…..within february and march 2012 I really got very close to the total synthesis of my target molecule. I had to run through three synthetic strategies regarding the last steps. Changing the functional groups implemented in the precursor should give me the final product. Unfortunately it was not possible to isolate the natural product in the end, although I could already detect the molecular mass in LC-MS and HRMS-ESI already. I had a crude product mixture in hands which I could not purify neither by simple column chromatography nor by more advanced HPL-Chromatography. On the other hand my results are valuable as I could develop a dependable strategy to build up necessary precursors.
Hopefully at some point people will make use of my laboratory experience and my results so far. In my opinion the synthetic strategy I was following is superior to other strategies I found so far. With my reactions I can more or less easily provdide precursors in a convergent fashion.
What my synthesis was about, I will tell you in some more detailed posts.
Stay tuned 🙂
I just read a very nice peace of work regarding malaria-treatment. This inspires me to show three very nice publications to you, which I discovered in the last feew weeks. Three of them are very impressive papers, the scientific results could give malaria treatment a push. As it is not longer a secret that malaria resistance against artemisinin was discovered at the cambodian border, it is very important to elaborate new affordable drugs or to improve old ones.
But as you can read in these articles (or at least in the abstracts) there are three promising things in the pipeline.
Malaria-infeted mice are completely cured
It describes that mice can be cured completely by artemisinin-based derivatives, the so called anilides, in combination with mefloquine. Anilides still bear a trioxane unit which is the active group in artemisinin but are further decorated with some sulfur-containing groups. These derivatives can easily be obtained by simple chemical manipulations of dihydroartemisinin and show remarkable activity against Plasmodium berghei.
Production of the antimalarial drug precursor artemisinic acid in engineered yeast
This very interesting and trendsetting paper describes the production of artemisinic acid in genetically changed yeast. By that you can develope a very efficient way to provide infected people with artemisinin. It is just neccessary to further modify the obtained compound by two oxidation steps to get the desired antimalarial agent.
You could have asked now….ok, there is a cheap and efficient way to produce artemisinic acid and the two steps to yield artemisinin out of this acid are very straightforward as well. But why there is no application to supply people with this drug? Especially if you consider that the price for natural artemisinin fluctuates heavily as it depends on good harvests of the plant Artemisia annua. Listen up, here comes the answer!
Continuous-flow synthesis of the anti-malaria drug artemisinin
Seeberger and colleagues reported about a very efficient way to achieve the last synthetic steps in large scale reactions. They are using a selfbuilt flow-reactor to manage this conversions and end up with a good yield of this important drug. They claym that it is possible to produce 200g of artemisinin within one day and 1500 reactors would be enough to cover the global need for this drug. I really think that this is a promissing technique to produce affordable artemisinin-based therapeutics. But this achivement is just successful if the people do not longer stick to artemisinin monotherapies as this enforces the resistance of plasmodium towards this drug.
Stay tuned 😉
Today I did it!
The hydrolysis of a very stable diethyl-acetal with 2M hydrogenchloride worked (THF, 2 h, reflux) and the following intramolecular cyclisation of a beta-ketoamide with the now deprotected aldehyde worked as well. LC-MS reactioncontroll is a really helpfull tool to get quick information about a conversion. I proceeded to check wether the compund is TLC stable or not by simple 2D-TLC. Yes! It is! Quickly ran a column with HRMS-analysis of the collected Spot. Perfect! It´s a mixture of three compounds with nearly the same Rf-value ! The cyclised compound, the cyclised compound including elimination of the newly formed alcohol and traces of my final compound! Tomorrow I will give sodiumhydroxide another chance to give me the cyclised and eliminated compound. Then it is just one step away from the total synthesis of…..
I just want you to participate in this progress and I want to show, how emotional chemistry can be. More details regarding the synthesis strategy and the final product will follow as soon as possible.
Stay tuned 😉
Als Organischer Chemiker in der Totalsynthese hat man es manchmal wirklich nicht leicht. Besonders Schlüsselschritte machen mir ab und an dann doch mal Kopfschmerzen, aber irgendwie schafft man es dann doch! Frei nach dem Motto: Wer kämpft, kann verlieren. Wer nicht kämpft, hat schon verloren (Bertolt Brecht, wenn ich mich nicht täusche?) Heute hätte ich aber noch so sehr kämpfen können, ohne Laborumluft kann man aber leider nicht arbeiten, so sehr es mir auch in den Fingern gejuckt hat!
Jedenfalls sieht es insgesamt sehr guuut aus
… Three steps away from the Total Synthesis of…..
Ich halte Euch auf dem Laufenden!
Stay tuned 😉