Update

Contrary to popular opinion, I’m alive, well and trying to get established in a new part of the country.  Please sit tight.

A Brief History Lesson

I recently Googled the name “John Roberts.”  It turns out that the search ended up being a bit too broad.  Apart from websites concerning the Chief Justice of the US Supreme Court, a New York-based comic and a collection of spas operating in Ohio, the name John Roberts has seemingly little to do with chemistry (at least in the public eye).  Dig a bit deeper, and you’ll find information about a John D. Roberts of Caltech fame.

I draw attention to Roberts because of his recently published JOC perspective—a brief autobiography spanning the development of organic chemistry over the past 70 years (J. Org. Chem. 2009, 74, 4897-4917).  Being a true lover of historical perspective, I found Roberts’ essay to be informative about how research was conducted years ago.  Sure, we can read about secondhand accounts of “old school” organic chemistry in textbooks, but there’s really no substitute for vivid, subjective stories from primary sources. 

What really jumped out at me (in the article) was the breadth of background Roberts gained before really delving into true organic chemistry.  I think this is a trait we (as organic chemists) can relate to; our lives don’t just revolve around carbon-carbon bond formation or chemoselectivity.  We supplement our training with spectroscopy, biochemistry, quantitative analysis, metals, quantum mechanics, history and/or business. 

In other news, I’ve been busy finishing up last minute experiments before departing my research lab for a completely new part of the country and employment that doesn’t involve lab glasses or dressing like a graduate student (I’m deciding if I want to blog about that at a later point).  I realized earlier today that by social standards I’m officially beyond ABD.  All I have to do is walk.

My tasks as of late have involved synthesizing metal-hydride complexes, teaching undergraduate laboratories, advising undergraduate researchers and wrestling with a damn sulfonamide that doesn’t want to go into solution very well (though, I think as of this weekend, I’ve officially tamed the beast). 

Headed back into the lab.  Wish me luck.

Intellectual Property Forum

Please spread the word:

If you have nothing to do in the late summer months, there's always Beijing.  The second annual Internatioinal Pharmaceutical and Chemical Intellectual Property Forum will be taking place in Beijing, China (August 5-8, 2009).  

ACS Chemistry and the Law members (Division website) can register for a significantly discounted price.

For more information, please visit the Forum website (www.chinaipforum.net).

Bees

While replacing the specialty gas line in my hood, my brand new undergrad made an discovery in the cap.  I’ve posted the photographic evidence below (a data collection courtesy of my new BlackBerry).  My undergrad (let’s call him “Mr. Smith”) claimed that he didn’t want to be working in the lab and get stung (an outlier scenario, I know).  We sent the cap back with our good friends from Airgas.  

Utility in the Strecker Reaction

Today, over breakfast, I decided to peruse the literature (courtesy of ChemFeeds).

One paper that really jumped out at me was Grygorenko’s synthesis of conformationally restricted amino acids (CRAAs; link to ASAP).  I thought that this paper was interesting for various reasons.  Although I won’t attempt to dissect the purpose (the authors claim that these molecules are “very important to drug design”; to each his or her own), I will raise a red flag at the graphical abstract (which I reproduced in ChemDraw).  From an organic chemist’s perspective, ask yourself “what’s wrong with these molecules.”  I’m surprised a referee didn’t pick up the mistake.

Chemical semantics aside, the authors contend that commonly employed chiral routes involve disconnection at the C-N bond in the 2-azabicyclo[3.1.1]heptane-1-carboxylic acid.  Thus in these strategies, the bicyclic[3.1.1] framework derives from the corresponding n-halocyclobutane amino acid through a 6-exo-tet cyclization. 

I was fascinated by the authors use of the Strecker reaction to prepare these compounds.  Adolph Strecker purportedly reported the first instance of what is now called the “Strecker” reaction.  The reaction involves the treatment of a carbonyl with an amine in the presence of a cyanide anion to create an a-amino acid via formation of an aminonitrile.  Hydrolysis of the nitrile moiety results in the formation of the carboxylate. 

From an electron pushing perspective, the Strecker reaction is a somewhat complex transformation involving lots of minor, simple details.  In Grygorenko’s synthesis, benzylamine mediates the initial deprotonation of the cyanohydrin thus generating the cyanide anion and acetone.  Keep in mind that the ammonium will likely be at equilibrium with HCN formation given their relative pKa values. 

Acid-catalyzed iminium formation is performed by the benzyl amine.  The resultant positive charge is quenched through nucleophilic attack of the cyanide anion, thus resulting in formation of the secondary benzyl amine.  Finally, 6-exo-tet cyclization results in the formation of the bicyclic nitrile.  Acid-catalyzed hydrolysis converts the nitrile into the corresponding carboxylate (not shown, dig out your sophomore organic textbook). 

P.S. I apologise for the length of time between posts.  Long story short, I successfully defended my Ph.D. research ~2 weeks ago and have been finalizing the assembly of my dissertation (a.k.a. making edits and formatting).  I'm working on a post that covers the lessons learned from this journey...stay tuned ;-)

New Email System

My University just made a monumental change over the weekend in abandoning their email system for a partnership with Google’s Gmail.  Instead of the miserly 10 MB of email space we were given from day one of grad school, we’re now allowed 7 GB, a significant increase over the previous technology (implemented in 2003).  Unfortuanately, Mac Mail does not want to play nice with the new server, and I can’t download cached emails to my laptop.  As such, I have to manually pull up a server, sign into the University’s student service-type program and then click a link just to pull up my email, all which could be avoided by using Mac Mail.

Well…let me back up.  It’s not the Mac (or PC’s for that matter) that’s the problem.  It is a fact that the University’s IT department hasn’t developed specific instructions on now to sync their student’s Gmail accounts with programs such as Mac Mail or Outlook.  This normally wouldn’t be an issue if my email account were, “MrPerfect221@gmail.com,” for example.  However, with the change in email came new email addresses that look something like, “MrPerfect221@descriptor.university.com.”  So, as I configure my email account on my Mac, it’s not clear if you refer to the SMTP server (in one case) as “gmail.com” or “descriptor.university.com” or some combination of the two or a 4^th-20^th option that no one knows about (tends to happen more often than not). 

Now, combine all of this silliness with my role as an organic chemist and, hopefully, you’ll see the issue unfold.  All NMR spectra are immediately forwarded to our University email account.  Having “tighter” access to my email now means that my precious data is stored somewhere on this vast planet of ours in a Gmail server instead of in the appendix of my dissertation (where it needs to be). 

I’ve also been trading emails with my future employer about the giant packet of info that was sent a few days ago.  It’s a pain to stop everything I’m doing every few hours, pull up a browser, sign in and make a few mouse clicks to access my mail, when I could be doing it using my email software.  I guess I’m just disappointed that the process isn’t streamlined.

Does anyone have any suggestions?

Re-issuing Good Chemistry

I recently bought a 2009 re-issued copy of Pearl Jam’s first album “Ten,” originally released back in 1991.  Those who know me well are also aware of my interest in Pearl Jam; I enjoy collecting demos or live versions of their music.  Anyhow, their officially released re-issue contains a remixed version of their 1991 album and (in my opinion) parts of it sound distinctly different than the original mix.  For you music buffs out there in internet land, Brendan O’Brien—the original producer—dumped the supplemental reverb applied to the original tracks in this newer version.  As a result, the guitars and drums sound much cleaner and less wet (I recommend listening to both versions of “Why Go” or “Oceans” for a good example of the remixing).

Thinking about the whole concept of “re-issue” got me thinking about organic chemistry (big surprise).  How often do scientists report fantastically optimized results, table the idea, and then revisit it at a later date (to make vast improvements)?  Or better yet, how much “new” chemistry has derived from “re-issuing” processed developed in the late 19^th or early 20^th century?  My PI calls refers to this particular phenomenon as, “teaching an old dog new tricks.”  In writing my dissertation (an ongoing process) I had the pleasure of reading Lipshutz’s recent review about cuprate chemistry (Synlett 2009, 509-524; DOI: 10.1055/s-0028-1087923).  This personalized narrative discusses the Lipshutz group efforts and contributions to the field of copper(I) hydride chemistry. 

This article is of particular interest apart from discussing it at length in the ‘ol thesis.  A few months back, I had a conversation with a colleague of mine who claimed that since Stryker’s contributions, “conjugate reduction chemistry has (basically) fallen to the wayside.”  I recall laughing out loud at his remark.  “What about Lipshutz or Riant or even Buchwald,” I asked.  He claimed, with a sense of arrogance, that their work was “just a new twist on Stryker’s original work.”  Based off of this logic, if someone successfully synthesized Taxol from table sugar in three steps, would it be considered a new twist on Nicolau or Holton’s contributions?  Arrogance aside, this idea of “re-issuing” is a common phenomenon in research chemistry.  It’s done frequently, often to the tune of 10-20 additional printed publications (apart from the seminal contribution).  Perhaps, it’s these instances that call into question the process of “re-issuing” chemistry. 

That said, re-issued chemistry can result in significantly new discoveries and improvements on original methods.  Taking the conjugate reduction example, Stryker’s catalytic reactions, performed under a high pressure of H₂, were plagued with over-reduced products.  In switching the stoichiometric hydride source from hydrogen gas to PMHS, Lipshutz reported a vast improvement in reaction times and overall yields (Tetrahedron 2000, 56, 2779-2788; doi: 10.1016/S0040-4020(00)00132-0).  This change has spawned a whole new area of carbon-carbon bond formation, particularly in the field of reductive alkylation reactions. 

While I’m genuinely interested in the idea of inventing new and exciting reactions, the thought of tweaked processes resulting in “re-issued” chemistry is largely appealing (when done responsibly).  A prominent neutron chemist once told me that real chemistry lies in unexplored places.  “We want to be doing things that others aren’t,” he said.  I agree.  But on occasion, it’s necessary to explore the landscapes previously claimed by others for the betterment of the (scientific) community as a whole.