The Synaptic Leap

 I have just packaged up TCMDC-123794 (PMY 11-2) and -123812 (PMY 10-2) along with the parent acid (PMY 8-2), ester (PMY 6-1), aldehyde (PMY 2-4), near neighbour analogue (PMY 14-1) and also the acylurea by-product (PMY 12-1-A). These have been sent to GSK Tres Cantos where the original study was carried out for further testing.

I'm now happy with the data for TCMDC-123812 and TCMDC-123794. A bit of usual practical annoynce with TCMDC-123794 caused some trivial issues, namely a bit of repurification and acetone in the final spectra. These have now been taken care of and the compounds are ready for testing!
I've summarised the various intermediates and other compounds that are in the works on OpenWetWare. Please get in touch if you're interested in testing them.

I'm now fairly confident that I've made TCMDC-123794 and TCMDC-123812. By fairly confident I mean that I've got a reasonable looking but crude 1H NMR and low res. mass spec of both of the compounds. They are not clean by NMR after a column and the yield of the reaction was pretty bad (~20%). Still this isn't too bad for a first go, using a quick and dirty acid chloride. Most of the mass seems to go toward turning the acid into the anhydride. This is supported by NMR but mass spec hasn't given a positive result so far.

This is a post of random synthesis ideas for praziquantel that have been sitting in my inbox for too long. Both sources are industrial. If anyone has any comments, please post. If anyone has any further ideas, please post directly here – you can see how long it can take things to emerge if you use email...
 

 I came upon this reference:
http://www3.interscience.wiley.com/journal/123349682/abstract
which refers to masking of bitter taste of an API through formulation with a beta-cyclodextrin derivative.

Based on past experience with "Chiral Switch" projects in a commercial environment, I have drafted the attached document as a summary of my understanding of the aims of the PZQ project in the context of what would be needed (technically) to get (R)-PZQ to market in the western world.  This does not examine manufacture per se, but rather the many necessary steps to obtain permission to market.  I am sure there are some which I may have missed, but the point is that there would (in my past experience) be far more going on than focussing as at present on "manufacture" and "cost of goods", however important these will be in the long-run. 

Let's think long-term: How best to scale up production of PZQ?

This is likely most economically done in India or China (possibly Brazil or South Africa), all of which have well-established pharmaceutical manufacturing sectors.  However, building manufacturing capacity in poorer disease-endemic countries stands to have enormous benefits for economic development and potential to eventually better meet local and regional general pharmaceutical demand! 

Project to determine if it is feasible to automate / accelerate the catalyst screening project through automated software systems. 
Currently the project is in requirements initiation. We are defining top level requirements of what an automated tool will look like.  Please feel free to contribute

I'd like to suggest that this approach deserves its own thread - at present it is mentioned within the stereoselective synthesis project.  I think it is more important than that - if you agree, there is existing content that should be migrated across to here.