Total Synthsis?

We had our weekly journal club this morning. Interesting paper from a Korean group but maybe the ACS editorial office should wake up. D!

Curly Arrow - Established 18th October 2006

Merry Christmas and Happy New Year! I Hope that everyone is getting some well-deserved time off. I used to do a yearly post on visitor stats around the blogs birthday but forgot this year!. Since it was the 5th birthday on 18th October 2011 I have decided to have a look back at how things developed in the past year.
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From 18th October 2010 to 18th October 2011:
Absolute unique visitors: 34,488
Total visits: 61,799 (169 Visits/Day)
Average time on site: 1:25 minute
The 10 most frequent visitors identifiable:
(1) ETH Zürich
(2) University of Hull
(3) Queens University Belfast
(4) Universite de Liege
(5) Princeton University
(6) The Scripps Research Institute
(7) Oxford University
(8) University of Ghent
(9) The University of Nottingham
(10) Johann Wolfgang Goethe Universitaet Frankfurt 
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Top 10 countries that visit the blog:
(1) United States (18,348 visits)
(2) United Kingdom (8,642 visits)
(3) Germany (3,707 visits)
(4) India (3,016 visits)
(5) Australia (2,549 visits)
(6) Canada (2,490 visits)
(7) Switzerland (1,895 visits)
(8) Denmark (1,603 visits)
(9) Japan (1,497 visits)
(10) Belgium (1,366 visits)
D!

Let's Talk About TLCs Part 5 - Iodine Stain

The iodine stain is by far the easiest stain to prepare and use. The classic way is to simply have a chamber with some iodine crystals that you put your TLC plate into. The iodine vapours will react with many functional groups but is particularly good with unsaturated compounds (e.g. alkenes and alkynes) to give reddish brown spots (see TLC plate below). Another way to prepare the iodine stain is to mix silica gel with iodine crystals (see pic to the right). Stick the TLC plate into the red silica and wait a few minutes to develop your plate. This approach is a bit gentler and in my experience gives a better result. If you want to keep your TLC result for later remember to take a picture of your plate or circle the spots as they fade relatively fast. D!

Reverse Phase Silica - Sort of!

I'm sure that all the synthetic organic chemists will agree that column chromatography is something we simply couldn't live without. At our Department we use it in all its forms: Automated flash chromatography, Chromatotron, Prep. HPLC (Chiral and RP), Prep. TLC, old skool manual flash and DCVC columns etc. However, in spite of all this we all too frequently end up with stuff that is a major pain to separate. Just last week a colleague of mine, lets call him Bernard, told me he had used deactivated silica for purifying his compound - the only thing that had worked for him! So now you are probably thinking deactivated silica??? Normal lab terminology translates this to treating your silica with some amine base prior to use but this is not what Bernard was talking about. He found this paper (Procedure in the Supp. Info.) where they derivatise silica gel with ethyltrichlorosilane. Cheap reagents and a simple method. I guess the "deactivated" silica ends up being something between regular and reverse phase silica. Bernard simply packed a column with this stuff and put on our automated columning system to get a great result eluting with normal phase solvent mixtures. Excellent news for me and my people. We often end up with very polar compounds that will not come off a regular column or elute in fractions 1-5 on a reverse phase column.

Does anyone have any experience with this type of silica or something similar? Please let us all know by posting a comment. D!

Triazoles in Peptidomimetic Chemistry

Self Promotion time! Our review on 1,2,3-Triazoles in Peptidomimetic Chemistry was just published in EuroJOC.

Useful stuff if you are working in the peptidomimetic area. You can get it here or by emailing curlyarrow@gmail.com. D!

The Sand Bath - An Alternative to the Oil Bath

Yes, I am still alive! I have been out of the lab for a loooong time so the inspiration hasn't been there. However, I am now finding myself in the lab again and it appears that I will get to stay there for a while. And today inspiration struck.

Let's talk about oil baths. Good way to heat stuff up in a controlled way, BUT, what a bloody mess they are. The oil becomes disgusting after a while, the glassware gets nasty, ocassionally oil baths break and make the mess from hell....
So whenever possible I use an aluminium heating block. However, we have a limited number of these in a limited number of shapes and sizes. When a heating block isn't available my next choice is a sand bath. These are traditionally used when you have to heat something to a ridiculous temperature that oil can't handle. However, I use them for any reflux (see picture). The problem with these things is that heat transfer isn't particularly effective so it's only really good for reflux and not for heating something at a well defined temperature below the boiling point. Also it can be quite tricky for the sand bath to heat up in a well ventilated fume hood so it is generally a good idea to wrap a bit of aluminium foil around the bath to get the heating going. D!

Is there a Future for Organic Chemists in the Pharmaceutical Industry outside China and India?

I have copy/pasted the headline for this post from the editorial in the most recent issue of Organic Process Research and Development. It's a good question that is being asked and I believe that the answer is YES. However, we really need to come up with something new to justify our existence. The Chinese and others are just as good as us at doing Med Chem SAR working their way through methyl, ethyl, propyl, futile...but they can do the work at a much lower cost. The same thing that happened to the textile industry sometime last century is happening to the pharmaceutical industry. The design is made in the western world but the actual product is manufactured at some cheap site in Asia. The way forward is to invent new ingenious stuff. Start biotech companies with crazy, innovative new technologies, start working at the biology/chemistry interface modifying proteins; oligonucleosides etc. in predictable ways for use a medicinal agents and so on. Ultimately this development is a good thing. It is forcing us to think and evolve. In the end humanity will benefit from some great new discoveries and technologies that will spring from the effort we put into this. So get up and go invent something brilliant that will make the world a better place. D!

If it works don't mess with it!

I'm currently in Brussels vistiting a collaborator. The research groups lab is absolutely fascinating and contains several old school mechanical contraptions that do a great job.
For your glassware drying pleasures:
For melting point determination (not sure how useful this device is but its looks cool):
It's not always necessary to upgrade to an expensive model with digitals controls to achieve the goal. Check out this solid phase synthesis shaker and the fantastic sound it makes - music to my ears. D!

NMR Impurities Tabulated

If you didn't already spot this useful paper on NMR impurities you should go get it now. An excellent addition to the classic paper by Gottlieb et al. that you can access here. D!

PhD in Medicinal Chemistry

Design and synthesis of the first selective ligands for the GPRC6A receptor – a novel human G-protein coupled receptor with unknown physiological function

More info at this web site.

DO NOT email us but please follow the application procedure at the bottom of this web page.

There are links to all necessary information on the same web page.

D!