While sorting through the photos from last fortnight's conference/holiday I found this beautiful shot of the lecture theatre complex in which I gave my talk. It's not quite finished... but where is it? Answers on a postcard!
P.s. This is not a joke. I seriously attended a 4 day conference here. I like the yellow curtains on the right, leading up to the entrance. The phrase 'lipstick on a pig' springs to mind.
Okay, so it's not Wednesday, but I've just finished this and I'm not going to sit on it for another 4 days. Merry Christmas!
The Total Synthesis of Chlorophyll a
Full Paper: R. B. Woodward et al., Tetrahedron, 1990, 46, 7599-7659 [PDF]
Communication: R. B. Woodward et al., J. Am. Chem. Soc., 1960, 82, 3800 [PDF]
Lecture: R. B. Woodward, Pure Appl. Chem., 1961, 2, 383 [PDF] FREE!
One thing I enjoy most about reading Woodward’s work is the variety of targets and natural product classes he worked on. He conquered steroids, alkaloids, polyketides and amino acid derivatives with equal aplomb, pushing the limits of complexity in each field, and always looking for the highest peak to climb. Woodward’s synthesis of chlorophyll a has been somewhat overshadowed by his truly epic collaborative synthesis of vitamin B-12 (some years later), but for its time was an outstanding accomplishment, unmatched in the field of porphyrin chemistry. Unfortunately, most books on classic or collected total syntheses only cover B-12, but plenty of interesting chemistry (as well as breathtaking experimental skill) was brought to bear in this earlier, simpler campaign. I’m not going to write anything here about the importance of chlorophyll as it's a bit obvious, so on to the chemistry.
I was just going to let you all wonder (or not) where I've been for a couple of weeks more, but it turns out that having readers makes me feel really guilt for just disappearing. So, for the last two years, among other things, I've been working on a total synthesis project. After more than a few false starts, dead ends and detours, things picked up and progress has been good for the last couple of months, with the end finally in sight. To make things more interesting, I desperately wanted to finish the darn thing for a conference abroad at which I'm speaking next week. This effort has left me with little free time for things I enjoy, blogging being an early casualty. Fortunately, I completed my synthesis on Tuesday (with 4 days to spare!), the data match and I'm leaving triumphantly this Sunday to go and brag about my work. I'm out of the country until 21st December, after which I look forward to having a lot more time for writing again, and I'll get some posts up as soon as I can. Until then there's not much point checking this blog. I have about half a WW post on Woodward's epic synthesis of chlorophyll A, which I hope to finish while I'm away, and that'll probably be the first thing up when I get back.
Thanks for your patience!
P.s. An actual quote from my supervisor on Tuesday: "do you think you can get the paper written before you leave?". Don't count on it...
Update 20-11-2011: Reference added and a couple of mistakes removed. Why can I never see those the first time?
Scalable Enantioselective Total Synthesis of Taxanes
The taxanes are a large family of 350 or so natural products, of which the best known is taxol itself, a multibillion dollar anticancer drug with a rich and storied history, whose name and distinctive tetracyclic system are instantly recognisable to most organic chemists. Taxol itself has already been the subject of 7 epic total syntheses (see BRSM Reviews: Taxol In 10 Minutes if you need a quick reminder), all using conventional functional group lead approaches to bond formation. Nature's (and Phil's) approach is a bit different, though, as we'll see.
If you're reading this then I reckon you've probably heard of taxol, as it's one of the most talked about synthetic targets of all time. It's a molecule with a fascinating history, from its isolation and structural assignment in 1971, to discovery of its potent activity and interesting mode of action, and the ensuing scrabble to solve the supply problems plaguing its development as a drug. Its rise to success as a billion dollar pharmaceutical was stellar, and is one of my favourite examples of how useful and important synthetic organic chemistry is. Although it's been 5 years since the most recently reported synthesis of taxol, last week's Baran synthesis of taxadiene (following his cyclase-oxidase mimic plan for elaboration of this hydrocarbon into taxol) seems to have again gotten chemists talking excitedly about this target. After overhearing things like 'didn't Nicolaou make it first?', 'there've only been x syntheses so far' (where x is 0-6) and other such misinformation in our office I've decided to take action. Yes, there are already numerous reviews, book chapters and even entire books on this subject, but it seems that a lot of people don't have the time or inclination to read them. So, here's a brief summary of the 7 syntheses published so far, in the order they were completed. Hopefully this'll help put recent developments in perspective.
Enantioselective Total Synthesis of (-)-Acetylaranotin, a Dihydrooxepine Epidithiodiketopiperazine
This week saw another brilliant synthesis from the still fairly new Reisman group over at Caltech, this time an epidithiodiketopiperazine (ETP), the group's first. These interesting secondary metabolites have so far only been isolated from fungi, and owe their toxicity to their disulfide bridges that generate reactive oxygen species by redox cycling. Although ETPs have been popular targets for the last 40 years, and the field has seen some impressive chemistry from Kishi in the 70s to more recent efforts by Movassaghi, Overman and Nicolaou. More challenging still are the dihydrooxepine containing ETPs such as acetylaranotin, which has stood unconquered since its isolation 1968, and in fact no synthesis of such a compound has been reported, until now.
Hi all! Although this news is actually over a week old (and things are still in progress), I have an announcement to make. As many of you may have noticed, my old webhosting sucked - my domain was unmemorable, and when you did find the site it was often down for some reason. Well, thanks to a generous gift from DrFreddy over at Synthetic Remarks I now have a new domain name, and some decent hosting to back it up! So, the reason for this post is twofold: firstly, to tell you all to update your bookmarks for I can now be found at brsmblog.com and secondly, to again thank DrFreddy for helping out a poor student - this is easily the nicest thing anyone's done for me all year!
By way of warning I should say that the database which powers the blog is still over at eristocracy.co.uk, which is slowing things down at the moment but it will hopefully be migrated soon, as are the schemes of posts written before last week because I can't seem to get the links to change to the new server. When these issues are resolved then everything should be much better. In the meantime, please be patient and expect things to be a little shakey for the next week or so while I work things out!
Note: In my opinion, it would be fairly ill advised to attempt any of these.
So, wax. According to wikipedia, a wax is just a plastic/malleable compound that melts slightly above room temperature to give a non viscous liquid. As this definition doesn't stipulate any chemical properties, there's a pretty large number of compounds which fall into this bracket, and so waxes from different sources can have very different chemical compositions. Wax from natural sources such as insects and animals tends to be composed of the esters of various fatty acids with long chain alcohols, whereas synthetic waxes tend to be simple mixtures of various long chain hydrocarbons. Earwax is different again. Regardless of its provenance, wax can be a pretty useful substance, with myriad uses around the lab. Here are the first five I can think of; no doubt there are others!
Update 26/11/11: Link to newly available SI now added!
Update 30/10/11: Also, Tot. Syn. now has a post on this.
Update 29/10/11: Covered in more colours over at synthetic nature. Check it out!
Carreira et al., Angew. Chem., 2011, Early View
Here's an interesting synthesis from a couple of weeks ago out of the Carreira lab - the first synthesis not only of daphmanidin E itself, but of any alkaloid of its family and skeleton. The daphmanidins constitute a recent addendum to the already fairly diverse class of alkaloids isolated from Daphniphyllaceae, with today's target only reported 5 years ago. Presumably, exciting features like "moderate vasorelaxant activity on rat aorta" and that well nested central bicyclo[2.2.2]octane ring make them tempting targets...