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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: derekb.lowe@gmail.com Twitter: Dereklowe

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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

« More On Reproducing Scientific Results: Organic Chemistry Edition | Main | Just How Do Enzymes Work? »

August 16, 2012

Shootmenowicene

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Posted by Derek

After mentioning the natural product Shootmenowicene yesterday, I note that See Arr Oh is reporting that the total synthesis of this compound is now down to only 47 steps. I think the purity could be improved with a prep GC of one of the early intermediates (or perhaps a spinning band distillation), but that's about all his synthesis is missing. . .

Comments (31) + TrackBacks (0) | Category: Chemical News


COMMENTS

1. MLBpitcher and Medicinal Chemist on August 16, 2012 8:13 AM writes...

How's the Yankees Derek? It must suck to be released by the Indians, but you're still making $15 million a year.

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2. Surviving Synthesizer on August 16, 2012 8:33 AM writes...

Oh Man! Now the designers are going to want me to make 10 mg for testing against the kinase of the month! By the end of the week!

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3. David Formerly Known as a Chemist on August 16, 2012 8:35 AM writes...

Prep GC, spinning band distillation...don't forget to throw in a good old prep Chromatotron purification step! Gotta love making those plates.

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4. Helical_Investor on August 16, 2012 8:50 AM writes...

I understand the material is not consistent with the natural product according to the circular dichroism. Perhaps the material needs to be synthesized in the Southern hemisphere.

Zz

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5. drug_hunter on August 16, 2012 8:56 AM writes...

@2, "surviving synthesizer" - The tribunal has noted with displeasure your failure to capitalize the "D" in "Designers." This is a very serious breach of protocol. You have been warned.

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6. okemist on August 16, 2012 9:05 AM writes...

shootmenowicene-rotflmao. the funniest chemistry stuff on the web, thanks Derek. go yanks!

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7. MTK on August 16, 2012 9:09 AM writes...

@3,

I used to love the chromatotron and I was an absolute pro at making those plates. Had it down I tell you.

No cracks, no bubbles, no piles of silica sliding around back and forth at the bottom of the chromatotron if the silica slid off the plate.

Money, everytime.

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8. John Wayne on August 16, 2012 10:08 AM writes...

Wow, and I thought I was one of the only people who even knew what a chromatotron was. I must not be the only old chemist who figured out this newfangled 'internet' thingy.

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9. Chemjobber on August 16, 2012 10:25 AM writes...

I'm not an old chemist (right? right?), but we used a Chromatotron in both my undergraduate and graduate labs (less so in my graduate labs.) I graduated undergraduate at the turn of the century (love saying that!)

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10. Anonymous on August 16, 2012 10:29 AM writes...

I brought this to the attention of a couple of famous chemists I know. One said that they isolated and characterized this compound first, many years ago, but chose not to publish because it was only one member (and the least complex member, they added) of the family of shootmenowicenes. They are looking for the old notebooks as I write this.

Another one told me that they synthesized shootmenowicene by a 12-step route but chose not to publish because it was a racemic synthesis and it was their intention to follow-up with the enantiospecific synthesis in due course. They are looking for the old NMR spectra but aren't sure which box they're in.

Finally, I give much credit to See Arr Oh on a job well done. I hope there will be a poster or seminar at the ACS meeting in Philly. Which Section / Session / Cocktail Reception?

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11. Anonymous on August 16, 2012 10:37 AM writes...

Hmm, maybe GSK will buy it now.

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12. I Miss the 90s on August 16, 2012 10:39 AM writes...

Our group is working on scaling this compound up for advanced studies, but we are having problems with our Argonaut Quest 210, and the red button on the side of my Flash 75 won't pop out when I pressurize the system. WTF!

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13. See Arr Oh on August 16, 2012 10:46 AM writes...

Thanks for the kind comments, but we're not out of the woods yet. After differentiating the individual diastereomers by their induced chiral NMR fields, we'll proceed to separate them, which I'm told works best as the per-ruthenate salt.

Any of you a formulations person? We're getting about 5 different polymorphs of Shootmenowicene A...

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14. Derek Lowe on August 16, 2012 11:02 AM writes...

Oh, I really enjoyed my Chromatotron. I even made up a silver-nitrate impregnated rotor plate to separate a couple of alkene isomers. That must mean that I was pretty hard core even (or especially) back in 1985!

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15. David Formerly Known as a Chemist on August 16, 2012 1:04 PM writes...

I hated making those Chromatotron plates, but man, did I ever separate some diastereomeric bisanthracenediones! That was way back in 1988 or so, before HPLCs were very commonly seen in organic labs.

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16. JC on August 16, 2012 1:13 PM writes...

Chromatotron, leader of the Benchbots in their struggle against the Designercons.

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17. Hap on August 16, 2012 1:21 PM writes...

FVP of an early intermediate in its synthesis would help. You can do FVP on kilo scale, right? I thought you could do anything with FVP.

If you can't do that, there are microreactors for that as well. I'm sure they'll work on kilo scale, too.

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18. newnickname on August 16, 2012 1:28 PM writes...

I used a Chromatotron, too! With the quartz plate cover to follow the bands by UV!

You can still buy a Chromatotron and PRE-FAB plates from Analtech but they call it the CycloGraph. Let Ana L'Tech explain ... www.ichromatography.com /the-adventures-of-ana-ltech.html (close the space for URL).

Technically, on a theoretical level, Chromatotron has about the same max resolving power as flash. It can be more convenient than flash in some cases. When you can see your bands (color or UV), you just collect what you want; no TLCs needed.

DISCLAIMER: I am not a shill for Analtech. But I am shilling to meet Ana L'Tech!

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19. WCA on August 16, 2012 2:08 PM writes...

The key to this synthesis will be utilizing Green chemistry throughout. Water as solvent for each step is preferred.

Maybe incorporating a in-line flow system so that you can simply run the entire sequence without breaking containment.

Should be doable.

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20. David Formerly Known as a Chemist on August 16, 2012 2:26 PM writes...

Perhaps a continuous-flow microreactor constructed from nanomaterials could perform all 47 steps on a cartridge no larger than a credit card. The microreactors could be stacked (millions upon millions), producing grams per day. Oh what the hell, kilograms per day! You know that nanotech makes everything work better.

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21. KCN on August 16, 2012 2:55 PM writes...

Synthesized it enantiospecifically in one step from CO2. And professor Light will be pleased to know it cost me nothing. Trivial.
Next!

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22. Dr. La Clair on August 16, 2012 3:06 PM writes...

This has been a side project for a few months, but it's finished, and I'm working on the manuscript right now. I just a few more NMR's for the SI. Should be out next month in ACIE.

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23. Incha on August 16, 2012 4:27 PM writes...

Until this has been passed to the Journal of Reproducible chemistry, I won't believe any of it!

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24. Incha on August 16, 2012 5:53 PM writes...

Until this has been passed to the Journal of Reproducible chemistry, I won't believe any of it!

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25. Anonymous BMS Researcher on August 16, 2012 7:51 PM writes...

My wife pointed out this synthesis requires a very expensive catalyst: resublimated thiotimoline. Wasn't there a posting a while back about a company claiming to make water act like a drug by playing back electromagnetic fields from its NMR spectrum? Maybe this technology could reduce the amount of thiotimoline required.

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26. old man on August 16, 2012 9:12 PM writes...

@13, Those are not diastereomers, they are atropisomers. Get yourself a variable temperature NMR for cryin' out loud. And I always loved the screeching sound as the chromatotron plate grinding tool hits bottom. Better than fingernails on a chalk board.

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27. Scott Rychnovsky on August 16, 2012 9:47 PM writes...

JJ (@22), I'll take a look at your NMRs for you.

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28. Clinical pharmacologist on August 17, 2012 12:55 AM writes...

#25 if you are going to take your wife's approach then you are going to need a robot system to control the asymmetrical moving, isomer activity.

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29. Fred the Fourth on August 17, 2012 5:40 PM writes...

I'm beginning to think Prof. Light must be right, though not for the reasons he thinks he is.
What a load of time-wasting wild-eyed speculation!
Thiotimoline, indeed. That was discovered when, back in '48 or thereabouts? (though I have an odd feeling that even asking that particular question is begging for trouble...)

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30. Humble Scrivener (Mrs. Anonymous BMS Researcher) on August 17, 2012 5:54 PM writes...

It was ca. 1978 by the time I learned about thiotimoline in one of the Asimov vintage anthologies. Too bad its catalytic uses preclude putting it into fountain pen and inkjet cartridges to improve publication timelines.

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31. EJCorey on August 19, 2012 11:27 AM writes...

This result was critically dependent on unpublished flow chemistry research from RB Woodward for which I was the inspiration. I demand credit!

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