Monday, April 23, 2018

Industrial Postdoc in Chemical Development of Green Solid-Phase Peptide Synthesis

It's been awfully quiet here in recent years. However, you readers are still very active on the blog and it clearly continues to be a good resource for synthetic organic chemistry students, which is great. Last year I decided to say goodbye to my University career and move on to a position in the pharmaceutical industry. I've had a lot of questions regarding why I did so. It's a rather long story so I will reserve that for another time. Anyway, to get to the point the reason for posting is that I am looking for a Postdoc for our department. If you are an experienced peptide chemist interested in joining our team and can see yourself having a career at Novo Nordisk in Denmark in the long term you should have a look at our job ad hereD!

Friday, April 28, 2017

Catalytic Hydrogenation - A Farewell to Alcohol(s)

We have a project in my group on bitopic ligands targeting the adrenergic receptors. We recently published a perspective paper on the topic that you can check out here. Anyway, today we had a project meeting regarding the synthesis of bitopic salbutamol analogues.
To this end, one of the guys wanted to synthesise an epoxide as outlined above. However, to his (and everyone else surprise) even under mild conditions he managed to loose both of his benzylic alcohols in the process. The crude product is of excellent purity and he isolated the over-reduced phenol in >90% yield.

This is a common problem but it really is trial and error. I would say that the case above is the most extreme example I have seen considering that it was run at atmospheric pressure and room temperature. It brought memories back from when I was a PhD student. The very last reaction I did in the lab was an attempt to reduce an alkene, however, as you can probably guess what I got out as the major product was the deoxygentaed molecule. However, this reaction was somewhat more messy than that above and the desired molecule may have been hiding in the mixture as well. D!


Wednesday, March 01, 2017

Reproducibility!

I guess it is old news but it only caught my eye today at the BBC website. Apparently Nature did a survey last summer (2016) were scientist were asked if they had "failed to reproduce another scientist's experiments"? What really surprised me was that only 70% on average said yes to that question. Obviously, scientists from all disciplines participated in the survey and chemistry did better in reproducibility than biology and medicine (when judged by themselves) but it looks pretty bleak overall. In synthetic organic chemistry, I would estimate that >95% of chemists have been unable to reproduce a published synthesis (as in get any of the desired molecule and not necessarily just the same high yield). Personally, I have had methods across the impact factor landscape fail in my hands, from Synlett to Nature Methods. On more than one occasion everything has just decomposed and gone black. Unless it is published in Organic Syntheses it's a bit of a lottery. Anyway, both articles are quite interesting and worth reading (although they are somewhat depressing). D! 

Monday, February 20, 2017

Dry Column Vacuum Chromatography (DCVC) - The Movie!

I have on several occasions been asked to make a DCVC video tutorial and quite liked the idea of doing so. Thus, I have started my acting career as you can see in the video below. I think the video will be a useful guide for first time DCVCers. For more info you should consult this and this blog post on DCVC. Many thanks to the University of Copenhagen's Communication Department, in particular Jacob Lejbach Sørensen, for investing some time in making this possible. D!


Friday, September 05, 2014

Total Recall - Synthetic organic chemistry is kinda slow and complicated!

To everyone's surprise I spent a day in the lab the other day doing some actual real life research. I forgot how hard, slow and complicated that stuff is. It would probably not be a bad idea for supervisors to leave the office and spend a day doing some lab work occasionally. I certainly appreciate what the guys are doing more after that ordeal. During my brief lab exposure I was reminded of the common messy lab balance problem. It is almost more common to find the balance littered with chemicals, dirty spatulas etc. than in a clean and tidy state. Anyway, the guys in my lab have sorted this out. A panda seems to do the trick. D!

Friday, December 27, 2013

Curly Arrow - Established 18th October 2006

It really is becoming the rule rather than the exception that I forget Curly Arrow's birthday. Its been running for 7 years now and as always here are some stats on the year that has passed. As you can see the lack of new posts really isn't deterring people from using all the info posted here over the years (Although visitor numbers are in decline for the first time). Hopefully I can squeeze a few post out in between everything else in 2014. D! 

From 18th October 2012 to 18th October 2013:
Absolute unique visitors: 36,032
Total visits: 42,428 ( 116 visits/day)
Page views: 68,627
Average time on site: 2:24 min
Top 10 most frequent visitors identifiable:
(1) University of California San Diego
(2) Oxford University
(3) Universite de Liege
(4) Johannes Gutenberg-Iniversitaet Mainz
(5) The Scripps Research Institute
(6) University of Cambridge
(7) University of California Irvine
(8) Stanford University
(9) ETH Zürich
(10) Columbia University
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Top 10 countries that visit the blog:
(1) United States
(2) United Kingdom
(3) India
(4) Germany
(5) Canada
(6) Australia
(7) Japan
(8) Denmark
(9) France
(10) Netherlands
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D!

Monday, August 12, 2013

Free Ligands - The Calcilytic Agent NPS2143, a Calcium-Sensing Receptor Modulator

We recently synthesised a significant quantity of the calcilytic ligand NPS2143 for our research programme on G protein-coupled receptors. NPS2143 is a negative allosteric modulator of the human calcium-sensing receptor and as such an important pharmacological tool compound. Recently, we developed and published a synthesis of optically pure NPS2143 in Beilstein Journal of Organic Chemistry (Open access journal that you should check out).
Anyway, now we have come to realise that we have a lot of this compound on the shelf that we are highly unlikely to ever use. So the idea to simply give the compound away to anyone that needs some free high quality NPS2143 popped up. So here we go! If you would like 5 mg of optically pure NPS2143 and you can fulfil the requirements below we will ship it to you:
  • You are an employee at an academic institution (Associate or Full Professor)
  • You will only use the compound for non-profit academic research purposes. Please provide a brief description (will be treated confidentially)
  • You can pay the shipment costs by courier (alternatively we will ship it by regular mail)
  • You will be kind enough to cite our paper "Synthesis of the calcilytic compound NPS 2143" if you ever publish a paper were you have used it

Please email Associate Professor Daniel Sejer Pedersen at daniel.pedersen@sund.ku.dk if you are interested.

NPS2143 is by no means the only interesting compound we have sitting on the shelf and if this turns out to be a success we will definitely offer more free compounds. Let's see what happens. D!

Friday, August 09, 2013

Faking it - Elemental Analysis!

Earlier this year I was refereeing a rather good paper and had I not taken the time to inspect the experimental section I would have accepted it with minor corrections. However, whoever wrote the experimental had clearly never run an elemental analysis before and was hopeless at making them up. The numbers were simply to good and although everything else looked great I had to reject the paper due to serious misconduct/fraud. This made me think that there must be thousands of papers out there with made up elemental and HRMS analyses  as these are really simple to make up. Have a look at this web page for inspiration for realistic elemental data: http://internal.eps.hw.ac.uk/services/analytical/chn-league.htm
After this incident I always read the experimental section first and check the spectra and I really wish that my refereeing colleagues would do the same. The crap you find in the experimental section of all journals including the most prestigious ones is simply unbelievable. Even when the experimental stuff looks great it is remarkable how many procedures we are completely unable to reproduce in our lab.
Anyway, not all hustlers are equally talented as a good friend of mine pointed out yesterday when he sent me this interesting paper by Reto Dorta and co-workers: http://pubs.acs.org/doi/abs/10.1021/om4000067
My friend simply wrote check out supplementary information page 12. And so I did and this is what I found (click on image to enlarge):

Many thanks to Reto Dorta and co-workers for this excellent example of what I guess must be classified as attempted fraud since the fake elemental analysis was never added. D!  

Monday, January 07, 2013

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!

Tuesday, December 11, 2012

Curly Arrow - Established 18th October 2006

So I missed my blog birthday again this year! As usual the stats for the past year at Curly Arrow follows below. Thanks to all the blog followers and everyone else who is using the blog. I wish I had more time to post stuff here but running my university research is very time consuming. When I finally get home I really need to do something that isn't chemistry to avoid going insane.
However, the many posts from over the years and the many very valuable comments by the visitors makes this a great resource and forum for exchange of knowledge for students and more experienced chemists. It really is amazing how may people make it here every day in the search for tips and tricks. Merry Christmas and Happy New Year to those of you that are into that stuff, D!

From 18th October 2011 to 18th October 2012:
Absolute unique visitors: 40,669
Total visits: 57,222 (157 visits/day)
Pageviews: 84,446
Average time on site: 2:27 min
The 10 most frequent visitors identifiable:
(1) Oxford University
(2) Princeton University
(3) Universite de Liege
(4) University of California San Diego
(5) University of Cambridge
(6) Imperial College London
(7) Universidade de Sao Paulo
(8) University of Wisconsin Madison
(9) Stanford University
(10) University of Hull
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Top 10 countries that visit the blog:
(1) United States
(2) United Kingdom
(3) Germany
(4) India
(5) Canada
(6) Australia
(7) Denmark
(8) Japan
(9) France
(10) South Korea
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D!