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!

Curious Collaborations

Tried telecommuting? It's tough when you're bench-bound, since you can't really catalyze by cell phone, or take HPLC by HTTP. Of course, research takes strange twists and turns all the time: witness the schism between compound "designers" and "makers" in Pfizer's geographically divided new organization. 

Long-distance scientific collaboration crops up in all sorts of interesting places. Creative minds always find a way, albeit leaning heavily on technology to help smooth things out. Here's a few interesting examples:

Physics by Ham Radio (1950) - While on sabbatical in Brazil, Richard Feynman continued his Caltech research by hooking up with a pirate ham radio operator.

"I found an amateur radio operator in Brazil, [but] because there was something slightly illegal about it, he'd give me some call letters...So I'd say 'This is WKWX. Could you please tell me the spacing between the certain levels in boron we talked about last week?"

Source:Brian Dettmer, 2008
Thanks to Chemjobber for pointing this out!

Manuscript Writing by Phone, Post, and Boat (1969) -  Writing in How the Hippies Saved Physics (p. 47), author David Kaiser describes how two authors - Abner Shimony and John Clauser - tackled paper submissions from afar. While writing their first quantum mechanics manuscript, Clauser decided to sail down the East coast, towards an eventual postdoc at Berkeley. Here's how it went:

" ...each time Clauser sailed into a port along the East Coast, he would find a telephone and check in with Shimony...then Shimony would mail copies of the edited draft to every marina in the next city on Clauser's itinerary, 'some of which I picked up,' Clauser explained, "and some of which are probably still waiting there for all I know.'"

SPARC (1992) - The Space Physics and Aeronomy Research Collaboratory, first established at the University of Michigan, grew over the next 6 years to include several worldwide radio telescopes. The project now incorporates behavioral scientists, computer programmers, physicists, and astronomers, who "...sit down to their computers in the comfort of their offices and call up a screen that allows them to control and gather data from more than a dozen instruments located around--and above--the globe." Online collaborative tools developed by this consortium include Java programs, chat rooms, and a digital whiteboard.


Instant Messaging, Liveblogging, Wikis (mid-2000s) - Regular readers recall the recent uptick in live-blogging, that is, conducting a live experiment while posting data, observations, and commentary. Paul at Tot Syn famously debunked NaH oxidation, and Azmanam proved that LemiShine cleaner contains citric acid. The open science movement brings together scientists from around the globe to live-edit papers on electronic documents called wikis. My biggest surprise? Digging up an IEEE abstract on eChemIM. Apparently, it's a real-time application that allows exchange of structures and protein sequences through a simple pop-up window. Sounds like a cool new way to collaborate!


Readers, have I left out your favorite way to connect? Let me know in the comments.