First Full Paper on a TSL Project

21 Sep
Published by MatTodd



The first paper arising from the open science coordinated by this site has just been published here. Though the project is very much ongoing, it's super exciting to be able to publish a paper as a milestone. i.e. one can run an open project, and once a certain point has been reached, one can submit a paper for traditional peer review to act as a reviewed summary of progress.
Many people are thanked in the original article, but I'd like to say thank you to everyone who helped the project on this site, particularly you industry/process guys - your advice was readily forthcoming and of a particularly high quality.
A key message of the paper I think is that the research occurred faster because it was open source - i.e. not just that the data were freely available, but that anyone could input into the direction of the project at any level as it was taking place. This is a simple (and seemingly trivial) expedient, but one that has important implications for how we could/should be doing science in the future. I hope that people find this kind of interactivity and transparency motivating, and I hope that we can continue to use this new way of doing things to solve more problems, and quickly.


..for getting the paper out.
As an aside, it has been confirmed to us that the Merck process is used extensively (we were told "exclusively"), but the initial reduction product is usually taken on crude to the cyclic material which is then sold on to the PZQ manufacturers. This is why we have had difficulty in sourcing this intermediate for the resolution. 

MatTodd's picture

Thanks Bill.
You don't have a citable source for that Merck fact, do you? We've another way of making that material, and are guessing at how much the Merck process is used, sadly. Aiming to publish as soon as I find the time to write it up.

We were informed about this by one of the main manufacturers of PZQ who purchases the cyclised benzoyl intermediate (from China). He is trying to see if they can tap some of the solution off for us prior to cyclisation! Hopefully he has somewhat more clout than us.
As mentioned previously, we were not able to purchase this (though I can show you 2 contracts from 2 different Chinese "suppliers" who took the money and never sent anything!) and I had to make it by a circuitous route; Reissert product, air/caustic/PTC to give 1-cyanoisoquinoline, hydrogenation to the amine (very clean), benzoylation, hydrogenation, CBZ formation (to remove from the undesired hydrogenation product as the benzene ring also goes) and chromatography, hydrogenolysis..................