Tuesday, May 19, 2015

Buried Treasure

Regular readers know that I've been collecting names of chemistry faculty moves for a while now. I had to chuckle at this particular announcement, by friend of the blog (and fellow Tweeter) Prof. Karl Gademann. From two clicks deep on his group's home page:
"Prof. Gademann's first professorial appointment was at the EPFL in Lausanne, and he currently holds a chair at the University of Basel as a full professor. He has been elected to the board of the Swiss Academy of Sciences, and is affiliated to the National Centres of Competence in Research ‘Chemical Biology’ and ‘Molecular Systems Engineering’. Karl Gademann will move in Summer 2015 to the University of Zürich. His work has been recognized by a number of international awards, including the Latsis prize, the Novartis Early Career Award, the Ruzicka Medal, The Liebig Lecture by the German Chemical Society, and the European Young Investigator Award."
Thanks to an eagle-eyed commenter for the link.

Also, from both sites (UZH, BAS), it would appear that Dr. Gademann looks most professional when posed behind a rotovap condenser.

Best of luck in the new position, Karl - we'll add you to the list!

Monday, May 4, 2015

Interlude

It's so refreshing that Spring has finally sprung in Big City, USA.





This one was snapped by an observant reader whilst on a
hunt for a new couch. Cost of each? $30.

Brewing Up Shikimic Acid

Could preparing Tamiflu starters be as simple as making your morning cappuccino?

The lab instrument in question,
straight from the Supporting Info
(I <3 pictures in SI)
Jason Smith and coworkers from the University of Tasmania have reported a PHWE - pressurized hot water extraction - to obtain shikimic acid, a common starting material in several routes to oseltamivir phosphate (Tamiflu). In a preparation that begs repetition, they grind up up 20 g of Chinese star anise, mix with sand, and quickly wash with a hot ethanol-water mixture using a household espresso maker (see right).

The researchers claim that, after a quick silica plug, they obtain 5.5% (w/w) of "sufficiently pure"* shikimic acid. I'd encourage you to go see the NMR spectra for yourself.

Of course, pressing common kitchen tools into synthetic service isn't news. My undergraduate lab group ordered many of its smaller-bore funnels and spatulae from a kitchen supply store. And let's not forget grindstone chemistry, popularized by the late Ajay Bose at the Stevens Institute of Technology, which used a stainless-steel blender** to combine solid reagents into heterocycles.

If molecular gastronomy involves bringing the techniques of organic and biochemistry into the kitchen, perhaps this represents its antipode, some sort of 'reverse' molecular gastronomy in which kitchen appliances and techniques inform bench science. Makes perfect sense; after all (say it with me)...Chemistry is Just Like Cooking!

--
*Based on the 1H NMR, I'm guessing their material hovers around 90% pure. Still good, given a 2-minute prep time. 
**Kitchen-Aid, no less - high-quality 'instruments' for high-quality chemistry : )

Wanted: Chemistry Humorists...err, Editors

Earlier this week, I took Angewandte Chemie to task: their (in)famous graphical abstract puns just weren't funny anymore. They responded with a job opening*, potentially to write exactly those puns I had just maligned. What a coincidence!

Chemistry writers of the world: Are you witty? Good at writing? Want to live in Germany?
Link's embedded in the Tweet.

*Sorry, Chemjobber, I know this is usually your beat, but I really couldn't resist.

Thursday, April 16, 2015

Spot-Checking Antibacterials in PLoS One

Update (April 17) - Commenters here and at Derek's place have set off alarm bells to potentially doctored spectra. Stay tuned...
--

Ever looked at a molecule and thought something was just...off?

A little while ago, I browsed through the latest edition of PLoS One, the open science journal. I don't often go there for chemistry publications, but curiosity struck, so I typed, "antibacterial NMR" (I think) into the search box. Up came this paper, from 2013, announcing:
  1. A novel alkaloid, xinghaiamine A, isolated from a marine bacterium, that...
  2. Had novel structural features, such as a sulfoxide and acenaphthylene ring, rarely seen, and...
  3. That showed decent lead activity against MRSA strains (2.7-5.5 uM MIC).
First thought: "Wow!" Second thought: "If this is so great, why is it buried in PLoS One?"

Then I happened to look at the proposed structure for this potential panacea:

Jiao, Zhang, Zhao, Hu, Suh, PLoS One, 2013

[Rubs eyes in disbelief].

Sulfonylated "ladderane" substructure.
A (4,7) disubstituted acenaphthylene bridge.
A previously-unknown-to-science (and virtually unknown to SciFinder) 4-4-5-6 ring system.
Can that really be correct?

Naturally, I made a model of one "half" of the presumed dimeric molecule:

Xinghaiamine A, pseudo-axial conformation,
assumed diastereomer of the (4-4-5-6) ring system.
The red circles are supposed to be bonded together...
I've taken apart and reassembled this molecule a few times, and can't seem to access any diastereomer that 1) looks energetically minimized, and 2) can actually have the acenaphthylene bridge the way the authors specify without "strain energy" popping out the plastic bonds.

Perusing the analyticals in the Supporting Information, I'm puzzled by a few more bits:

Jiao, Zhang, Zhao, Hu, Suh, PLoS One2013

The IR, briefly addressed in the text as suggestive of "[the] presence of a sulfoxide functional group" due to the 1082 cm-1 band, but contains peaks suggestive of:
  • alcohols, primary amines: 3383 cm-1 band
  • heteroaromatics: 743, 846 cm-1 band
The published 1H NMR has no peak labeling or integration (tsk, tsk).

That the COSY shows only one set of strong H/H correlations out of the 6 posited protons on the conjugated ring, which should not fit with the proposed structure. Nor should the seeming high symmetry of the ring fit with the proposed substitution.

--
Readers, what do you make of this? What kept this out of a more mainstream chemistry journal? 
Do you agree with the assigned structure? (Am I just shouting in the wind here?)

April 17 - Uh-oh...check out these anonymous commenters' finds on Derek's blog:
Potential editing of the H/H COSY


...and the HMBC

Thanks to All My Readers and Tweeps!


Presidential Chemists

From an astute commenter in the 2015-2016 Bumper Cars post, we hear about Prof. Andrew Hamilton's appointment to serve as the next President of New York University (NYU). Congrats!

I'm sure chemblogosphere NYU alums Phil Baran and ChemBark are overjoyed.

Readers, how many chemists now serve as chancellors, provosts, or presidents at academic institutions?

Here's who I know about today - I'll add more as I hear about them in the comments.

Eva Åkesson - Uppsala University
Vicki Colvin - Brown University
David M. Dooley - University of Rhode Island
Marye Anne Fox - UC San Diego
Andrew Hamilton - New York University
Wolfgang Herrmann - TU Munich
Peter Schreiner - Justis Liebig Universitat, Giessen
John D. Simon - Lehigh University
H. Holden Thorp - Washington University in St. Louis
Mark Wrighton - Washington University in St. Louis