This week’s group meeting’s talk on ‘Strategies in Synthetic Planning’ raised a number of interesting points for discussion, but I wanted to put just one to my readers and the online synthetic community: what’s your favourite total synthesis?
Strangely, the question actually put to the group was a bit less subjective—the word "best" was used, as if there's a single right answer—but I've found that whenever conversations along these lines occur, that there's a wide spectrum of answers. The history of total synthesis—while rather short compared to many branches of science—is still vast, and there’s a lot of great work out there that I'm not sure can (or should) be ranked on some absolute scale. One problem is that there are just too many criteria on which syntheses can be judged (length, creativity, yield, scalability...); although I’ve heard several people liken completing a total synthesis to running a marathon, there’s much more to it than just doing it fast! I remember Rob Stockman introducing Andrew Phillips while chairing a session at a conference a few years ago by comparing the styles of different synthetic chemists to those of different painters, and I think that the analogy is a good one. Looking back across the body of work produced by the synthetic community it’s easy to identify the “old masters”, but few would be prepared to rank them in order of greatness; you’d just as well choose a "best" fruit or colour. Sure, there are now a bunch of metrics for assessing synthesis on everything from atom economy to percentage ideality, but I’m pretty sure that’s not how K. C. Nicolaou decided what to put in his Classics in Total Synthesis series and I think it’ll be a while before we see a really elegant route to a target designed by a computer.
Anyway, that’s probably enough pontification for one blog post, so here are a few of my favourite syntheses and a few that came up in recent conversations—please add yours and your thoughts in the comments!
Somewhat later than planned, I'm off to the US tomorrow to finally start my postdoc! I suspect I'm gonna be pretty busy finding a place to live and settling into my new group for the next couple of weeks, so things could be quite quiet around here for a little while. I hope to resume blogging when I've gotten into a new routine, and I'm looking forward to having lots of new experiences to write about. Thanks for your advice and patience!
P.s. Although this is a dedicated organic synthesis blog, lots of people have asked me about my move to the US, so I'll probably attempt to write a series like Nessa's Transatlantic Tales about my experiences and mix that in with the usual content when normal service resumes. What do you think?
Update 03/04/2013: Chemjobber made a few!
Thanks to a recent xkcd comic I've just discovered a wonderfully concise new way to communicate – non-overlapping Venn Diagrams:
For example, here's a statement my boss made last week expounded thus:
I quite enjoy the contradiction between the visual simplicity of displaying information in this way and the fact that it's actually a lot more effort to construct these than write a sentence that conveys the same information, as well as their highly inefficient use of space. There's just something kind of amusing about them. Or I think so, anyway.
Give it a go, and share any good (chemistry related) ones you can think of in the comments. I've just put one in a talk I'm writing on acyclic stereocontrol for a group meeting; I'll let you know how that goes down next week!
Sorry things have been so quiet around here; it's been a hectic month! Here's something silly born of an unusual conversation over coffee.
The office microwave: unnecessary chemophobia?
The Merck Index, along with Fieser and Fieser's Reagents for Organic Synthesis, Greene’s Protective Groups, March’s Advanced Organic Chemistry and Amarego’s Purification of Laboratory Chemicals is one of those books that any self-respecting organic research group will have a copy of. It’s an iconic reference work, although its usefulness has definitely waned in recent decades with the rise of the internet, Scifinder/Reaxys/Chemspider and Wikipedia. As Derek reported before Christmas, it was recently acquired by the RSC, who have just released an updated edition. I mostly use mine to pass the time waiting for NMRs to run, or when I need a more reputable reference than Wikipedia for a paper or report. However, all of that changed last week when a tea break conversation sparked a bizarre new game: The Merck Index Challenge.
Anyone who’s ever flicked through a copy will probably have noticed that amongst all the drugs, solvents, salts and plants there are a number of… aberrant… entries. For example, Whiskey. And Lard. And Raspberries. And Quorn. And Milk. Thus, the question arose: could a meal be constructed using only ingredients from the Merck Index? Better yet, could one manage three courses?
Ever see a reaction in the literature and think, "that seems a little too good to be true..."? Retro Baeyer-Villiger reaction? Quantitative cleavage of methyl ethers with Amberlyst-15? Catalytic reduction of alcohols to hydrocarbons with Dess-Martin? Bring it on! Ever struggle with a sensitive or fiddly reaction and wonder, "is it just me? Should this work?"? Well, now you don't have to! Thanks to a collaborative new website brought to you by See Arr Oh, with a little help from Organometallica, Mat Katcher and Myself. Now, if you find a reaction you can't reproduce or don't believe, simply head over to Blog Syn, and let us know. Alternatively, if you think you'd like to be part of helping to make the literature a little bit more reproducible, pay us a visit and see what needs checking! If we all just run a few extra reactions a year we should be able to save chemists around the world many wasted hours and much frustration. You might even have some fun, make some new friends, and perhaps even learn some chemistry besides!
1. Or email See Arr Oh or myself
As a synthetic chemist I'm always on the hunt for interesting molecules to disconnect/speculate about, and a couple of natural products published at the start of this month (Organic Letters ASAP; DOI: 10.1021/ol3028303) immediately caught my eye:
So far so good! Don't start looking for mistakes yet! The problems start when the authors go on to suggest what I'm going to politely call a most intriguing biosynthetic proposal:
It's not too bad at the start, borrowing heavily from Baldwin and Whitehead's hypothesis for manzamine and related alkaloids. The problems come one the authors need to go from the pyridinium dimer to the natural product itself. How the C4-C5 bond is supposed to form on the middle line is beyond me, and the arrows in the cyclopropane opening seem to go in entirely the wrong direction, but all that stuff seems entirely sensible compared to the madness on the top line. I know that people often play a bit fast and loose with steps in proposed biosyntheses; it's easy to shrug and go "there's probably an enzyme that does that", but this just shows no understanding whatsoever of arrow pushing. I can't believe this got into an ACS journal, or am I missing something?
I've got a few emails lately pointing me in the direction of good resources such as the much discussed How To Chemdraw video and the beautiful new name-reaction.com. I've also just recently become aware of great new(ish) blogs like Not The Lab, Doctor Galactic, The Chemistry Cascade, Chemistry Tips and Techniques, and The Organic Solution. However, I am sure that for every useful resource (blog, tutorial, reference...) that I've read, I've missed many more! Below are the links on my resource page at present, and you can see my blogroll on the right. I've just noticed that the former hasn't been updated in over a year. So, what should I be reading or linking to? Drop me a comment or email (N.B. new address on about page)!
Incidentally, if your bookmark/RSS feed to this site points to my old eristocracy.co.uk domain, you should change it as I'm losing that tomorrow.
Hi all, we* interrupt our* scheduled** programming to bring you an exciting** Chemistry Carnival entry! See Arr Oh recently had the brilliant idea of a Chem Coach Carnival, where people in different chemical careers describe their working lives to give others an idea of what it's like to be in their shoes. Here's my entry, which unfortunately seems to have turned out a bit too long:
What do you do?
As you might have guessed, I'm currently a 'postdoc' or post-doctoral research associate at a UK university. If you're not familiar with the academic hierarchy you can see where this fits in the academic food chain here, thanks to Karl Collins.
What does a typical day involve?
I'm one of three postdocs in a research group of around twenty people engaged in diverse projects across the spectrum of organic chemistry. When I was at school The RSC ran a campaign to tell people that 'not all chemists wear white coats', but I'm proud to do so for 90% of a normal day. At the moment I'm mostly working on a short-ish biomimetic alkaloid synthesis but in addition to my own project(s), I also get to field questions from PhD and MSci students, show people how to do stuff in the lab, write papers, work on my own crazy ideas, manage an MSci student and worry about what I'm doing with my life. I also do some teaching in the form of undergraduate tutorials, which is great fun. My job is essentially to solve an increasingly varied and intricate series of puzzles, and it's good.
How did you get where you are?
It sometimes feels like I've spent my whole life in full time education as I started university straight after school and my PhD a few months after I finished my undergrad. As it happens, I'm currently still at the same institution from which I obtained my PhD a few months back. Staying in one place like this is usually inadvisable, but it's not a bad university, there's a good climbing wall nearby, and my current position is really just a short term filler until I move to the US next year for a 'real' postdoc. Goodness knows what I'll do after that. Fortunately, thanks to the shorter British PhD, I've only just turned 26.
How does chemistry inform what you do?
I really can't know enough chemistry as it pervades everything I do at work. The deeper my knowledge, the better I'll be at my current job, and the greater the chance I'll have of getting another.
Pros and Cons?
It seems that this job combines most of the good bits of being an academic and a PhD student; on the one hand I get almost total freedom to do what I like, I still spend most of my time in the lab, I get to teach and I get to be familiar with all the stuff that other people in the group work on but I don't have to write grant proposals or a thesis, take exams, or attend many meetings. It's pretty much how I think being a chemist should be. The main problems with the job are that it doesn't pay that well; although money is rarely a problem for me, I couldn't start a family or buy a house; the hours are pretty long, and are only going to get worse when I cross the Atlantic; and it isn't a long term career, as doing more than a couple of one or two year postdocs is widely considered a bad idea. It can also be stressful and frustrating.
A funny story?
Reading through what I've just written I guess I come across as pretty keen on chemistry, but it hasn't been a lifelong interest of mine. I wanted to study physics at university but sucked at math so I ended up studying materials science. That turned out to be a little too last-but-one century for me; the amount of time we spent learning about steel and concrete really put me off. After a year I switched to chemistry, but was a mediocre undergrad as I spent most of my time running the university mountaineering club and planned to get a job in the outdoor industry when I graduated. It wasn't until my final year masters project that things changed for me. Although I usually did much better in inorganic chemistry, I chose to join an organic research group that looked interesting on paper, but to my surprise it turned out to consist only of one mostly retired emeritus professor and a young - but extremely talented - postdoc. To hear those two talk about chemistry was amazing; it was like listening to a conversation in another language, and as they swapped stories about this academic or that, discussed the latest Nicolaou paper or just stood around cracking jokes I realised that the world of organic chemistry was much more interesting than I'd ever realised. I loved the history, the in-jokes and the community. I wasn't a great masters student, but I doubt anyone else in my year learned as much as I did during their project. Four years later I'm still a chemist. And I'm not ready to stop learning yet.
** This is not true.
On Monday, See Arr Oh over at Just Like Cooking posted on this non-obvious Diels-Alder reaction recently published by the Vanderwal group, suggesting that it'd make good problem session fodder. And I agree:
Fortunately, this tied in perfectly with my plans to run our group problem session next week on a pericyclic theme and so it was duly incorporated. If you're interested in what else featured, I also included a question on the origin of the metastability of Dewar Benzene (which I've blogged about before).
After a few easier questions I finished up by asking people to suggest a mechanism for this interesting sequence published a few years back.
Have you ever tried to look up famous chemists on Wikipedia only to end up misspelling their name or finding a more famous person who shares it? Although sometimes this can be frustrating, it can also be pretty funny. Here are a few amusing namesakes I discovered recently:
As well as being one of the leading figures in the organocatalytic revolution, according to wikipedia.org, "David McMillan is a British-Australian drug smuggler who is best known for being the only Westerner on record as having successfully escaped Bangkok's Klong Prem prison". A man of many talents. Apparently, Dave avoided recapture by his immediate acquisition of an umbrella once outside the prison walls... because escaped prisoners never carry umbrellas. Clearly a clever man.
2. Phil Baron
The real Phil Baran. Credit: Sexy Science
Although he tends to make the rest of us look bad and just won't stop writing review after review after review, I still get excited whenever he publishes something. Apart from all that chemistry and reviewing, I have just learned from the Phil Baron wikipedia page that he's also a "voice actor, puppeteer and songwriter who voiced Piglet in the Disney Channel live-action/puppet television series Welcome to Pooh Corner". Where does he find the time?