salt. A complex and not well understood substitution will take place with a number of nucleophiles, leading to removal of the nitrogen and replacement with the nucleophile.
We had a brief start to chapter 25. The subject is carbohydrates. Mostly we talked about some basic nomenclature but on Friday we will start actual chemistry. We'll need to understand the biochemist's way of drawing tetrahedral carbons (Fisher projections), so bring your models on Friday!
There is a new video of the week. If you like things blowing up in microwaves, you'll like the video.
Rearrangements
Yesterday was a rearrangement day. We spent nearly all of the class period going over the Curtius and the Hofmann rearrangements. The key to each is that a leaving group is attached to a nitrogen atom -- heat (energy) allows the compound to undergo the desired rearrangement. It is important that you understand these mechanisms, and the similarities between them.
We also touched on the Hofmann elimination. In this example, Hofmann took advantage of the ability of a nitrogen to "overalkylate" and obtain a positive charge. Such an atom is a good leaving group and with clever use of (non-nucleophilic) base an elimination reaction can take place.
Tomorrow we will finish up Chapter 24 by looking at some chemistry of aromatic amines and hopefully start Chapter 25.
