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!

5 comments:

Tom said...

Hey Dan, I think the ecstasy was alleviating the side effects of long term use of the drugs usually used to control Parkinson's. Definitely an excellent talk and a good demonstration of an exciting applied project.

Daniel Sejer said...

Yes that's right the side effects of L-DOPA long term use are suppressed by Ecstasy. Yeah I guess that isn't clear from the way I've written it. Thanks for that comment. D!

Nick said...

Hey Daniel, thanks for the shout-out. wow, I made it to the blogosphere - live the dream!

cheers.

Anonymous said...

interesting post on tenderbutton about L-Dopa (quite a similar structure to MDMA) and MPPP (street heroin, the reverse ester of demerol) and how a byproduct of the bathtub synthesis of MPPP can lead to a MPTP byproduct, which mimics the effects of parkinson's, and is now used in Parkinson's studies...look up MPTP on wikipedia for the story...

PMP said...

The Ando protocol works even better with o-substituted phenol esters. Also, excess sodium (NaH/NaI) helps.