Corante

About this Author
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: derekb.lowe@gmail.com Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Paying People to Take Their Medications | Main | Merck Layoffs - Underway? »

June 16, 2010

Sparteine and Other Fine Chemical Shortages

Email This Entry

Posted by Derek

One of the folks over at Chemistry Blog has run into a shortage: he and his labmates have tried to order (-) sparteine from every supplier in the book, and there's none to be had. So if anyone has a big dusty bottle of it sitting around, you might drop these desperate chemists a line. But that got me thinking about the way things suddenly dry up like this.

The situation is different than for an industrial chemical shortage, like the acetonitrile crunch that we went through a while back (and which has long since eased up). It's quite unusual for a bulk chemical like that to go down; several factors hit all at once in that case, and it affected an awful lot of people who needed the solvent. But fine chemicals are much weirder. When you trace some of them back to their real sources, you sometimes find that there are really only a couple of people in the world at any given time making some of these things. Or, in many cases, you find that there's no one making it at all - someone made a bunch a few years ago for some reason, sold the excess to a supplier, and everyone else has been buying it from that same bottle ever since.

So when one of these small-scale itemsevaporates, the reason can be supply: no one makes it any more. Or it can be demand-driven: a single drug company's scale-up group can deplete the world's commercial supply of some strange little molecule when they suddenly switch to a 500-gram run. Everyone working in such a group knows to call all the suppliers when they have a prep calling for some weirdo starting material, and they'll often take the precaution of ordering whatever's out there to be had. (That serves as a cushion while they contract someone else to crank out a batch or figure out how to make it themselves). Naturally, you'd rather have your drug candidates depend only on things that can be ordered in tank car lots, but that's just not always possible.

So it could be that someone needed a lot of (-) sparteine for an asymmetric synthesis recently, and bought up the existing world stocks. But this one sounds like more of a supply problem. There would appear to be customers out there, who have been draining the existing stocks, but no one's been able to replenish them. TCI apparently stated that it's the starting material for (-) sparteine that has become unavailable, but that sounds a bit funny, since it would surprise me if the material on the market is synthetic. Sparteine is a naturally occurring alkaloid, found in several species of plant, and it's very hard to compete with isolation of the natural product in those cases.

Perhaps TCI means that the usual plant source is unavailable - that's happened before, too. A spike in Tamiflu demand a few years ago suddenly sent the price of star anise up to record levels, since the chiral starting material (shikimic acid) in the usual synthesis was most conveniently isolated from that source. But for sparteine, it looks as if the isolation comes from plants in the broom family, which are not exactly rare shrubs, so I'm not sure what's going on. Any ideas?

Comments (19) + TrackBacks (0) | Category: Chemical News | Life in the Drug Labs


COMMENTS

1. Jim on June 16, 2010 8:17 AM writes...

No idea about sparteine, but I've been having a similar problem with mercuric cyanide. Stuff is like gold dust at the moment - except that I could get gold dust from Aldrich at a moment's notice...

Permalink to Comment

2. Virgil on June 16, 2010 8:21 AM writes...

Another thing that can drive up demand for rare molecules is the publication of a paper describing a novel biological activity or use. As soon as the paper is published, everyone rushes out and orders some, to "see what it does". This can be especially bad if the molecule has only one supplier.

Permalink to Comment

3. Imants on June 16, 2010 8:27 AM writes...

This is indeed how it often is. A dozen of companies might have a compound in their catalog while the real producer is one. We recently saw this with CaS - multiple sources all of a suddenly had the same quality problem.

Permalink to Comment

4. KB on June 16, 2010 8:29 AM writes...

Ah I love these stories. It looks so simple and thus easy to make and yet it isn't. I remember when I was a PhD student that a certain research group in Oxford purchased pretty much the entire world's bulk supply of kainic acid and for years afterwards it was only ever available in 25mg pots. Probably still is.

Permalink to Comment

5. startup on June 16, 2010 8:55 AM writes...

I know! I was trying to order some a few months ago and was most displeased to find out that it was not only not available anywhere, but also that the price has tripled since our last order.

Permalink to Comment

6. A Nonny Mouse on June 16, 2010 9:27 AM writes...

Have they tried MP Bio? A reasonably obscure (to most bench chemists) supplier which claims to have it.

Reminds me of back in the early 90s when a Hungarian company decided to stop making the chiral intermediate for chloramphenicol without realising that they were essentially the only supplier. The price of chloramphenicol quadrupled in a few months..

Permalink to Comment

7. Sili on June 16, 2010 9:33 AM writes...

I wish I had the talent - business-, extraction- and synthesis-wise to benefit from knowledge like this.

I happened to visit the department with a chocolatecake last week, and ran into my old group's lab tech. She'd finally received a mere 100 g of starting material many months delayed. Supposedly they'd gone through three different preps to get even that much. Which none of us understood, since before that we have a gallon jug of the stuff standing around. It was getting depleted as I was leaving and I recall filtering off the decomposed picolinic acid and putting stuff in a smaller bottle. Seriously - it must have been full of other gunk as well by then, but worked without much issue in synthesis (well, not for me, because I'm an arse).

I instructed her to distrust any analytical data they'd sent along and get an in-house nmr before doing anything else. Also suggested she look at the two threads we had here recently and put in a review of the incompetents at http://www.molport.com/buy-chemicals/customer-reviews

I also suggested asking the assembled talents here if anyone had any suggestion, but I might as well do that, myself, since I'm whining anyway:

Who'd you recommend for making bis(2-picolyl)amine, [2-(C5H4N-CH2-]2NH ? Good ideas for synthesis would be interesting as well. I really wanted to do it through reductive amination - perhaps even catalytic, but I was too stupid/clumsy/lazy, myself.

Permalink to Comment

8. CMCguy on June 16, 2010 10:12 AM writes...

The "one global source" seems to be a common theme for many research chemicals even though found in many suppliers catalogs and can be a major headache when moving to development and scale-up. Although agree with comment "Naturally, you'd rather have your drug candidates depend only on things that can be ordered in tank car lots, but that's just not always possible" I would hope either the med chemists do consider this factor in final candidate selections and/or at least look at starting materials/intermediates that have clear chemical routes from materials that are likely to be more readily available so can be made in tank car loads. I have been involved in several projects where the lead compounds showed indistinguishable activities with no thought was given to acquisition of materials and the primary choice had the hardest supply issues. Ultimately this is solvable and usually becomes part of the process development lore yet can be significant effort required in the transition from bench to production.

Permalink to Comment

9. RM on June 16, 2010 10:34 AM writes...

Why is it that I immediately thought of Laurel and Hardy when I read the title?

"Well, that's another fine chemical shortage you've gotten me into!"

Permalink to Comment

10. JasonP on June 16, 2010 10:59 AM writes...

Hmmm....would rare fine chemical production be decent start up company material in the US you think?

Permalink to Comment

11. chiral on June 16, 2010 11:26 AM writes...

We had the same problem with sparteine availibility a few days back. An easier solution is to order sparteine pentahydrate from Acros (which is much cheaper than sparteine itself) and then extract sparteine from it. Its easy and there is a org syn prep for it. The yields can be 50-55% but its still cheaper than the actual material from aldrich.
Hope it helps to those in dire need.

Permalink to Comment

12. chiral on June 16, 2010 11:29 AM writes...

Sorry....its sparteine sulfate pentahydrate rather than sparteine pentahydrate.

Permalink to Comment

13. RandDChemist on June 16, 2010 12:42 PM writes...

At one point many years ago, the (-)-sparteine free base wasn't much more expensive than the sulfate pentahydrate. The prep is easy, and the material looks better coming from the salt. Either way, you'll want to distill it.

Aldrich is out of all forms of it. Acros says it available by request from Belgium.

Most people should know about the salt, or find out about it were they to source it well.

Permalink to Comment

14. milkshake on June 16, 2010 3:07 PM writes...

30 g of 2-cyanopyridine were dissolved in 140 mL of ethanol/water (6:1), 10% Pd on charcoal 1.6g was added, and the mixture was treated with H2 under pressure (20-30 atm) for 9 h at room temperature. The mixture was filtered, the filtrate evaporated to dryness, and the residual oil distilled batchwise in a Kugelrohr apparatus to give 15 g of di(2-picoly1)amine as a pale yellow oil, bp 130-145C at 0.1 torr [JACS 106 (1984) page 7937]

Permalink to Comment

15. Harry on June 16, 2010 7:17 PM writes...

Sili-

My company has made bis picolylamine on a kilo scale. I don't have a current price, since we sold the last we had on hand a year or so ago.

You can contact me at breamfisherman (at) yahoo (dot) com (email address I use when I may attract spam). for more information.

FYI- it's not quite as easy as milkshake's prep, there are a couple tricks.

Harry

Permalink to Comment

16. Liz on June 18, 2010 12:55 AM writes...

We had this problem with glass slide boxes. Apparently they all come from Wheaton (except for a mini size we can't use). We were told by Wheaton that they get their raw materials from one source and this source had no raw material for some reason.

Three people in the lab made orders for them, not knowing that they didn't exist, so we just got about 18 after waiting almost a year. We originally needed six.

I had no idea that they were that difficult to manufacture.

Permalink to Comment

17. toothbrush holders on April 16, 2012 8:31 AM writes...

Such a type of blog post will definitely click to numerous viewers. A good article and useful for its written content. Many thanks for sharing it up!. Thanks! Will probably be nice to anyone who usess it, including myself. Sustain the nice work for positive ill take a look at extra posts. A lot more Additional .

Permalink to Comment

18. Miguel Angel on May 11, 2012 2:17 PM writes...

hi everyone, I would like to know if anyone have found a good supplier for (-)-sparteine. I would like to make some quiral organolitiums and I really need it. I will thank any help. Miguel Angel

Permalink to Comment

19. PRI LLC on June 20, 2012 1:36 PM writes...

Sparteine

Contacts us @ sales@pharmaresourcesint.com

Permalink to Comment

POST A COMMENT




Remember Me?



EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
What If?
Novartis Impresses Where Others Have Failed
Exelixis Against the Wall
A Last Summer Day Off
The Early FDA
Drug Repurposing
The Smallest Drugs
Life Is Too Short For Some Journal Feeds