Invisibly Important

Who does more important work: The scene-stealing front man, or the patient show-runner backstage?

Sumac in Fall, 2014

Writing at the New York Times "Motherlode" blog, author David Zweig posits that, in an era of attention-grabbing occupations - Internet whiz-kids, Wall Street financiers, American Idols - the real winners may be those who select the quiet, thoughtful "enabler" roles behind the scenes. He claims that, though they may not get the glory, such "Invisibles" end up better paid and more highly satisfied with their chosen stations.

Though Zweig volunteers occupations like structural engineers or quantitative analysts, I'd offer that most important roles in scientific research belong equally on his list: Spectroscopists. Molecular modelers. Patent examiners. Grant writers. Purification staff. Procurement. Health and Safety. Administrative assistants. Graduate students.

If you get a chance today, think about the Invisibles that help your science to succeed.
And buy that mass-spec guy a beer, already!

A Cage-y Déjà Vu

I love finding molecular "diamonds in the rough." Especially when they look, well, a bit like diamonds.

While strolling through the literature, I did a double-take at this polycyclic caged structure reported by Santiago Vázquez  (Universitat de Barcelona) and coworkers. Wow!

Source: ACIEE 2014, Vasquez et. al.

Spawned from a "highly pyramidalized" (nonplanar) olefin dimerization, it features three cyclobutanes, four "envelope" cyclopentanes, and four cyclohexanes locked in their "boat" conformations (Even worse? All those eclipsing methyl groups on each end . . .jeepers). One might expect a thing like that to fall apart in a minute with a little heat, but, amazingly, the compound remains stable up to 500 degrees Celsius.

Model of the "highly-pyramidalized" olefin monomer.
Phil Baran used to say that you could judge the strain based
on how badly your model's bonds bent...

A little reference digging proved that similar caged olefins were first produced almost half a century ago at Smith Kline & French, using a seven-step prep reliant on chloroketals and long-duration sulfuric acid stirs (yuck). A major step forward came in 1970, when Avila and Silva (San Fernando Valley State U) realized that blasting UV light at a double-Diels Alder adduct of acetylene dicarboxylic acid led to a symmetric anhydride precursor.

Vázquez extended this little gem of a starting material towards finding active antiviral analogues of amantadine. Using the imide version of Silva's anhydride, Vázquez produced a caged secondary amine (see right) that exhibits activity against mutant versions of the H1N1 flu virus. His compound also inhibits the influenza A wild-type proton channel; molecular dynamics simulations indicate that it performs a "flip" relative to bound amantadine that plugs up this pore more effectively.

Let's just hope that these new polycycles get an easier-to-pronounce nickname. 
Octopane? Rocketane? Congestane? I'm open to suggestions!