While this schisto community is not terribly active right now there was just published an excellent open access issue of Future Med Chem, edited by Conor Caffrey, and with articles by many of the major players in the field.
This thread starteded as a place to locate anything related to the final API form(s) in which PZQ might be isolated (ie Drug Substance), or the formulation of these into Drug Product.
Over the next 12 weeks I will be working on a model system for the Lewis Acid catalysed Pictet-Spengler formation of substitued tetrahydroisoquinolines (e.g. 4).
After making the starting materials (3, R1 = H, OMe and R2 = H, NO2, OMe) I'll work on screening various Lewis Acids with a focus on silver(I) triflate, given recent results - see AgOTf post here.
Was alerted to this NCTT project/proposal for deuterated analogs of enantiopure PZQ, with the deuteration being used to slow metabolism. Would be interesting to see how many D's are incorporated, and where (presumably at least the 4' position). I hope they're using our resolution approach to make their enantiopure material. And I wonder what the deuteration does to the cost, on scale?
(original page http://nctt.nih.gov/27545311)
The use of catalytic triflic acid TfOH in the Pictet-Spengler reaction was initially performed as a control for the silver(I) triflate (AgOTf) catalysed reaction (here). All early experiments using TfOH were performed with the dimethoxy N-benzoyl PZQ analogue and catalyst loading was reduced down to 5% (KAB8-7 & KAB8-8, KAB8-9).
It's been too long since I've updated the progress of this project on here but here's a brief summary of where we are and what's planned for the near future. From late November we've had a summer student, Kat Badiola, working on the project. She started with preparing pure, racemic samples of the 3
I was looking at all the difficulty that is occuring with finding a cheap source of chiral catalyst for the Pictet-Splenger and mused about using Phenylglycine, as this avoids the issue due to it being part of the chiral pool.
Anyway here is my attempt at getting the key ring system together for the system. Don't think anything I used is particularly expensive. Sorry about the conditions being vague, was just a quick thought that I came up with.
Background Relevant experiment. Basically, the Pictet-Spengler to form 3 PZQ analogues and PZQ itself.
The mass spec is of a by-product of the acid mediated PS cyclisation of MNR10-1 to form KAB8-1, aka the dimethoxy N-benzoyl PZQ analogue.
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