Merck bails on natural products
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Every few years, you hear talk of a renaissance in natural products-based drug discovery. Well, this news should postpone the next round of optimism for a bit longer: Merck is cutting their natural products program entirely. They've had a long history in that area, but no more. That C&E News item includes an interesting detail:
"The company disclosed that it would also be closing its 50-year-old natural products drug discovery operation based in Madrid after a Merck executive inadvertently included the plan in a PowerPoint presentation to an audience that included Merck employees."
Smooth move. I'm sure some interesting ...
Source: In the Pipeline - May 8, 2008 Category: Chemists Tags: Drug Industry History Source Type: blogs
Triacetin (always liquid, always semi-edible)
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Triacetin is the glycerol triester of acetic acid: Read the rest of this post... | Read the comments on this post... (Source: Molecule of the Day)
Source: Molecule of the Day - May 7, 2008 Category: Chemists Tags: Food Source Type: blogs
Science by country
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Update: here's the map that I was imagining, thanks to Andy in the comments section. It's on the Worldmapper site linked to below, but I missed it while putting the post together. Most of my speculations turned out to be reasonable, although Venezuela (for one) looks a bit better than I thought it would, and Iran looks a bit worse. Africa and the Islamic world are, as hypothesized, almost invisible.
I’d like to see a map of the world with country size dependent on the number of scientific publications and patents – perhaps you’d want to use publications per capita, or per educated capita. That's a cartogram, and alt...
Source: In the Pipeline - May 7, 2008 Category: Chemists Tags: General Scientific News Source Type: blogs
Highlights of research that i missed while bitching about other shit
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This isn’t C&E news concentrates, but I want to cram a few in that I missed over the last few months. I’ve read and loved and you’ll love these advances in the field of chemistry:
First: DOI: 10.1126/science.1152692. Fucking brilliant piece from the Baker lab representing state of the art fuckability of proteins. The title: “De Novo Computational Design of Retro-Aldol Enzymes” gives you a half assed idea of what’s actually going on. Where the typical “state of the art” to select for proteins that do specific chemistry is to essentially make a fuck-ton of proteins and run ...
Source: The Chem Blog - May 7, 2008 Category: Chemists Authors: Kyle Finchsigmate Tags: Organic Chemistry Source Type: blogs
Mplcs for the people pt 2
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I had to take a break from writing the supporting info for a paper I’m doing. Multi colored NMRs and J values and ChemDraw and various other spectra are driving me batshit crazy. Here is a quick post to answer some common questions about the MPLC:
Q: How many grams can you load?
A: As many as you wish. It becomes cumbersome above 10 grams and hardly worth it below 40 mg. I’ve run as little as 10 mg, however, and gotten pretty good separation.
Q: Can you do gradients?
A: Yes. As stated, the gradients are fully adjustable since it’s very, very ghetto. You have two bottles and one is pulling solvent out of ...
Source: The Chem Blog - May 6, 2008 Category: Chemists Authors: Kyle Finchsigmate Tags: Organic Chemistry Source Type: blogs
Alzheimer's: a report from the front
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Several recent papers in Neurology offer some interesting ideas on Alzheimer's disease. The one that's getting some headlines today suggests that long-term use of ibuprofen has a protective effect against the disease. Actually, the authors looked at all sorts of non-steroidal antiinflammatory drugs, but the correlation was strongest for ibuprofen. (That may be just because it's used so much, however, and not some intrinsic property of that specific drug). Interestingly, although some NSAIDs have been shown to inhibit formation of beta-amyloid (the protein fragment implicated for many years in Alzheimer's), no particular ef...
Source: In the Pipeline - May 6, 2008 Category: Chemists Tags: Alzheimer ' s Disease Source Type: blogs
Fmoc (amino acid condoms)
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Automated solid-phase synthesis of biomolecules defines 20th century biology. I previously covered a protecting group that is ubiquitous in DNA synthesis, but the Nobel was actually awarded for peptide chemistry. Read the rest of this post... | Read the comments on this post... (Source: Molecule of the Day)
Source: Molecule of the Day - May 5, 2008 Category: Chemists Tags: Synthesis Source Type: blogs
Naming of names
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We order chemicals from all sorts of suppliers – big, reputable outfits like Sigma-Aldrich-Fluka all the way down to places that none of us even have heard of before. In those latter cases, the primary question is always whether or not the reagent will actually show up, and the secondary one is how long it’ll take. There are some of those small suppliers who pad their catalog with things that aren’t exactly available, not yet – but hey, they will be if someone orders them. They’ll just tell you it’s back-ordered, and tell someone in the lab to get cracking.
And when you get your compound in, they arrive in var...
Source: In the Pipeline - May 5, 2008 Category: Chemists Tags: Life in the Drug Labs Source Type: blogs
"not useful" means "not approvable", right?
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One recent drug industry setback I haven't noted around here - well, OK, to be more specific, it's a Merck setback, and boy must they be getting sick of those - is the FDA's "not approvable" letter for the Singulair/Claritin combination pill.
As the folks at the InVivoBlog note, it sure was hard, from one perspective, to see that one coming. After all, Claritin (loratadine) has an exemplary safety record and has been on the market for many years now, and Singulair (montelukast) has been selling in the billions of dollars as a stand-alone drug. No doubt many people have taken, and are taking, the two as separate pills. So ...
Source: In the Pipeline - May 2, 2008 Category: Chemists Tags: Drug Development Source Type: blogs
Dichloromethane (now healthier with 50% less chlorine!)
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Chlorinated solvents are great solvents. The polarizability of chlorine, moderate electronegativity, moderate volatility, lack of acidic protons or reactivity - it all adds up to a great reaction medium. However, they usually are toxic. Read the rest of this post... | Read the comments on this post... (Source: Molecule of the Day)
Source: Molecule of the Day - May 1, 2008 Category: Chemists Tags: Synthesis Source Type: blogs
Mplcs for the people
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I don’t like to run columns and I generally don’t. My syntheses are so bad assed, I generally work harder at figuring out purification methods that don’t require silica because columns are very, very wasteful and it hurts the earth and Al Gore’s feewings. That being said, most of my shit is purified on a column. But I’m both smart and lazy so I’ve used technology to make my life 900% easier by running flash chromatography once a month. My other column is a ghetto MPLC and I LOVE IT OMG LOL!!!!1!1one!.
An MPLC is the “medium pressure” variant of an HPLC, but they really couldn...
Source: The Chem Blog - May 1, 2008 Category: Chemists Authors: Kyle Finchsigmate Tags: In teh lab Instrumetnal Organic Chemistry Source Type: blogs
O pioneers!
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Drug Discovery Today has the first part of an article on the history of the molecular modeling field, this one covering about 1960 to 1990. It’s a for-the-record document, since as time goes on it’ll be increasingly hard to unscramble all the early approaches and players. I think this is true for almost any technology; the early years are tangled indeed.
As you would imagine, the work from the 1960s and 1970s has an otherwordly feel to it, considering the hardware that was available. And that brings up another thing common to the early years of new technologies: when you look back on them from their later years, you w...
Source: In the Pipeline - May 1, 2008 Category: Chemists Tags: In Silico Source Type: blogs
How not to do it: diazomethane
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This post will have one of those stories that I can’t vouch for personally, and I’m very glad of that. It involves making diazomethane, which will have already gotten the attention of the chemists in the crowd.
Diazomethane’s a very useful reagent, but it has to be treated the right way. You can’t buy it – no one will ship the stuff – so you have to make it fresh. (There are several such reagents). For many years there have been chemicals in the catalogs whose only real use has been to generate diazomethane when needed. Generally this involves treating some nasty N-nitroso compound with base in ether, then dis...
Source: In the Pipeline - April 30, 2008 Category: Chemists Tags: How Not to Do It Source Type: blogs
Cordaptive q and a
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So why is Merck's stock dropping - again?
The FDA just unexpectedly handed them a "not approvable" letter for their latest drug, Cordaptive. Actually, we should stop calling it that, since they also told the company that they're not going to approve that name, either. What Merck's going to do with all their promotional freebies now, I can't imagine.
What's Cordaptive, or whatever it's called, anyway?
That's Merck's newest cardiovascular drug - although the active ingredient isn't new. It's niacin, also known as vitamin B3. It's been known for many years that niacin can both lower LDL cholesterol and raise HDL, as well as ...
Source: In the Pipeline - April 29, 2008 Category: Chemists Tags: Cardiovascular Disease Source Type: blogs
Niacin (nicotine vitamins?)
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Niacin is also known as Vitamin B3. Interestingly, it's also called "nicotinic acid," and the similarity of the name to "nicotine" isn't coincidental: Read the rest of this post... | Read the comments on this post... (Source: Molecule of the Day)
Source: Molecule of the Day - April 28, 2008 Category: Chemists Tags: Medicine Source Type: blogs
A salute
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Dr. Warfield Teague is retiring this year, which makes me feel old. He was one of the professors who helped make me what I am today – in his case, partly by keeping me out of his chosen field of inorganic chemistry. It was a good move on his part; I’d surely have blown something up good and thoroughly when I got to grad school, such are the opportunities in that area.
Unfortunately for both him and for me, his Advanced Inorganic course ended up scheduled for 7:40 AM back in early 1983. I started out my college career with a barrage of classes at that hour, and made every one of them. My sophomore year, I only skipped ...
Source: In the Pipeline - April 28, 2008 Category: Chemists Tags: Inorganic Chemistry Source Type: blogs
There is clearly a wall between us
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I don’t want anyone taking the impression that I, Kyle muthafuckin Finchsigmate, am in any way disparaging those who do natural product total synthesis. You may have gotten that since sometimes people read comments and attribute them to the post author and, well, it confuses some people even more. I am not opposed to TS research. But… there are two generalizations about TS that I want to expel. Firstly, structural conformation is necessary by total synthesis and drug targets are often inspired by the complex structures of mother nature. You’ve got to do one to get the other. Secondly, it’...
Source: The Chem Blog - April 27, 2008 Category: Chemists Authors: Kyle Finchsigmate Tags: In teh lab Organic Chemistry Sciency politics Source Type: blogs
Why buy, anyway?
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I don’t want to say that this is a trend, but I notice that GSK is saying that they’re going to leave Sirtris more or less alone as well (as Takeda has said they’ll do with Millennium). The researchers in both shops should feel good about that, and not only because they’ll be keeping their jobs. They’re getting a vote of confidence in the most meaningful way that a large company can give that to its employees: by paying you money and not messing with you.
Of course, these deals have two sides to them. I don’t know what it’s like in Takeda back in Japan – my contacts inside the Japanese pharmaceutical indus...
Source: In the Pipeline - April 25, 2008 Category: Chemists Tags: Business and Markets Source Type: blogs
$720 million worth of sirtuin research
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Well, I’m back from a brief vacation, and catching up with the news. It looks like the big headline is GlaxoSmithKline’s offer for Sirtris: $720 million, which is a hefty premium (84%!) to what the company was trading for previously. Reckless waste of money, or canny deal?
I lean toward the latter, but I’ve long had a place in my heart for sirtuin research and its potential. It’s still a long shot, but it’s one of the most intriguing ones in the history of medicine. Actually, from one perspective, you wonder how long a shot it is: a biochemical pathway that seems to extend healthy life in yeast, roundworms, flie...
Source: In the Pipeline - April 24, 2008 Category: Chemists Tags: Business and Markets Source Type: blogs
Isotopic food (why was i not informed?)
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Is paying $5/liter for Fiji water not cutting it? Trying to come up with a more environmentally abhorrent, gauche hydration accessory? How would you feel about $1,000/liter, along with some iffy health benefits? Read the rest of this post... | Read the comments on this post... (Source: Molecule of the Day)
Source: Molecule of the Day - April 24, 2008 Category: Chemists Tags: Medicine Source Type: blogs
Why does cyanide pretend to be a weak field ligand in [cr(cn)5]3−?
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Lord and Baik* Generally speaking, it is difficult to study Cr chemistry because many Cr complexes are paramagnetic. Computational modeling is also not easy due to spin contamination issues. This paper by Lord and Baik provides a rationale for the observation of (NEt4)3[Cr(CN)5] in a high-spin (S = 2) ground state, suggesting that one must consider both ligand−ligand electrostatic interactions and classical ligand−field arguments in order to have a full picture of spin-state energetic ordering in a transition metal complex. What they found here was that the Coulombic repulsion between the anionic cyanide ligands domina...
Source: Organometallic Current - April 23, 2008 Category: Chemists Source Type: blogs
Big pharma’s big problem
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A while back I was lucky enough to be accidentally selected to take a big shot from big pharma out to lunch while she was visiting. I say accidentally, because I’ve been a very vocal critic of big pharma’s business model, going so far as to actually do a seminar on the subject the first year I was in graduate school (kids, don’t do that.) My position isn’t that Big Pharma is evil and they’re out to get you, it’s that they’re big, stupid useless machines that pump out gobs of fluorinated shit for metabolic syndrome and boners and buy up little companies before their quarterly report...
Source: The Chem Blog - April 22, 2008 Category: Chemists Authors: Kyle Finchsigmate Tags: Drugs! Organic Chemistry Sciency politics Source Type: blogs
Quick note
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Just wanted to let everyone know that there probably won't be a post for Monday - I'm doing some traveling, and will have irregular access to the internet. No doubt huge stories will break during the day, while I'm unable to comment on them! At any rate, we'll see if I can get something up for Tuesday. See you then! (Source: In the Pipeline)
Source: In the Pipeline - April 20, 2008 Category: Chemists Tags: Blog Housekeeping Source Type: blogs
Druggies
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So, out of about 375 of you (about 25% of Nature’s respondents) about 35% say that availability not being a factor you would essentially use some form of prescription drug to give yourself an intellectual boost, which is not too far above what Nature polled for people in the age group I assume my readership is in.
I mean, possibly 10% higher, but these polls are horribly inaccurate anyway, so I’ll just call everything even and say, maybe if availability weren’t an issue, But it’s not as high as another number. Apparently, almost 60% of you have already tried a drug for recreational purposes already...
Source: The Chem Blog - April 20, 2008 Category: Chemists Authors: Kyle Finchsigmate Tags: Drugs! Sciency politics Source Type: blogs
Mercury beating heart
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Oscillating reactions are neat; I should write up one of my favorites sometime... Here, electrons flow from iron metal to mercury (I) sulfate to chromium (VI) oxide. Listen to the video for a step-by step explanation... Read the rest of this post... | Read the comments on this post... (Source: Molecule of the Day)
Source: Molecule of the Day - April 20, 2008 Category: Chemists Tags: Inorganic Source Type: blogs
Molecules in the news...
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A couple previous molecules of the day were in the news today: polylactide and lead chromate. Read the rest of this post... | Read the comments on this post... (Source: Molecule of the Day)
Source: Molecule of the Day - April 18, 2008 Category: Chemists Tags: Not Really a Molecule Source Type: blogs
Cut it out. cut it out now.
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File this under “does no one any good”. As many of you will have seen, JAMA just published a report on various studies that Merck has conducted and published over the years on Vioxx. The conclusion was that the company basically wrote the papers, and then went shopping for well-known academic names as authors. No, this one isn’t going to be good for anyone involved.
There seems little doubt that this practice does go on. I’ve never been in a position to see it happen, but it’s been reported for years. There are whole companies whose business is “scientific writing and communication”, and some of these seem t...
Source: In the Pipeline - April 18, 2008 Category: Chemists Tags: The Dark Side Source Type: blogs
Getting smarter already?
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There have been several articles in Nature recently about performance-enhancing drugs. But these aren’t steroids or blood-cell therapies: they’re performance enhancers for scientists and engineers. Chief among them are Ritalin (methylphenidate), Provigil (modafinil), and various beta-blockers, to enhance concentration and wakefulness. The whole topic came to the fore last December, in an article suggestively titled "Professor's Little Helper". Here are the results of their informal readership poll. It's not a huge trend, at least not yet. The fraction of their self-selected sample who had never taken any such compound ...
Source: In the Pipeline - April 17, 2008 Category: Chemists Tags: General Scientific News Source Type: blogs
Fun with bacteria
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A recent interview in Nature Reviews Drug Discovery with John Powers, formerly of the FDA, points out some problems in designing antibacterial drug trials. Some of these are unique to this area, although others we're stuck with wherever we go.
For one thing, it’s surprisingly hard to make sure, when you’re selecting patients, that the people you’re letting into the trial have the disease that you’re trying to treat. The example used is that some 5% of the patients who present with cough actually have pneumonia. Pneumonia is a very good disease to treat with antibacterial drugs, but you’d better make sure that yo...
Source: In the Pipeline - April 16, 2008 Category: Chemists Tags: Infectious Diseases Source Type: blogs
Nickel-catalyzed decarbonylative addition of phthalimides to alkynes
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Kajita, Matsubara,* and Kurahashi*This is an interesting reaction to make isoquinolones. Their design was quite logical and it did work at the first try, although the yield of the desired product was only 18%. The authors managed to improve the yield by the introduction of electron withdrawing Ar groups. The mechanism was proposed to proceed by a nucleophilic attack of Ni(0) to the amide moiety (an oxidative addition of C-N to Ni) followed by decarbonylation, insertion of the alkyne to the phenyl C-Ni bond, and finally reductive elimination of the product to regenerate the Ni(0) catalyst. The fate of CO was not mentioned, ...
Source: Organometallic Current - April 16, 2008 Category: Chemists Source Type: blogs
Phytic acid (think unositol? think again...)
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Phytic acid is an inositol derivative: Read the rest of this post... | Read the comments on this post... (Source: Molecule of the Day)
Source: Molecule of the Day - April 16, 2008 Category: Chemists Tags: Food Source Type: blogs
Inositol (weird carbs)
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Inositol is a sugar: Read the rest of this post... | Read the comments on this post... (Source: Molecule of the Day)
Source: Molecule of the Day - April 15, 2008 Category: Chemists Tags: Food Source Type: blogs
Walk around some
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Not many chemists come into the drug industry knowing very much about biology. I certainly didn’t, not on the level that was needed. It’s not surprising, but it’s also not as much of a handicap as you’d think, at least not at first.
That’s because the first job of a new hire in the med-chem department is to crank out compounds, and that goes for both the PhD and Master’s levels. (Those roles diverge as time goes on, though). But with a few obvious rules in hand (no hot reactive functional groups, no huge greasy monster molecules, etc.), a person can contribute reasonable-looking compounds pretty quickly. No bi...
Source: In the Pipeline - April 15, 2008 Category: Chemists Tags: How To Get a Pharma Job Source Type: blogs
Shall we have some drugs?
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By now, everyone has heard about scientists using drugs to become smarter, better, faster like the Kanye West. For those under rocks, 20% of “scientists” have admitted to using performance enhancing drugs (a.k.a. Nootropics)- drugs which I’ve actually blogged about like Modafinil and other’s I have yet touched, like Ritalin.
The 1 in 5 number is a bit surprising, but it brought up a number of well written and freely accessible deliberations on the use of such drugs here. (Note the persistence of the age old practice of addressing letters to the editor as SIR. I demand righteous indignation be heape...
Source: The Chem Blog - April 15, 2008 Category: Chemists Authors: Kyle Finchsigmate Tags: Drugs! Sciency politics Source Type: blogs
Fifteen minutes shot
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If today's post didn't waste enough of your time, here's another way to carve something out of the economy: name all the elements, in any order but correctly spelled, in fifteen minutes.
I scored a 97 - forgot some of the more recently-named transition metals, and I didn't even bother with the placeholder names for 112 and up. Enjoy - and if you score higher than I did, don't forget to note that fact in the comments. Not that I have to tell anyone. . . (Source: In the Pipeline)
Source: In the Pipeline - April 14, 2008 Category: Chemists Source Type: blogs
A meditation on solvents
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Hexane (or its cheaper, less well-defined cousin, petroleum ether) is the proto-solvent. Light and thin, it’s the weakest at actually dissolving anything, so it’s the background to most stronger mixtures in a purification. Like most other solvents, though, it’ll strip the oils right off your skin, leaving you spiderwebbed with white lines across your fingers and in need of some lotion. Its smell isn’t pleasant, but it doesn’t really stink, either. A nonchemist would easily place it in the oil / kerosene / gasoline end of things, which is exactly where it belongs.
When I first encountered ethyl acetate back in co...
Source: In the Pipeline - April 14, 2008 Category: Chemists Tags: Life in the Drug Labs Source Type: blogs
Make some oseltamivir with bmt
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The Bird Flu is a ravaging disease that could kill quadrillions of people and is thus of paramount importance when an Angew. Chem. publication (DOI: 10.1002/anie.200800282) is on the line. Fortunately, before the disease can star pillaging and burninating, it can be stopped (STOPPED I TELL YOU!) by Roche’s Oseltamivir. The problem, as we all know, is that Oseltamivir’s starting material is synthesized from nothing less than the tongue of Caucasian baby fetuses (or Chinese Star anise) and it’s already simplistic biosynthesis in the bacterium who shall not be named is not to be discussed.
Very good. Now tha...
Source: The Chem Blog - April 13, 2008 Category: Chemists Authors: Kyle Finchsigmate Tags: In teh lab Organic Chemistry Source Type: blogs
Free sushi in the cafeteria!
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So Takeda has surprised the folks at Millennium with a buyout offer. (They're battening down the hatches over in Japan, and looking for something new). I know several people over at the latter company, and I can imagine that yesterday was one of the less productive days around the labs. No doubt there was a lot of initial fear that this would be a Pfizer-style deal (see below), but as the day went on that didn’t seem to be the case. I’m told that retention bonuses are being offered, along with several other features to try to keep the Millennium operation running.
Takeda’s been increasing its US presence over the ye...
Source: In the Pipeline - April 11, 2008 Category: Chemists Tags: Business and Markets Source Type: blogs
Tellurium (it only gets worse as you keep going down)
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As you go down the group, the smells only get worse. You don't smell oxygen (you're soaking in it), sulfur compounds tend to be pretty stinky, selenium compounds are pretty rank, and purportedly, tellurium compounds are the worst. Read the rest of this post... | Read the comments on this post... (Source: Molecule of the Day)
Source: Molecule of the Day - April 10, 2008 Category: Chemists Tags: Stinky Source Type: blogs
Exubera, safety, and no guarantees
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As mentioned yesterday, I would have to say that Mannkind is in big trouble. I’d never heard of the company until the Wonder Drug Factory was closing back in Connecticut, but Mannkind was moving some of their operations into the state around then and interviewed a number of my former colleagues.
The whole inhaled-insulin idea had already taken some pretty severe blows. The massive failure of Exubera was the biggest, although a creative person could always argue that a better product with a more convenient delivery system could succeed in its place. But then Novo Nordisk and Eli Lilly (serious diabetes players, both of t...
Source: In the Pipeline - April 10, 2008 Category: Chemists Tags: Diabetes and Obesity Source Type: blogs
Selenocysteine (#21)
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As far as I know, selenocysteine is the only reason you need selenium in your diet (which you almost certainly get enough of; the requirement is vanishingly small, (Source: Molecule of the Day)
Source: Molecule of the Day - April 10, 2008 Category: Chemists Tags: Stinky Source Type: blogs
Essential references and texts of an organic synthetic chemist
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I recently did a rather modest web design job for my boss and he has promised a rather modest reward in return -specifically a chemistry and/or drug design book. I have, I think, a few books which I consider to be absolute essentials to the organic chemist, though they are only a few. He’s give me a soft limit of about $150 but I’m sure he’d go higher. I’ve listed here books that everyone (IMHO) should own if they want to seriously consider themselves synthetic chemists (and/or organic chemists). So, I need book suggestions which are obviously not listed here. (You should buy these books if you don&...
Source: The Chem Blog - April 9, 2008 Category: Chemists Authors: Kyle Finchsigmate Tags: In teh lab Organic Chemistry Uncategorized Source Type: blogs
And you thought exubera was a disaster before
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I don't usually do more than one post a day, but this really caught my eye. In an ongoing review of Pfizer's (now discontinued) inhaled insulin (Exubera), an increased chance of lung cancer has turned up among participants in the clinical trials. Six of the over four thousand patients in the trials on Exubera have since developed the disease, versus one of the similarly-sized control group. Six isn't many, but with that large a sample size, it's something that statistically can't be ignored, either.
The concerns would have to be, naturally, that this number could increase, since damage to lung tissue might take a while to...
Source: In the Pipeline - April 9, 2008 Category: Chemists Tags: Diabetes and Obesity Source Type: blogs
Another pop quiz!
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Time for another quick quiz on whether you have what it takes to be a big-time medicinal chemist. Prepare for some not-so-welcome old friends to visit you yet again:
1. Your two main assays refuse to act as if they’re part of the same project. Most of your potent compounds in the first enzyme assay don’t do much against the cells, and the best cellular compounds are no great shakes in the enzyme assay. There’s a narrow zone of overlap, but it doesn’t look big or robust enough to base the whole project on. Do you pursue the cellular activity, on the theory that that’s the effect you’re looking for, or pursue th...
Source: In the Pipeline - April 9, 2008 Category: Chemists Tags: Life in the Drug Labs Source Type: blogs
Fun with tunichromes
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Ever hear of tunicates? They’re these little sea squirt creatures that sit around day and night, filtering sea water for food. The weird thing about them is that although they have blood, it isn’t red, but in many species a Mr. Spock shade of bluish green. That’s because they don’t concentrate iron there, but rather vanadium, in the same row of the periodic table.
You don’t hear much about vanadium. Not even chemists hear all that much about it, at least not since the 1980s heyday of one of the Sharpless epoxidation reactions that uses it as a catalyst. (An old colleague of mine, Carsten Bolm, has been doing hi...
Source: In the Pipeline - April 8, 2008 Category: Chemists Tags: Things I ' m Glad I Don t Do Source Type: blogs
How chemistry saved my collard greens
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I was wondering around my local grocer a few weeks ago when I decided to give something new a try. I wanted to make some Collard greens. So, like an old pro, I bellied up to the “greens” section of the supermarket and grabbed a few bunches of them. While I was carefully inspecting my Collards, a black lady appeared beside me, grinning, and abruptly asked, “What are you gunna do with those things?” My knee jerk reaction was to placater her with Caucasian platitudes about how I intended to chop them into an endive and radicchio salad topped with Duck Confit, but I don’t think that quickly. Inste...
Source: The Chem Blog - April 7, 2008 Category: Chemists Authors: Kyle Finchsigmate Tags: Uncategorized Source Type: blogs
Pre-emption for real?
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There's talk again about an idea that's been kicking around for some years: are drug companies shielded from liability after the FDA has approved their drugs for sale?
Obviously, the current answer is "Not at all": consider the lawsuits over Vioxx. But the decision by the Supreme Court in February in Riegel v. Medtronic has the idea being taken seriously again. That ruling seems to shield medical device companies from lawsuits over safety or efficacy after the FDA has signed off on those issues - as long as the device is the same, and used in the approved manner. And no, for the politically motivated among the readership,...
Source: In the Pipeline - April 7, 2008 Category: Chemists Tags: Drug Development Source Type: blogs
Anhydrous cerium(iii) chloride + libr solution in thf
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LiBr 24.5g (282 mmol) was dried in a 0.5L RB flask on highvac (0.2 Torr) at 150C for 12h (overnight), then cooled under Ar to RT and anh THF 0.25L was added via cannula. The the mixture was stirred under Ar until complete dissolution (20 min).
Meanwhile, powdered CeCl3.7H2O 47.5g (Aldrich; 127.5 mmol) was combined with re-distilled thionyl chloride 175mL (2.4 mol) in a 0.5L flask equipped with a reflux condenser topped with a gas outlet tube (vented into a large Erlenmeyer flask filled with soda lime pellets). The mixture was placed on a 70C bath and stirred vigorously for 2 hours; at the end of this period the gas...
Source: Org Prep Daily - April 5, 2008 Category: Chemists Authors: milkshake Tags: procedures Source Type: blogs
Another cholesterol medication goes down (or does it)?
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This is turning into Cardiovascular Week around the blog, I have to say, and not in a good way. The latest news is the failure of a drug candidate from Takeda, TAK-475 (lapaquistat). They were in the lead in the field of squalene synthase inhibitors for cholesterol lowering (many other companies have taken a crack at this target, and dropped out along the way)., and their compound once had hopes of being a pretty big deal.
Not any more. In retrospect, the bell sounded late last year, when the company had to stop dosing at their highest level. Elevated transaminase levels were being seen in the treatment groups as the dos...
Source: In the Pipeline - April 4, 2008 Category: Chemists Tags: Cardiovascular Disease Source Type: blogs
Idiot proof dendrimer synthesis
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Dendrimers are the new black. They’ll come with your next iPod and you’ll see Madonna flying into Chemistry labs to illegally adopt them. But they suffer from a rather attractive flaw: they’re a bitch to make.
Any reaction where you can plan a whole vacation around is GREAT. The traditional synthesis (or at least the best and highest yielding procedure I could find) for PAMAM dendrimers involves a wonderfully uncomplicated 7 day room temperature stir after you just did a 3 day reaction. Seriously, you can make all your vacations working vacations with this sort of chemistry. Karl Sharples’s came alo...
Source: The Chem Blog - April 4, 2008 Category: Chemists Authors: Kyle Finchsigmate Tags: Nanothingiees Organic Chemistry Source Type: blogs
