methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside 2-(dihydrogen phosphat

Man, the name can't even fit in the title field! Maybe the structure will help. I caught me a nasty bug in my leg that's been growing ever since turkey day and this bad boy is trying to keep it in check. Unfortunately it doesn't look like it's doing a very effective job. I may need to get it in IV form. More and more antibiotic resistant bacteria are making an appearance. Get out there and discover some new drugs. Please! By the way, this one tastes like shit. I am pumped so full of it I can taste it oozing out into my mouth.

Hope you all had a better holiday.

Let's Talk Turkey

It is only a couple days away from the Thanksgiving holiday here in America. I love it. A whole day dedicated to stuffing a bird then stuffing yourself full of fats, carbs, and tryptophan. We get to laze around on the couch watching football and make serotonin out of that gobbler. Yes, eating turkey is thought to increase the amounts of this wonderful neurotransmitter and make you sleepy. Of course tryptophan is also the starting material for the production of melatonin, another inducer of drowsiness. Personally I think it is more likely that all the beer and wine being consumed is what leads to thanksgiving day couch potato syndrome. By the way, a recent study reported in the Journal of the Science of Food and Agriculture (that one is on everyone's daily reading list, no?) indicates that red wines have a significant amount of melatonin.

Gone but not forgotten

Albert I. Meyers
November 22, 1932 - October 23, 2007

I was deeply saddened to hear that Al has passed away. He has been an inspiration to me for a long time. A genuinely nice man, he always encouraged students and colleagues to fulfill their potential. I remember as a young graduate student giving my first talk at an ACS meeting how nervous I was. Afterward Al came up to introduce himself and tell me what a good job I had done. Thanks Al, that did more for my confidence than anything else in my career. Organic Chemistry lost a great one this week. Rest in peace, Al.

Happy Mole Day

Happy Holiday Everyone! I think we all need to take the day off and spread the good word about Avogadro. Is anyone else celebrating?

IBX (not Irritable Bowl Xyndrome)

I really like oxidation reactions but, for some reason, many students get confused about how they work. It's not really different than any other reaction. It's just electrons moving from one place to another. The problem is that we usually think it is weird to push electrons toward an oxygen at the same time break electrons off of an oxygen. However, in nearly every oxidation of alcohols, this is happening. Of course the requirement is that you have something attached to the oxygen that is more electrophilic. For example, highly oxidized Cr or S or, in the case of IBX or Dess Martin oxidations, I. Well, I saw this interesting paper in Angew. Chem. this week that used IBX to do an interesting double oxidation. It is a nice approach to the saxitoxin family of natural products. I thought I would share the mechanism for your edification. We don't often think about oxidizing past the ketone stage, but under enolization conditions and with the right structural features (beta nitrogen), you can oxidize the alpha carbon.

Iwamoto, O.; Koshino, H.; Hashizume, D.; Nagasawa, K., ACIEE, Early View

Al is the MAN!

From Senator, to Vice President, to President (well, he won the vote if not the chair in the Oval Office), to Oscar Winner, to Nobel Laureate. No one can say he hasn't accomplished something.

For his efforts in raising awareness about Man's influence on global climate change, Al shares the 2007 Nobel Peace Prize with the Intergovernmental Panel on Climate Change.

The 2007 Nobel Peace Prize

Well Done, Al. I think this prize is well deserved.


Why is this on a chemistry blog? I believe chemistry will be instrumental in solving problems associated with global warming. It already is - from new energy technology to new efficient materials, chemistry leads the way.

And the winner is . . .

Gerhardt Ertl for his work understanding the phenomenon of surface catalysis. In particular hydrogenation, CO2 reduction and more.



Read more about it here: 2007 Nobel Prize in Chemistry

Tetrakis Talk

{greg the chemist dialing the phone}

{ring}

AA: "Hello, this is Gregory from Alfa Aesar Technical Assistance. May I help you?"

GTC: "Yes, Hi. We have just received our order for 2 g of palladium tetrakis triphenylphospine. The shipment we received is sealed in an ampule but has a dark green color. Can we replace it with some good catalyst?"

AA: "Well, our palladium tetrakis comes in three different colors; yellow, green and brown."

GTC: "But this should be bright yellow."

AA: "We have analyzed our product and chemically it is the same. It should work fine for you."

GTC: "Palladium Tetrakis should be bright yellow."

AA: "I can see that you don't want our product. I will issue a refund and you can send it back to us."

GTC: "Um. Great. Thank you very much."

{click}

GTC: "What the hell? Three different colors? No thanks. Why didn't we order from Strem in the first place?"

{sorry for the poor photos}

Science Research and Education to get a boost

US House Resolution 2272 will be voted on today and is expected to be passed by the senate on Friday. This is good news. This bill, called the "America COMPETES Act - Creating Opportunities to Meaningfully Promote Excellence in Technology, Education and Science" is a $40 billion three-year bill that will increase funding to the National Science Foundation. But, more importantly, it provides a big boost to an area that is sorely needed here in the US - grade school Math and Science education. I have long thought that the lack of competent people in the physical sciences stems from early on in the education system. As an educator, I find the decline of students in physical sciences alarming. The number one reason I have observed for this decline is a lack of proper preparation before college in math. Students are opting for, shall I say, more wishy-washy biotechnology majors that don't require the math. My suspicions are confirmed by a recent study showing that High School math is the one thing that best prepares students for successful college physical science courses. Another thing I like about this bill is that it requires the President to hold a summit on American math and science practices and to create a Council on Innovation and Competitiveness. If I may speak frankly, our current President has pushed scientists out of governmental advising roles in favor of incompetent buffoons who believe in magic. I am also not complaining about the $22 billion increase in NSF funding. Their grants are way to small now to support a research program.

An Alkene Zipper Reaction

Aaron over at Carbon Based Curiosities has recently posted about one of my favorite reactions, the alkene zipper reaction catalyzed by 1,3-diaminopropane and potassium hydride. Most of the time this reaction works great, but it is thermodynamic and has some problems when your alkyne is stabilized by conjugation. Anyway, an interesting paper appeared on the JACS ASAP web site last week dealing with the alkene version of a zipper reaction. It is a very nice contribution from Doug Grotjahn and co-workers from San Diego State University. It utilizes a bifunctional ruthenium catalyst to walk an alkene down the chain until it reaches an alcohol. Once an enol is generated it quickly tautomerizes to the ketone form thus providing the thermodynamic sink for the reaction to fall into. The imidazole ligand on the catalyst was crucial for success and may be involved in the isomerization. A very interesting example of this difficult to accomplish process.

Douglas B. Grotjahn, Casey R. Larsen, Jeffery L. Gustafson, Reji Nair, and Abhinandini Sharma: JACS 2007, DOI: 10.1021/ja073457i

Lila's Pasties

Taitauwai, from the Chemistry & Cooking blog, prompted me to post off topic. I guess most organic chemists like to cook, myself included. Anyway, in the comments to my last post I mentioned that I still make my Grandmother's pasty recipe and Taitauwai asked for the recipe.

If anyone has been up to copper country in the upper peninsula of Michigan, you have undoubtedly encountered pasties. These are meat and potato pies that originated in England. During the early 20th century the Keewenau Peninsula was the world's richest source of copper and immigrants from Finland and England mined the ore. The pasty became a staple food for the miners. My grandfather was a copper miner and my grandmother Lila would make these wonderful treats for him to eat at work. The miners loved them because they could hold them in their hands to eat. This is as close to my grandmother's recipe as I can get, although I suspect she used shortening or lard in the crust instead of butter. I prefer them slathered with ketchup.


Ingredients
Serves 8

The Crust
3.5 cups flour
1.5 cups cold butter
1 tsp salt
~0.5 cups ice water

The Filling
2 lb ground chuck or other ground beef
4-5 medium potatoes
4-5 large carrots
1 medium rutabaga
1 large onion
salt and pepper to taste

Method
preheat ove to 375°F

The Crust
Mix the flour and salt. Cut in the butter (I use a food processor pulsing for about 10 seconds) to make a mixture the consistency of lumpy gravel. Add water by the teaspoon and toss just until the dough can be formed into a ball. Wrap with plastic wrap and refrigerate for at least 3o minutes. I like to divide the dough into four balls and slightly flatten them when I refrigerate. This dough should make 8 good sized pasties.

The Pasties
Dice or shred all the vegetables and mix with the meat. Season to taste. Divide the dough into eight and roll them out one at a time into a round oblong shape. Place a mound of the filling on half of the dough and fold over, sealing the edges with a little bit of water and pinche them together. I like to twist and fold the edges up to make the edge a bit more decorative. Place on an ungreased baking sheet and bake for 50-60 minutes, until the crust is nicely browned. Serve with ketchup or butter.

Summertime Light

I'm back after a bit of an absence. Summer has been very busy and I did take a little time to head back to my home state of Michigan for some camping. One thing I rediscovered was the joy of fireflies. We don't have them where I live now, but I remember the lazy late summer days of my youth chasing and catching these wonderful creatures. They are out in force this year glittering and lighting up the summer nights. Of course this leads to chemistry and not just nostalgic blatherings. As a kid I was fascinated by how the light was produced and we owe it all to a little molecule called Luciferin. In the presence of Luciferase and ATP, an AMP-modified luciferin is produced. This, in turn, reacts with oxygen to produce oxyluciferin in the excited state. Relaxation to the ground state produces the all too familiar orange-yellow glow of the firefly. Nature comes up with some unique ways for males to attract mates, and this is one of the more interesting ones.

ASAP Friday

A couple of ASAP articles from JACS stood out for me this morning.

The first is an interesting Nazarov cyclization followed by a Wagner-Meerwein rearrangement reported by Alison Frontier. Depending on the substitution, the path of the Nazarov is altered and the reaction is terminated by either a hydride shift or an aryl shift. Interesting paper well worth reading the details.

Jie Huang and Alison J. Frontier, JACS DOI: 10.1021/ja0716148

Mukund Sibi reported a novel organocatalytic method for the conjugate addition of hydroxylamines. The catalyst provides for both hydrogen bonding activation of the substrate and hydrogen bond-directivity for the incoming nucleophile.

Mukund P. Sibi and Kennosuke Itoh, JACS DOI: 10.1021/ja071739c

I have returned

I have returned to the US after spending a little more than two weeks in France. I enjoyed food, wine and chemistry during my visit. I was very fortunate to taste some excellent wine including the bottle you see to the right! It was amazing. Was it worth the price? Well, in my opinion, no wine is worth that much, but it truly was exceptional. I am now playing catch up with all the work that was left undone here.

I suppose on a chemistry blog, I should post some chemistry. Among the plethora of fine literature contributions I missed while I was gone was this interesting organocatalytic cascade reaction reported by List.

Jian Zhou and Benjamin List JACS ASAP. DOI: 10.1021/ja072134j

Chimie

Please pardon my lack of posts. I'm traveling in France for a couple of weeks and haven't had a chance to write anything. I visited l'École Nationale Supérieure today. I was able to see original research samples from Louis Pasteur. What a treat!

Odeur d'Asperge

Yes, it is asparagus season. I love this vegetable. Raw straight out of the garden, steamed with white wine and garlic, coated with olive oil and roasted on the grill, I can't get enough of it! Of course, for some of us that means plenty of malodorous urinary discharge. Yes, I'm talking about the infamous Asparagus Pee! The culprit - Asparagusic Acid. Derived from valine, this acid is unique to asparagus and appears to be the metabolic precursor to a number of odiferous sulfur-containing compounds. In its pure form, this colorless solid melts around 76 °C. For those with the enzyme to break it down (~40% of the population) the results appear in the urine usually within 15 minutes of ingestion. Interestingly, not everyone has the ability to smell the satisfying stench, thus complicating studies to determine why some have smelly piss and others do not. I am one of the lucky ones who can both produce copious quantities of metabolites such as methyl thioacrylate (among others) and delight in its pleasing perfume. For those of you deprived of this evolutionary gift, I have sympathy, as you will never truly enjoy the full experience of asparagus season. (edited 5/8/07, 5:28 pm to fix structures)

Your Road to a PhD

I'd like to call out some of the lurkers who read my blog to come forward and make some comments. I'm curious to find out what influences a student's decision for choice of graduate school in chemistry. So, if you have your PhD, are in a PhD program now, or going to join a PhD program soon, please tell me what was important for your choice of school. Was it location? Science? Stipend? What? Did family issues change your decision? Would you only look at schools on the coasts, or did you look across the middle of the country too? How influential were your undergraduate mentors? What about international studies? This would apply to those from the US going abroad as well as those from outside the US coming to America. And finally, what sources did you use to find graduate programs? Do you put any stock in the web sites that list rankings of graduate programs?

A Rhodium Thing

Ever since my first encounter with aldehyde C-H insertion by rhodium, I have been intrigued by the possibilities of the acylorganometallic intermediates. In Org. Lett. a nice formal [4+2] cycloaddition appeared utilizing ortho-vinyl benazaldehydes and olefins or alkynes. The reaction proceeds via C-H insertion to form an acylrhodium followed by a migratory insertion to produce a rhodacylopentene. This reacts with an alkene to form the product shown. Chiral ferrocenyl phosphine ligands afforded at least modest level of enationselectivity. If alkynes were utilized, napthol products were produced. Although most yields and selectivities were modest, it is an interesting transformation. It seems to be limited in scope. Without the arene ring cyclization did not take place. Instead the acylrhodium simply reacts with the olefin in a reductive Heck-type process to afford an acyclic ketone.

Ken Tanaka, Daiki Hojo, Takeaki Shoji, Yuji Hagiwara, and Masao Hirano, DOI: 10.1021/ol0704587

Cross Coupling of Anilines

A fascinating paper appeared on the JACS ASAP site this morning from Ueno, Chatani and Kakiuchi. They used a ruthenium catalyst to carry out a cross coupling of an aryl amine with a phenyl boronate. What is remarkable is the fact that the transition metal did oxidative addition to an aryl-nitrogen bond. Success of the reaction was dependent on having a chelating carbonyl group adjacent to the amine, however, this is still the first example of oxidative addition to a hitherto unreactive C-N bond.

Satoshi Ueno, Naoto Chatani, and Fumitoshi Kakiuchi, DOI: 10.1021/ja0713431

ASAP Thursday

Some good papers have shown up on ASAP this week. Here's two that rose to the top for me.

First is a contribution from Shu Kobayashi with some very interesting chemistry using chiral Calcium complexes. The reaction he investigated was the Michael addition of glycine derivatives with acrylates. He showed the importance of an enolizable proton on the bis-oxazoline ligand and suggests that the reactive species is a calcium Brønsted base. This generates a chiral calcium enolate that undergoes Michael addition to the acceptor. Subsequently, an intramolecular Mannich reaction ensues to afford pyrrolidines in very high selectivity.

Susumu Saito, Tetsu Tsubogo, and Shu Kobayahsi, JACS, DOI: 10.1021/ja0709730

Organocatalysis is all the rage now, and even we are trying our hand at some. Xiao has just reported a slightly new twist on organocatalysis by carrying out an intramolecular Friedel-Crafts reaction with indoles to form tricyclic compounds. Selectivities are are pretty good in some cases.

Chang-Feng Li, Hiu Liu, Jie Liao, Yi-Ju Cao, Xiao-Peng Liu, and Wen-Jing Xiao, OL, DOI: 10.1021/ol0703130

Beta Amino Acid Rearrangement

Here's the answer to the mechanism question I posed at the end of the last post. Some have suggested a 4-membered ring intermediate. While that cannot be ruled out, a mechanism that does not include the high strain of a bridged 4-membered ring seems more plausible.

Since this is an aminoacid, it will exist in it's zwitterionic form. Thus, the quaternary ammonium will not be acylated. The carboxylate is converted to a mixed anhydride. Then it undergoes a beta-elimination of the ammonium to open the 6-membered ring. This is followed by an acylation of the resulting amine to form the rearranged lactam.

This reaction was reported by Henry Rapoport (JACS 1970, 92, 5781). He cites an older paper by Ferles (Coll. Czech. Chem. Commun., 1964, 29, 2323.

Update: As liquidcarbon points out in the comments, the free amine of the ring-opened intermediate above would likely be acetylated in refluxing acetic anhydride. Another possible route to the product would involve an intramolecular acylation forming a bridging 4-membered ring, followed by beta elimination. Possible, but I'm not sure how well the bridgehead hydrogen sigma orbital would overlap with the sigma star orbital of the C-N bond.

Mechanism Challenge Answered

Tynchtyk, over at Chemist in a Transition State, posted a very interesting transformation and challenged us to propose a mechanism. Here is the reaction.

At first glance, this looks like some kind of reductive amination reaction. However, on closer inspection, you can see that there is one less carbon in the product than the starting material. Furthermore, there are no reducing agents present, only acid (and presumably water). Of course the obvious starting point is to react the secondary amine with the aldehyde to form a cyclic imminium structure. Once generated, this is nicely set up to undergo a [3,3]-sigmatropic rearrangement to transfer an allyl group to the imminium carbon. The resulting formaldehyde imminium product is then hydrolyzed in the presence of water to afford the product plus an equivalent of formaldehyde. The full mechanism is shown below. Notice I am a stickler for showing every proton transfer step! No shortcuts here.

Tynchtyk says this problem appeared in a science olypiad for High School Students in Moscow. I wish our high school education here in the states was up to this kind of challenge.

Thanks, Tynchtyk, nice problem! In the spirit of problem solving, let me pose a new challenge. This is one of my favorite transformations.

Feline Frolics

I have two cats and they drive me absolutely nuts. Always demanding and always getting in trouble. Today was no different. I had need of some thyme for my spice cupboard, so I snuck out at lunch and stopped by my favorite health food store that has a huge array of dried herbs and spices in bulk. I bought an ounce of thyme and some other goodies and stopped off at home to put them away. No sooner did I drop the bag on the kitchen floor and head to the 'little chemists room' did my biggest pain in the ass, Sam, discover a new toy. Yes, a small little plastic bag of thyme. By the time I got back to the kitchen, he had ripped the bag open and was squirming around on the floor in a big mess of herbs! *sigh* You'd think it was catnip or something, the way he was carrying on. Out of curiosity, I dug up information on the compound found in catnip. It turns out to be nepetalactone. Nothing I could find indicated that thyme contains this terpene. So what was Sam all worked up about? Well, the major volatile constituent of thyme is the terpene thymol. Very different structure than nepetalactone. Although thyme does not contain nepetalactone, catnip does contain significant amounds of thymol. Interestingly, thymol is also used as in ingredient to repel feral cats. Sam sure is odd.

ASAP Thursday

The first thing I do when I get into the lab in the morning is make my coffee. The second thing is to see what has appeared on the web journals. I suppose since I'm blogging that I should share with you the articles that catch my eye. Here's a couple from today.

Karl Scheidt has a very nice example of umpolung chemistry catalyzed by N-heterocyclic carbenes in a [3+3] cycloaddition. This appeared on the web yesterday.

Audrey Chan and Karl A. Scheidt, JACS DOI: 10.1021/ja0709167


Interestingly, I was just teaching my synthesis students about the utility of diazo compounds for cyclopropanation and Wolff rearrangements and what appears on OL this morning? A very nice and practical method for the preparation of diazo compounds. This could come in handy.

Muhammad I. Javed and Matthias Brewer, OL DOI: 10.1021/ol070515w

YACB - Yet Another Chem Blog

I need to do a blog like I need another hole in my head. Does the world really need another chemistry blog? Probably not. So, why am I doing this? I have no idea. I guess because it's fun? There's so much science out there that seems very impersonal. Perhaps blogging about chemistry allows us to inject our personal views and commentary on current chemistry. My hope is that this blog allows me to present what I find interesting in the world of Organic Chemistry and hopefully inspires people to pursue this wonderful scientific discipline.