Update:- January 2012

20 Jan
Published by m.robertson

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 PZQ analogues shown below (compounds 6-8) via the Pictet-Spengler cyclization of the relevant Ugi products.  These samples are now ready for screening, please contact us if you would like to help.

As our ultimate goal is to find a catalytic, asymmetric PS route to PZQ and its derivatives we started looking at firstly catalytic PS reactions using methane sulfonic acid.  After we showed that we could get this to work we then went onto looking for Bronsted acids that would catalyse the reaction.  Looking back at previous data it looked like Bronsted acid 9 showed promising signs.  Working on the electron rich systems (3 and 4) we observed (by LCMS) what looked like product as well as intermediate enediamide (10) being formed in a clean reaction.

We are currently working to optimise this reaction with the goal of trying the enantiopure versions of 9 in an attempt to show some enantioselectivity.  Once we show this we'd then like to appeal to other research groups out there with experience in this field to help us with catalyst screening, selection and optimisation.  Again, if you think you can help or would like to get involved please contact us.  We can supply pre-cyclization compounds, experimental procedures and analytical data.

As a result of this work we have also started to put together a review on the catalytic, asymmetric Pictet-Spengler reaction.  The construction of this is in the open on a wiki page and we are encouraging anybody to contribute to it.  This is a novel concept in the chemistry world but should result in a citable article where contributors will be credited for their work by joint authorship.