Triflic Acid Catalysed PS Reactions

28 Feb
Published by KatB

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). Interestingly, the yield increased as the acid loading was reduced.
The conditions were mostly optimised before the experiment was run with PZQ and the 3 analogues at 10 and 5% catalyst loadings. The non-dimethoxy peptide acetals (PZQ and the N-benzoyl PZQ analogue) did not go to completion.* 

I'm still in the process of recrystallising and/or attempting to purify the products so the experiments and summary are incomplete (as of 28/02/12).
 
10 mol% TfOH catalysed PS reactions

  • The dimethoxy N-benzoyl PZQ analogue (KAB8-12).
  • The dimethoxy PZQ analogue (KAB1-4).
  • The N-benzoyl PZQ analogue (KAB7-3).
  • PZQ (KAB3-17).

 5 mol% TfOH catalysed PS reactions

 Yield Summary
I'm still attempting to re-crystallise the praziquantel enamide and the dimethoxy PZQ analogue. The table below will be updated as soon as those procedures are complete.

 
 
*Previous attempts to catalytically produce PZQ under various TfOH loadings (60-5%) gave the enediamide intermediate (KAB3-11KAB3-12 to KAB3-16KAB3-17). Increasing the temperature or catalyst loading only decreased the time to give the intermediate, before the contents of the reaction mixture decomposed.