Tuesday, February 20, 2007

RACIOC 22 Highlights Part II

It's actually great writing about this conference a couple of weeks later. It gives me another opportunity to think about stuff. Well I'm still not finished with the first day of the conference. I have to mention a talk given by PhD student Nicholas Aberle. Firstly, he's from an Australian Institution I never heard off: The Walther and Eliza Hall Institute of Medical Research in Melbourne. Judging by the stuff I saw at the conference this institution has a first-class Medicinal Chemistry Group. Nick works for Dr Jonathan Baell in the Structural Biology Division and gave an excellent talk entitled "The Trouble with Spiroleucettadine". The trouble here is the fact that the structure reported in the isolation paper (DOI: 10.1021/jo048789+) doesn't match what Nick and others in the area have synthesised. However, this time it's not merely a question of the wrong diastereoisomer being reported. It seems that the overall structure is significantly different from that reported. Nick did a whole bunch of NMR based modelling (Inspired by last years LaClair / Rychnovsky incident. DOI: 10.1021/ol0611346) and found a lowest error structure very different from the proposed structure. A very interesting talk indeed because Nick discussed the pros and cons of the modelling approach. Moving swiftly on, don't you just hate those talks were people are doing some random reaction because they can (usually producing some random heterocycle) that they don't have a clue what to do with and hence they proceed to do every common reaction in the world on their product(s). Spending a 20-30 minute presentation presenting Grignard on aldehyde followed by Wittig on aldehyde followed by reduction of aldehyde followed by oxidation of aldehyde...I hate that shit. It makes okay posters and shitty talks. There you have it. I've been holding it back for years. Speaking of posters and poster sessions, this is my favourite conference activity. The poster sessions were very well planned and executed (not enough free drinks and nibbles though) and there were some really good posters. I work a fair bit with dienes which occasionally can be a bit problematic. Professor Michael Sherburn's group works with polyenes so their posters were very interesting to me and I picked a couple of interesting things up. Alistair Longshaw's and Laurence Kwan's posters were particularly good. Firstly, how do you make a cis-alkene from an aldehyde? I thought that the Still-Gennari reaction was the way to go (see below).
However, this approach has certain drawbacks such as the cost of the reaction. Interestingly, in 2000 Ando et al. published a paper (DOI: 10.1021/jo000068x) using a much simpler alternative (Ando's reagent if you like, see example from the Sherburn Group below).

Also, I never realised that glassware goes acidic at high temperature and hence your polyene will polymerise as mad. The problem can conveniently be solved by adding some propylene oxide to the reaction mixture that will mop any acid up. Long term storage of polyenes is also a problem due to polymerisation. To get around this problem I normally dissolve my diene in hexane or dichloromethane and store it in the freezer. However, an even better way of preserving your compound is to dissolve it in benzene and freezing it in a solid benzene matrix. Finally, I have to mention Dr Matthew Piggot from University of Western Australia. Easily the best presentation that I attended at the conference. Matt gave a talk entitled: "Redesigning the Designer Drug Ecstasy" which was extremely interesting and very well presented. His work is based on the discovery by a young Englishman with Parkinson's disease who discovered that when he went out clubbing and took some Ecstasy virtually all his Parkinson's symptoms went away. He showed some videos of the English dude trying to drink a cuppa tea on placebo and then on ecstasy - the difference was unbelievable.

Now obviously you can't just administer Ecstasy to Parkinson's patients so Matt is trying to make Ecstasy analogues retaining the beneficial effects without the neurotoxic and psychoactive side-effects. The synthesis of the MDMA analogues isn't particularly interesting (see above). Short and simple giving him rapid access to a whole bunch of analogues. The best of luck to Matt on his Ecstasy project. To be continued....D!

Sunday, February 18, 2007

RACIOC 22 Highlights Part I

So I'm finally recovering from the conference followed by a pile of grant proposals and other stuff. Overall the conference was pretty good. The conference was a joint physical organic and organic conference and they attempted making sessions of general interest to everyone which is commendable but it didn't really work for me most of the time. Nevertheless, a lot of very good stuff was presented. One of the highlights was a talk given by Professor Michael Sherburn from the Australian National University (ANU) in Canberra entitled "Everything You Ever Wanted To Know About Synthesis". He's an amazing entertainer. I just wish he would start singing and dancing too. He really reminded me of Frank Sinatra and his chemistry is absolutely brilliant - Diels-Alders all the way. He showed some interesting work using dendralenes (e.g. DOI: 10.1021/ja053772+): Kerrie Austin working for Professor Banwell (also at ANU) gave a good presentation on her work with (-)-Complicatic Acid (see structure below) and (+)-Hirsutic Acid C. I've mentioned this work before and there wasn't much I hadn't seen before. However, I have to show my complete ignorance regarding Mander's reagent. It's quite a useful reagent for doing stuff like this (didn't spot the yield for this reaction though): The conference really turned out to be a useful reagents and techniques conference. Professor Erick Carreira from ETH in Z├╝rich gave an excellent presentation as always. He showed some really interesting work using sulfamic acid as an ammonia equivalent in allylic substitution reactions. He showed a whole bunch of reactions and it looked very convincing indeed. Here's an asymmetric example using one of Ben Feringa's ligands (unoptimised, unpublished etc.):With some development this stuff looks like it may be quite useful. To be continued....D!