B.R.S.M. Yield isn't everything


And Another Thing…

While the recently misassigned structure of a certain binaphthyl compound has raised eyebrows here, and over at In The Pipeline, eliciting an entirely appropriate response from Chemjobber, I was reminded of an even sillier case of mistaken identity that was highlighted last year, but seems to have escaped comment on the blogosphere. The problem started back in 2007 when a paper was published in the Journal of Natural Products, where the authors claimed to have isolated a most improbable natural product from a fungus:

From J. Nat. Prod., 2007, 70, 989

Amazingly, nobody called bullshit on this until April 2011 despite the fact the paper was cited 32 times during that period. I mean, I still remember seeing the paper that blew away this structure, entitled "Is 2,3,4,5-Tetramethoxybenzoyl Chloride a Natural Product?", and just staring in wonder that such a question could be seriously posed in an ACS journal. Surely no one ever believed that is was?

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Four Days To Go!

From Chem. Soc. Rev., 2012, DOI: 10.1039/C2CS35116A

Just a quick post to remind you that I need your Colouring Competition entries by the end of Tuesday so I can write some kind of round up post in time for Nicolaou's birthday on Thursday. This weekend would be a good time to spend just 10 or 15 minutes messing around in Photoshop, the GIMP, or at a push, MSPaint. Heck, you can even print them out, colour them in and scan them if you don't have mad image editing skills. Not that it matters; I certainly don't. Give them to your children! If you're short of inspiration you can check out the entries from See Arr Oh and DrFreddy, or look at the latest Nicolaou review above.

Filed under: ANFSCD, Ask the audience | 8,748 views | no comments No Comments

(+/-)-Echinopine B

Vanderwal (ˈvændəˌrwɑːl)

v. Vanderwalled, Vanderwalling, Vanderwals

v. tr. To complete an impossibly short, but racemic, synthesis of a popular target e.g.


A Synthesis of Echinopine B

Vanderwal et al., Angew. Chemie. Int. Ed., Early View [GROUP] [PDF] [SI]

DOI: 10.1002/anie.201203147

Since their isolation in 2008 the echinopine sesquiterpenes have proved quite popular targets for total synthesis, probably thanks to their unusual and compact molecular architectures. Johann Mulzer, one of my favourite living synthetic chemists, succeeded in a beautiful first total synthesis just a year after their isolation, asymmetrically synthesising both natural products (starting from cyclooctadiene!) and assigning their absolute configurations in an excellent paper that somehow ended up in Organic Letters. The year 2010 saw rather a lengthy synthesis by Nicolaou as well as a paper  by Chen outlining studies that developed into a total synthesis last year, which I commented on at the time.[1] Until a couple of weeks ago, Mulzer led the pack needing a mere 20 steps from commercial materials, with Chen a close second at 24, and KCN's ponderous 39 step route languishing at the back. At the time it came out, I didn’t think Mulzer was doing too badly, given the dearth of oxygen in the target and the lack of obvious disconnections. However, the synthetic bar has just been raised by Vanderwal and co-workers, who recently reported a nifty 12 step, albeit racemic, total synthesis that I think should stay at the top for a little while.

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Where Did It All Go Wrong?

I’m sure life as an isolation chemist is hard. First of all, you have to actually find a source of interesting molecules, and while this sometimes involves diving in spectacular locations, or trekking through unspoiled rainforest to pick rare fruit, I’m sure it more often involves literally HPLCing shit or eviscerating four tons of eels. Furthermore, when you’ve actually got the compound, that’s only half the battle, as Nature is unbelievably creative at devising unique and surprising architectures to baffle the unwary. Synthetic chemists spend large amounts of time bewildered by NMR, and we get some pretty big clues from what we actually put in the flask to start with. Starting from scratch is even harder, even with the modern array of analytical equipment. Even the gold standard technique of X-ray crystallography isn’t perfect, and there have been some very famous natural products misassigned even with the aid of this breathtakingly powerful tool, including competition molecule diazonamide A, and kinamycin C.[1] Having said all that, looking at this recent example of a proposed natural product structure that was revised by synthesis, I have to say that I think I could have done a better job myself. Drunk.

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A Birthday Surprise for K. C. Nicolaou

Update 1930, 20-06-12: Just noticed a mistake in my haplophytine structure (cdx, png and jpg) - a mesyl group where there should be an OH. If you've already downloaded/printed this please get the new, corrected version before continuing. Sorry!

Also, check out the first entry, from DrFreddy over at Synthetic Remarks!

Before you hurry to  check JACS, I made this myself. The image, that is.

The ongoing trend towards more colourful graphical abstracts is a perennial topic for discussion around the blogosphere.[1] Rather than draw attention to recent crimes against chemical decency, many of which can be found at TOCROFL, I am today proposing something new.[2] As many will know, the current spate of increasingly lurid abstracts can be traced to one man, American Cypriot and legendary synthetic chemist K. C. Nicolaou. But when did it all start? The cover of Classics in Total Synthesis I, published in 1996, appears to be free of such visual pollution, but it seems that by 2003 when Classics II and his autobiographical Tetrahedron prize essay were published that the inveterate colouring in had begun, and his papers are now rarely seen without it. However, I'm not going to join the online castigation of this questionable new form of art. Far from it. In fact, as it's KCN's birthday in a little over two weeks from today, I propose the WORLD'S FIRST CHEMICAL ABSTRACT COLOURING COMPETITION!

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Happy Birthday… To Me!

This is an actual cake that my girlfriend made me. I'd share it with you if I could!

Well, I didn't think that this day would come, but I have now been blogging for exactly one year! One rainy weekend last June, I sat down and wrote my first three posts, all on recent total syntheses. At the time, Totally Synthetic had been dormant for several months, and I planned to fill the void left by its absence. I only had about ten months funding left for my PhD, and I didn't know if I'd stay in chemistry after I finished, so I was entirely uncertain about where this site was going. In retrospect, it was probably a pretty stupid thing to start when I was supposed to be working my hardest in the lab to finish up.

Although I was pretty nervous at first, it turned out that very few people actually read my early posts, and I discovered that it's really hard to promote your own blog if you wish to remain anonymous. However, thanks to some advice offered in a comment by Freda I created a Twitter account, and after a few links and retweets by Nature Chemistry and New Reactions, I finally got some readers! Fast forward to the present and, as of this morning, this site has got been viewed almost 104000 times, which is a response I could never have imagined when I started. In my third post, See Arr Oh (in his homeless, pre-Just Like Cooking days) left me some very encouraging advice in a comment:

People are always looking (although they may not seem like it) for erudite but approachable discussions of the literature. Many just don’t have the time or access to look themselves, so they’re happy to have you guide them through it.

The niche takes a while (says the guy who doesn’t manage his own blog!). Just keep writing about good, current stuff, and people will find you.

How right he was! As I started to experiment with different types of posts, I was surprised to see that many people were more interested in shorter, more varied posts than the long, detailed total synthesis-based posts I'd planned to write. In fact, I'm not even sure how to describe this site to people any more - with posts from explosives to etymology, from chemical history and biographies through to the latest stuff you'll never try from slightly disreputable journals, I think I've shed my label of a poor man's Tot. Syn.!

Right, I'm not got to ramble on any longer, as people come here to read chemistry and I try to keep the personal stuff to a minimum. Many thanks to you all for reading, commenting and getting the word out! A special thank you to Dr Freddy from Synthetic Remarks, who offered me space on his webserver after my hosting became too unreliable, set me up with my own domain, and continues to host this site. I don't know what I'm doing next, but hopefully I'll be writing another post like this one next June!




P.s. More science soon! If anyone has any good tips for things worth writing about, or is interested in guest blogging here, please get in touch or leave a comment!

P.p.s. Should you wish to celebrate this auspicious day, but find yourself sadly incapable of making a cake, then here's the recipe that was used for the one above. It's just a regular Madeira cake that's been dressed up a bit, but was quite tasty. Although I love to cook, I don't make many cakes, so this recipe is courtesy of my better half. Enjoy!

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Chemical Etymology 1: Introduction

Credit: xkcd (http://xkcd.com/1012/)


I still find myself encountering unfamiliar terms in the literature all the time. Sometimes in my favourite organic chemistry journals, but especially when I stray further away from ‘pure organic’ into biochemistry, pharmacology, physical organic chemistry and other areas I know much less about. Before (or after) resorting to looking up new words, I really enjoy taking a guess at what they mean based on the smattering of Latin and Ancient Greek I learned at school and picked up over the last few years as a scientist. Strangely, I also find that knowing where words come from really helps me remember them, and I’m much more likely to know what they mean when I see them again. I’m not a linguist, but it seems to me that actually just a few root words seem to crop up rather a lot, and I’ve found that being familiar with a handful can be pretty useful. The aim of this post, and probably a couple more over the next month is to try and teach people who have never considered the origins of chemical terms something new.

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A Funny Thing Happened On The Way To Hirsutene

Or: Why My Group Hate Me #13572

Apologies for the recent silence - I have just started a new (temporary) postdoc, and I have been busy with the reading for that. I am now an alkaloid chemist! The next few updates will be brief while I settle in.

Many research groups seem to have a weekly problem session, or something similar. In my experience, this usually means a rota (or something less formal) where people take it in turns to set a few chemical problems for everyone to have a go at. Often a sheet is produced, and handed out a few days before so people can have a chance to think/put the structures into Scifinder.

The problems themselves can vary a great deal, and are nowhere near as predictable as, say, undergraduate exams. A common layout is the 'synthesis blankout', where a synthesis from the literature is redrawn but some key reagents and intermediates are missing, to be filled in by the attendees. Alternatively, sometimes a bunch of short reaction sequences are taken from several papers, because they're interesting, or illustrate a particular theme. I've also seen a few more original approaches, such as this one, which I think I downloaded from the Ley group website a few years ago:

In the group where I did my PhD, the sessions were always run by students and postdocs, attendance was optional and the boss never came. Although you might expect that without a scary professor most of the group would go, as we all have to viva at some point, this turned out not to be case, and there was probably never more than a third of us present at any one time. I was a regular, and used to enjoy problem sessions - much like I enjoy crosswords, pub quizzes and, well, being an organic chemist - for the challenge. They're also a great chance to focus on chemistry outside of what your own group does. My PhD was on the synthesis of largely flat - and if not, racemic - heterocyclic natural products, so I tended to set questions about selective transformations in large, stereochemically dense molecules, in order to vicariously experience the thrills and tribulations of modern organic chemistry. Unusual or baffling transformations on seemingly simple systems were another favourite of mine, and I really enjoyed these recent offerings from DrFreddy over at Synthetic Remarks. In that vein, I offer you this question, which I recently set for my group:

Answers in the comments, or via Twitter!

Filed under: Ask the audience | 11,170 views | 9 comments 9 Comments