Sunday, August 3, 2014

C'mon, Let's Twist Again, Like We Did (This) Summer

Dirk Trauner: natural products chemist, vision researcher, neuropharmacologist,
. . . carbon nano-tube enthusiast?

Apparently, it's "crazy saturated hydrocarbons" month here at JLC. An astute observer clued me in to the Trauner group's latest pursuit - polytwistane. Studied for five decades by organic chemistry pioneers such as Whitlock, Deslongchamps, Oka, and von Rague Schleyer, twistanes have been tricky to coax into existence, owing to their propensity to rearrange into more stable adamantane.

In a 'gedanken' (thought) experiment, Allen, Schreiner, and Trauner mentally "add" bridging ethane units to twistane, stretching it out into a pseudo-helical oligomer (Chem. Eur. J.):

Chem. Eur. J. 2014, 1638.

Some fascinating molecular motifs fall out of their modeling studies. For example, unlike adamantane, polytwistane has three distinctly different C-C bond lengths, a factor chalked up to strain energy. However, it's in no danger of falling apart - the researchers calculate a "very modest" strain energy (~1.6 kcal / mol CH). All the hydrogens occupy positions on the outside (convex) surface of the tube. Finally, note that polytwistane is formally a polymerized version of acetylene, which we'll come back to later.

Emboldened by these in silico  results, Trauner and team take to synthesizing a basic unit of polytwistane, so-called "tritwistane" (Org. Biomol. Chem.). Starting from laticyclic polyenes -- think bicyclo[2.2.2]octene, connected end-to-end -- the researchers try a variety of electrophilic conditions to form the bond in question. Eventually, a combination of bromination / radical reduction produces the simple tritwistane oligomer:
Org. Biomol. Chem., 2014, 108.

At the close of this paper, Trauner deadpans that "attempts to synthesize polytwistane . . .from acetylene itself are ongoing in our laboratory..." Sounds like a tough nut to crack, but if he succeeds, he and his collaborators will have access to a rather rigid, narrow, twisted new material certain to possess interesting properties.

----
*Don't know the song in the title? Say hello to Chubby Checker!

Help Wanted: "Working Hours" Survey

Ofer Kedem, a postdoctoral researcher in the Weiss lab at Northwestern, has posted a survey to try and get a handle on the daily grind for academic chemists. He and his colleagues hope to garner enough data to publish their results in an open-source journal.


In the interest of statistical significance, won't you help them out?

(Thanks!)

Remember When?

Remember how we used to generate research reports?
"The scientist in a pharmaceutical company prepares his compound documents, using a variety of text and graphics systems, in a laborious cut-and-paste procedure, and transmits a hard copy to a records center, where photocopies and microforms are made and indexing takes place. When the end-user wants to retrieve his report, he asks an intermediary to do a search. The result will be a report number or access address. The hard-copy report then has to be manually retrieved, perhaps copied or printed, and delivered by mailman to the end-user. . . it is also evident that research end-users are not accessing full-text online databases to any large extent."

It's truly amazing how quickly technology has accelerated online publication in the intervening two decades.

Public library lintel, USA
Update (Aug 3) - Derek Lowe weighs in:

Friday, August 1, 2014

Honoring Carlos Barbas

Carlos F. Barbas III, a synthetic chemistry professor at Scripps, passed away just over a month ago. I remember first reading about his proline-catalyzed aldol reactions early in my graduate career; I assumed he'd one day share a Nobel Prize for organocatalysis.

In Angewandte Chemie, Phil Baran eulogizes Prof. Barbas well. I hadn't known, for example, that he had earned almost 60 patents (!), had founded three companies (Prolifaron, CovX, Zyngenia), and had mentored hundreds of students, all before the age of 50. Unbelievable.

To close, I'll use Prof. Baran's words:
"He had so much to live for and lived life to the fullest when he could.  
He would want all of you to do the same."

Tuesday, July 29, 2014

Takei's Target Audience

George Takei, an American actor / activist perhaps most famous as "Sulu" from Star Trek, inadvertently let slip a fantastic bit of advice to Terry Gross on Fresh Air (emphasis mine):

Takei: outreach specialist, helmsman
"I've been on speaking tours advocating for equality for the LGBT community. But what we noticed was I was already talking to the converted — either LGBT people or allies — and what we needed to do was reach what I maintain is the decent, fair-minded, vast middle — people who are busy pursuing their lives and don't stop to think about other issues."


Just replace "equality for the LGBT community" with "chemistry for the general public," and you stumble on a very familiar problem in the blogosphere; communication to that "vast middle" is something we ponder every day.

Monday, July 28, 2014

Cubanes! Get Your Cubanes, Here!

A cube of med-chem cubanes**
It's not often you see drug candidates advanced with cubane substructures.* A collaborative group from the UK branch of AstraZeneca and Oxford University aims to change that: a report in Organic Letters indicates they've produced gram-scale quantities of cubane derivatives with common med-chem handles already "baked in."

Starting from a 1,4-cubane diester, Burton, Davies, and Wlochal take turns elaborating each side into thiazoles, beta-diketones, nitriles, amine salts, and ynones. Though more cautious readers might expect the cubed synthons to go up in smoke, they actually seem to survive fairly rigorous conditions - boiling water, phosphoryl and oxalyl chloride, TMS triflate, LDA.

I'd be most interested to hear from any readers who integrate these new building blocks (sorry, couldn't resist!) into their research. It's hip to be...cubic.

* On Twitter, CJ (rightly) points out that the authors could have done some DSC (stability) and solubility assays, just to put minds at ease that these synthons really could be integrated into a drug campaign.

**Not a real substance (but wouldn't that be something???)

Friday, July 25, 2014

So, what's new?

A few days ago, one of my coworkers at the new job asked me to tell them what the newest, coolest trends in synthetic organic chemistry were. And, I readily confessed, even though I write this blog, I'm still in the dark about exactly what folks find exciting, even week to week!

New ligands for palladium? Been there.

Protecting group-free synthesis? Done that.

SF5? CF3? Polyfluorination? Old news, now.

Even cobalt, which seems to be the new darling of the catalysis community, feels like it's taking a comfy chair in all my favorite journals.

So, tell me, Internet: What's the newest, coolest stuff you've heard about?