Anti-GMO activist sees the light!

I picked this up at one of my favourite blogs (in the pipeline) and simply have to share it. A former fanatical anti-GMO campaigner read some scientific papers and realised his wrong doings. What a fantastic start to the New Year. It makes me think that there still may be hope for humanity when someone like Mark Lynas can come around and realise his mistakes and openly admit it. As a minimum you should watch the first 6 minutes of his presentation at the Oxford Farming Conference. D!

Guidelines for giving a truly terrible talk

I'm giving a presentation in a month's time which reminded me of the stuff below. Unfortunately, I can't remember what web site I got this stuff from but apparentely it's from "35-mm Slides: A Manual for Technical Presentations", by Dan Pratt og Lev Ropes. Surprisingly many scientists seem to use these guidelines. Here we go:

"Strict adherence to the following time-tested guidelines will ensure that both you and your work remain obscure and will guarantee an audience of minimum size at your next talk. Continuity of effort may result in being awarded the coveted 5:00 P.M. Friday speaking time at the next national meeting." Slides:
(1) Use lots of slides. A rule of thumb is one slide for each 10 seconds of time allotted for your talk. If you don’t have enough, borrow the rest from the previous speaker, or cycle back and forth between slides.
(2) Put as much information on each slide as possible. Graphs with a dozen or so crossing lines, tables with at least 100 entries, and maps with 20 or 30 units are especially effective; but equations, particularly if they contain at least 15 terms and 20 variables, are almost as good. A high density of detailed and marginally relevant data usually prevents penetrating questions from the audience.
(3) Use small print. Anyone who has not had the foresight to either sit in the front row or bring a set of binoculars is probably not smart enough to understand your talk anyway.
(4) Use figures and tables directly from publications. They will help you accomplish goals 2 and 3 above and minimize the amount of preparation for the talk. If you haven’t published the work, use illustrations from an old publication. Only a few people in the audience will notice anyway.
Presentation:
(1) Don’t organize your talk in advance. It is usually best not to even think about it until your name has been announced by the session chair. Above all, don’t write the talk out, it may fall into enemy hands.
(2) Never, ever, rehearse, even briefly. Talks are best when they arise spontaneously and in random order. Leave it as an exercise for the listener to assemble your thoughts properly and make some sense out of what you say.
(3) Discuss each slide in complete detail, especially those parts irrelevant to the main points of our talk. If you suspect that there is anyone in the audience who is not asleep, return to a previous slide and discuss it again.
(4) Face the projection screen, mumble, and talk as fast as possible, especially while making important points. An alternative strategy is to speak very slowly, leave every other sentence uncompleted, and punctuate each thought with "ahhh", "unhh", or something equally informative.
(5) Wave the lights pointer around the room, or at least move the beam rapidly about the slide image in small circles. If this is done properly, it will make 50 % of the people in the front three rows (and those with binoculars) sick.
(6) Use up all of your allotted time and at least half, if not all, of the next speaker’s. This avoids foolish and annoying questions and forces the chairman to ride herd on the following speakers. Remember, the rest of the speakers don’t have anything important to say anyway. If they had, they would have been assigned times earlier than yours. D!

Off to Chicago

RACIOC 22 Highlights Part III

Okay one final post on the conference before I move on to other stuff. Chris Braddock from Imperial College, UK gave an interesting talk entitled: "Towards a Biosynthetically-Inspired Chemical Synthesis of the Obtusallenes". Obtusallenes are halogenated marine natural products and there's at least ten structurally similar compounds within this family (two example are shown to the left). It was nice to see how much thinking had gone into Chris' research. A lot of speculation on a possible biosynthetic pathway and even a publication in Organic Letters on these reflections (DOI: 10.1021/ol062520q) which you don't see that often. I wasn't familiar with the NMR method for determining the location of bromine- and chlorine-substituents that he employed. It looked very useful so if you can't get those crystals for your X-ray you may consider giving that a go (Raynes et al., Mag.Res.Chem., 1997, 35(2), pp. 141-143).
I have spent a significant part of my life attempting to make cyclopropanes and fancy myself rather knowledgeable in this particular area so you can imagine my surprise when Professor Andy Phillips from University of Colorado mentioned the Kulinkovich cyclopropanation out of the blue (talk entitled: "New Reactions and Strategies for the Synthesis of Complex Natural Products"). I have to admit that I was a full-on Kulinkovich virgin. It's a pretty funky reaction producing 1,1,2-trisubstituted hydroxy-cyclopropanes. These are generally not easy to make so I'm surprised I hadn't seen this stuff before. I'm not sure if anyone has attempted to make an asymmetric version of the reaction but in any event using optically active starting materials Professor Phillips Group managed to make optically active stuff (see below).

I didn't get the yield or dr and I don't know if the stuff has been published yet. However, there's a nice entry in Organic Syntheses (OS) on the Kulinkovich cyclopropanation giving two examples (71 and 80% yield to give one diastereoisomer) as well as some background and the mechanism (see mechanistic explanation from OS below).

Anyway, a very good talk by Andy Phillips (and many others that I haven't mentioned). I think I've been beating this conference to death by now so let me finish off with three quotes from oral presentations that made me laugh: (1) ...thio-ether mutant..., (2) ...encourage to die..., (3) ...good quality frog... D!

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!

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 Zürich 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!

RACIOC 22

In about two hours time I'll be busy socialising at The 22nd Royal Australian Chemical Institute Organic Conference (RACIOC 22) here in Adelaide, South Australia. I'm giving an oral presentation on Wednesday at 11 am on the synthesis of cyclopropane amino acids. So if you are attending the conference come and check it out. Hopefully, I'll have loads of stuff to post from the conference to get the blog going at full steam again. Anyway, gotta go. Still haven't finished my slides and I've got one last NMR to run. D!

Adelaide Synthetic Symposium 2006 Part II

As I mentioned previously Professor Mukund Sibi also presented at the symposium. His talk was entitled: "A New Dimension to Enantioselective Catalysis - Templates Come to the Rescue". Sibi is all about developing new methodologies for asymmetric synthesis. However, the approach is different from what other people in the area are doing. Basically, his concept is to attach a template to the molecule you would like to perform your asymmetric chemistry on. To achive asymmetric induction he now chucks some chiral Lewis acid into his flask followed by the reagent that is going to react with his substrate. The result is high yields and excellent ee's. Okay I think it's time for some structures to clarify matters. Sibi has done a whole bunch of asymmetric radical additions that goes along these lines:A very important detail is that the template is a simple, achiral unit. The sole purpose of the template is to coordinate the Lewis acid well, exert rotamer control and as a consequence give good facial selective for the incoming nucleophile. Now as I mentioned before this principal works very well for many reactions. The Lewis acid is used in sub-stoichiometric quantities (generally 10-20 mol%). The radical stuff that I outlined above is okay cool but I personally like his stuff on pericyclic reactions better. Back in 2001 he published a very interesting paper in JACS (DOI: 10.1021/ja016396b) on Diels-Alder reactions:

So this is taking things one step further by using a pyrazolidinone template with a substituted nitrogen. What they are achieving here is what can be described as relay induced enantioselectivity by nitrogen inversion. In other words, you use a achiral pyrazolidinone template and throw your chiral Lewis acid in that upon coordination will favour one asymmetric conformation of the template. Pretty funky stuff. You really need to check this paper out to get all the details. Anyway, it works very well. Here's some numbers:

Notice that template 11 with no relay unit is poor proving their point.

More recently Sibi has done some work on enantioselective [3+2] cycloaddition of nitrile imines (DOI: 10.1021/ja051650b). This time using their basic system with no relay. This stuff also works exceptionally well giving some heterocyclic compounds that might be appealing to people doing a bit of medicinal chemistry:

This time there's also regioselectivity issues. However, they solve this and all other associated problems elegantly producing the desired dihydropyrazoles in excellent yields and ee's.

I recommend reading these two JACS communications. Good thorough science and very well written papers. D!

Adelaide Synthetic Symposium 2006 Part I

They let me out of the lab today. It was time for the annual Synthetic Symposium that was held at Flinders University this year. As usual they fly two big wigs in to present stuff. The remaining talks (6 this time) is given by PhD students. This year the big wigs were Professor Martin Banwell from the Australian National University and Professor Mukund Sibi from North Dakota State University. Both of them gave very interesting talks indeed. Apparently what these guys do is old news. Well It was news to me so here's a brief crackdown on what Banwell had to say. Banwell is a total synthesis man and today he was talking about the synthesis of compounds such as Brunsvigine, Complicatic Acid, 11-O-Debenzoyltashironine etc. The talk was entitled "Chemoenzymatic Methods in Synthesis" and it was the whole chemoenzymatic bit that caught my attention. Basically they are taking simple substituted benzenes and dihydroxylating them. Truly amazing stuff:As Banwell pointed out the example with styrene is unbelievable and the ee's are through the roof! Moreover, the concept isn't limited to monosubstituted systems and more than 250 metabolites of this kind are known by now. So a couple of things immediately spring to mind. What scale can you do this sort of thing on and how do you get the other enantiomer of your product if that is what you are after. Well Banwell was on top of things and addressed these matters during his talk. Firstly, this stuff can be done on big scale. In the case of bromo- and chlorobenzene they obtain 35 grams of stuff per litre of fermentation broth which is pretty damn impressive. If you want the other enantiomer things are a bit trickier. However, Allen et al. have developed a method where the enantioselectivity is switched by introducing an iodine substituent that can be removed after the dihydroxylation:A nice and simple solution to a complex problem that was published in Chemical Communications in 1995 (DOI: 10.1039/C39950000117). Anyway, this was just Banwell's introduction. He went on to talk about the total synthesis of a whole range of natural products starting from these metabolites. Most of it was unpublished stuff so I'll be a good boy and not post it all here just yet. Enough for now. I'll post what Professor Sibi had to say some other day. D!