The Synaptic Leap

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! 

PZQ can’t be resolved as-is (unless anyone has any bright ideas how to resolve amides). One of the most promising strategies to prepare enantiopure praziquantel (using a strategy that starts from the racemate) is a classical resolution of praziquanamine (1, "PZQamine"). This molecule can either be made from scratch (it’s an intermediate in the current PZQ synthesis) or can be obtained in high yield from PZQ itself.
 
 

 
The synthesis of rac-PZQ via the Pictet-Spengler route was developed by the Korean Shin Poong Pharmaceutical Company and obtains very low production costs of US¢7 per 600 mg tablet of the drug.

First step (amide bond formation to give 3)
Second step (attachment of acetal to give 4) - there's also a one-pot procedure to combine the first 2 steps
Third step (cyclization to praziquanamine to give 5)
Fourth step...

Project A: Development of a low-cost enantioselective synthesis of PZQ. It's an open project, like everything on TSL.
Meaning?: contributors can change anything they wish on these pages.
If you wish to contribute: please don't leave comments here. Instead, edit the pages below directly or leave comments.
Other ways to interact: The Friendfeed page and the Lab Book Blog (for the Pictet-Spengler approach)

 
For an inexpensive route to rac-PZQ (and potentially the enantioenriched material), the relevant starting materials (below) are required. While prices may be obtained for these from commercial catalogues, we require realistic prices of these materials on a large (ton) scale to assess whether this approach to PZQ is economically viable. The starting materials are:
 

Reissert route chemicals:

The most obvious, and known, approach to rac-PZQ is using Reissert chemistry.
 
 
This approach has been used in the following publications:

Last Wednesday I began some simple tests to try to find a good solvent for recrystallization, and here's some details and thoughts on what I've found so far.
I started with PZQ from Merck, fresh stuff from the container.  Just to see if any of these would work, I added a few crystals of PZQ to less than or up to 1 mL of the following solvents: acetone, hexanes, EtOAc, ether, and THF.  The only one lacking real solubility was the hexanes.  This was just a simple and not-supposed-to-be-conclusive test to see if it was worth using any of these.  I might come back to them later, but, besides hexanes, I don't think any of these will be terribly useful for me.
 

I am Luogbou-nzu, PhD student at the university of Yaoundé I camerron. I am working on genetic diversity of Schistosoma haematobium from Cameroon.  At this level I have already collected samples from 10 villages in Cameroon. In total, 44 isolates of adults worms (1273 males and 979 females), 99 samples for miracidia and 37 samples for cercariae are available for molecular analysis.It is very important to gain better insight into the biological haracteristics of the human schistosomes species, including their transmission and epidemiological patterns, that is why a detailed understanding of their genetic structure and heterogeneity is vital.

http://www.who.int/tdr/svc/grants/calls/high-throughput-screening

Information from that post has been copied here for your convenience:

WHO-TDR is accepting applications for two fellowship positions for
training in high throughput screening (HTS) as part of its drug
discovery programme against infectious tropical diseases. This one-year
fellowship will support the training of postdoctoral scientists from
Africa who have interest in drug discovery. Applicants must have a PhD
or equivalent in biological or chemical sciences and be currently
affiliated to an institution in Africa, where s/he will return upon
completion of training.