Off to Chicago

Gone Fishing

Penfolds Koonunga Hill - 30th Anniversary

I was looking for a Penfolds Bin 51 Riesling in the local liquor store the other day but couldn't find it so I decided to ask the staff if they had any. The proprietor told me that he generally didn't stock Penfolds wines which struck me as odd since Penfolds is the most iconic Australian winery and located only a short drive from where we where. Anyway, a long discussion on the quality of Penfolds wines before and after the acquisition by Southcorp and more recently by Fosters ensued (as you would expect the quality hasn't exactly improved). Anyway, why am I writing all this here? Well as it turned out he did have some special release Penfolds Koonunga Hill to commemorate the 30th Anniversary of the first release. The bottles have had special sleeves designed for them making it virtually impossible to sell the stuff since they look ridiculous. However, the sleeve on the Chardonnay was so funny I ended up buying a bottle (Check out the photo). The bottle is "decorated" with the periodic table of the elements and the structure of what seems to be cyclopentyl-methyl-carbonate (or something?). What have the marketing guys at Penfolds been smoking recently? Unfortunately, the stuff tastes terrible so I wouldn't recommend buying it. D!

How (not) to get rid of old diethyl ether

These darn old containers of diethyl ether that you need to get rid of... have you ever considered opening them with an axe and then pour them down the sink?

"A University of Washington pharmacology professor pleaded guilty in federal court today to charges of illegally dumping a chemical down a laboratory sink.

Daniel Storm, 62, last June broke open five containers of ethyl ether with an ax and dumped the contents, according to a release by the U.S. Department of Justice. UW health and safety inspectors had surveyed Storm's lab and determined that five containers of ethyl ether, which is highly flammable, needed to be disposed, but Storm didn't want to pay $15,000 out of a lab operations account to get rid of the substance properly. Storm then concealed the dumping, according to the Justice Department.

Under the terms of the plea agreement, prosecutors have recommended Storm be given probation when he is sentenced June 18. He faces a maximum five years in prison and a $250,000 fine.

Storm continues to work at the UW, where he faces an internal disciplinary process."

Well, as this post in The Seattle Times illustrates, it is - quite surprisingly - not too good an idea!

C!

Gurrs Microscopical Stains and Reagents

Don't you just love the way they used to store chemicals back in the day when men where men and women were women? We use a fair bit of Rose Bengal as a triplet sensitiser for the photochemical synthesis of 1,2-dioxines from dienes and oxygen. At the moment we are using some top-quality Rose Bengal from the world renowned chemical supplier Gurr:

Chemicals just don't come in containers like this anymore. If Sherlock Holmes ever used Rose Bengal he would most certainly have been a Gurr-man. Unfortunately, I haven't been able to get a new catalogue from George T. Gurr. I did however find this add for his products in Journal of Physiology (March 1953, Vol. 119, No. 4):

I wonder what happened to goode olde George and his microscopical reagents. D!

Quinine

Flipping through C&EN brought my attention to a recent review published in Angewandte Chemie (DOI:10.1002/anie.200601551) about the history of quinine synthesis. If you like (somewhat lengthy) stories about the history of chemistry and natural product synthesis, you might want to print this one out for bedtime reading.

And don't forget to drink a gin and tonic now and then to keep the malaria away! C!

A Column Apart

It's quiz time. Check out the flash column below. I may look like any other flash column but it is a truly unusual little fella. This is the first chromatography column of this kind I have ever put eyes on. I admired it for quite a while together with the other guys in the lab. We were all there for the packing and loading. Amazing stuff...our presence really freaked the guy running the column out. I don't think he grasped the significance of what he was doing. Anyway, what do you think is so special about it? D!

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!