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Pictet-Spengler Route to (R)-PZQ
Communityschisto research community
The Pictet-Spengler reaction is used in the current industrial synthesis of rac-PZQ, and these reactions have been looked at on the Synaptic Leap here.
The PS has been used in the synthesis of PZQ, and we used it as the final step in our solid phase synthesis of PZQ, but both these syntheses were racemic.
General aim is this:
We have now started an Electronic Lab Notebook for the raw data for this specific aspect of the project here. Comments can be left here or there.
Essentially we need to start with literature catalysts for the catalytic, asymmetric Pictet-Spengler reaction. We therefore need to assemble a list of these catalysts here (literature help needed from anyone please!):
2010 Wu et al.
Need more candidate catalysts!
We are looking for people to help screen known catalysts for the relevant reaction. If your lab has any such catalysts we can send you starting material to screen. Substantial contributors to the project will be invited to be authors on the resulting papers.
Log of labs contacted for help with screening: (Important note: declining a request to participate will never be criticised - people may have very valid reasons for not wanting to participate, or may just be too busy. This log is here purely for record, to stimulate readers to suggest alternative/additional collaborating labs, and to avoid duplication of effort. If you know of a lab working on the asymmetric Pictet-Spengler reaction please feel free to contact them and leave a note of the request here.)
Wayne Best of Epichem has suggested an alternative approach based on a PS reaction of a chiral phenylethanolamine. This is an interesting idea, since 1 to 2 (below) might work well with asymmetric induction, and the products resemble PZQ. The use of a chiral starting material, in the generation of some analogue of PZQ that contains an extra stereocentre, could be an interesting project, but it's not clear these analogs would be active. Anyone have a suggestion for a suitable commercially-available chiral starting material? Anyone want to try this?
A chiral auxiliary-mediated PS was reported by Ma et al. (J. Chem. Res. 2004, 2004, 186-187 - paper doesn't seem to have a DOI?) where the key asymmetric step is shown below.
Other examples: Comins 1991
The use of an auxiliary is of course atom-inefficient, however, and likely to be expensive.