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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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March 23, 2009

(Don't) Trust And (Don't) Verify

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Posted by Derek

When a medicinal chemist starts digging around through the literature for help on some chemistry, there are several levels of results. The most welcome are recent papers that solve the exact problem you’re looking for, of course. We’re not in business to come up with new reactions (unless we have to,) so if someone else has done the work, that’s great.

Almost as good are similar reactions from the reliable literature. Different people have different borders drawn for that territory, but everyone would include solid publications like the Journal of Organic Chemistry, particularly if it’s a full paper. Interestingly, that’s because JOC is generally not the place (these days) for the hottest work to appear, which takes that out of the equation. As has been proven several times over the last few years, journals can stumble when they try to publish stuff that’s a bit too avant-garde: some of that work is so cutting-edge that it hasn’t even been done yet.

The communications-only journals vary widely in quality, so they’re generally a step down from the better full-paper publications. One big reason is that the communications often don’t include much in the way of full experimental details. One way to tell how useful a journal is would be to measure how surprised you are when you can’t repeat chemistry from it. If you can’t get some reaction from Tetrahedron Letters to work, you just say “Oh, well”, whereas a dud reaction from a long JOC paper gives you more of a feeling of betrayal.

Then there are patents. When I was a grad student or post-doc, I tended to just ignore patent references, but that was partly because I couldn’t get access to them very easily. Now there’s less of an excuse, and anyone who bypasses them is missing out on a lot of useful preparations. They don’t always work quite as wonderfully as advertised, but there are a lot of very interesting intermediate compounds that are described nowhere else. And when the patent goes on to prepare seventy-five enabled compounds from said intermediate, you can be reasonably sure that you’ll be able to make enough for your own needs.

But there are patents, and then there are patents. If there’s no spectroscopic data associated with a compound, you’d better step lightly. Similarly, there’s journal literature and there’s. . .well, there are an awful lot of journals out there. And some of ‘em are, in fact, awful. SciFinder and other such tools are perfectly capable of tossing out references, in the same list as everything else, to the Bulletin of Some Obscure Country’s Academy of Sciences, 1953, communicated from Unpronounceable University in Everyone Leaves Province. You’re on your own if you track these things down, and good luck to you.

In a category all its own is the Soviet-era Russian literature. There are a large number of compounds (particularly heterocycles) that are described nowhere else, and a wide range of these things are available in English translation. But (as with patents) you have to be careful. Some of this material is really worthwhile and unique, and some of it is. . .well, my theory has always been that people in the Soviet era were willing to do a lot to remain "academicians", considering what some of the other options were like. Can't say I blame them, either, but it means that the more obscure Communist-era references need to be approached cautiously. If you're depending on a reference from J. Siberian Oil Chemist's Soc., (a real journal, at one point), then you may need to start looking for some backup.

Update: On the other hand, here's a new mathematics journal that's made up, explicitly, of papers that have been rejected by peer review. Each includes a summary of why it was rejected, and why the original author thinks it's still important anyway. . .thanks to Marginal Revolution for the tip.

Comments (11) + TrackBacks (0) | Category: The Scientific Literature


1. emjeff on March 23, 2009 8:58 AM writes...

The call for papers for this esteemed journal, Rejecta Mathematica, is dated November 2007. Looks like this "experiment" did not work out...

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2. milkshake on March 23, 2009 9:30 AM writes...

the problem with soviet-era organic chemistry journals is 1) laconic procedures 2) NMRs at best continuous wave electromagnet 40 MHz. I was once excited about oligoprenoid cyclizations done by people in Moldova, and they published series of papers on their methodology up to 90s - papers that were never cited by other groups. Reproducing their procedure provided a chromatographically "pure" product that had each methyl in the proton spectra present as four signals...

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3. RB Woodweird on March 23, 2009 10:34 AM writes...

In the States, every grant application has ...and it kills cancer cells!!! appended. I imagine that in the old USSR, every grant application had ...and can be used against clusters of enemy troops in air-dispersal shells!!! tacked on.

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4. milkshake on March 23, 2009 11:00 AM writes...

there were obviously no grant applications in USSR and the organophosphate departments has a separate wing at the institutes - with a security guard and key/card access. The dudes working for military had far higher salaries and never talked about chemistry in the caffeteria. And then there were entire "closed cities" that did not exist on the maps and their residents did not get to travel too much...

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5. bitter pill on March 23, 2009 7:29 PM writes...

I have enjoyed contacting the primary author when a procedure is totally irreproducible. It is often blamed on a post-doc (or undergrad) who left early. This happened so many times in a row that a colleague observed "That post doc sure gets around".

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6. Thomas McEntee on March 24, 2009 6:38 AM writes...

Re Derek's last paragraph and Milkshake's comment (#4), a fascinating read on the Soviet/Russian CW program from the perspective of a PhD-level chemist is "State Secrets" by Vil S Mirzayanov (Outskirts Press, 2009). In the early 1990s, he blew the whistle on a new family of Soviet CW agents that fell outside the Chemical Weapons Convention and on the hypocrisy of his country. He was charged and imprisoned, but in 1994 was ultimately cleared of all charges.

It was possible for good scientists to do good work in the Soviet system but it took will, courage, persistence, a supportive network, and some degree of luck.

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7. Dave_n on March 24, 2009 6:10 PM writes...

I always remember way back in my more youthful days (middle 1960s)in the Unit of Nitrogen Fixation in the UK that we would not believe a paper by Vol'pin and Shur (excuse spelling!) on the fixation of nitrogen by a Ti complex. Fast forward about 10 years, when it was repeated in the West and did!

A very large amount of coordination chemistry with rather strange metals and also a very large amount of antibiotic discovery came out of the USSR in the 1940s-1970s and in retrospect a large proportion was right.

Might be worth rechecking some of those papers in Doklady Nauk even today. Dave_n

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8. InfMP on March 24, 2009 8:47 PM writes...

I usually find the potential energy barrier that needs to be crossed to get an article that isn`t online is too high. I think maybe it is because I came into the chemistry world in 2005, but I can`t even find the patience to walk 5 min to the library, spend 15 min trying to find the damn bookshelf and photocopy it.

I have never heard of any of my group members going to the library, but I found all the old advertisments (not online), really amusing. OH MAN 60 MHZ????? what? totally amazing!
Mind you, I wish chemicals were still that cheap.

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9. baby bird on March 25, 2009 4:41 AM writes...

I have a problem with newish papers claiming wonderful perfect gazillion megahertz NMR and then describing the product as a brown or worse the ubiquitous 'yellow oil' sets off my BS detector immediately.
give me a nice looking material with melting points etc and just 60MHz NMR over dirty coloured oils and suspicious 400Mhz NMR any day.

we need a 'journal of irreproduceable results' where people can post literature procedures that didn't exactly work as described, or were down right lies.

none of the current journal publishers are going to run with this one they are fat and happy publishing more and more marginal stuff in more and more focussed journals and pretending that the signal to noise is worth charging extortionate amounts for access.

All journals seem now have more unrepeatable nonsense now than before and peer review appears to involve an old boys network. the reviewers don't have the time to check stuff and so tend to go with on the reputation of the submitter.
watch out for any procedure in any journal or patent from any Japanese pharma company, they it would appear, are more slippery than most:

I can think of a particular example where 880 aqueous ammonia was used in a nucleophilic substitution and where it was sealed and heated to 160oC in a pressure vessel yet the pressure reported was only 1.4 barg...the autogenous pressure due to the water alone would be way more than that. this synthetic procedure has been supposedly repeated several times, nobody has pointed out the bullshit, which makes me think that people are copying and pasting references. this procedure also forms part of a patent...
obviously they have special ammonia.

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10. zts on March 25, 2009 6:19 AM writes...

Baby Bird said, "I have a problem with newish papers claiming wonderful perfect gazillion megahertz NMR and then describing the product as a brown or worse the ubiquitous 'yellow oil' sets off my BS detector immediately."

Depending on what you made these compounds for, these colored products are very often clean enough. The amount of colored impurity it takes to impart a color to something can be incredibly small. If my compounds are analytically pure but are yellow, or even brown, is that really that bad? Sometimes, try as you might, you'll never get rid of the color. If it was a colorless impurity, you'd never even know about it. Sure, there are situations where trace impurities are important, but for total synthesis or medicinal chemistry, I think >95% clean is just fine.

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11. milkshake on March 30, 2009 5:58 AM writes...

Maybe in the future, the articles published in journals online will have a moderated comment section.

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