Alternative synthesis of PZQ using Phenylglycine

Published by M_Lilley1985 on 12 January 2012 - 11:43am

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.
Alternative synthetic route to PZQ

Comments

MatTodd's picture

Thanks for this. Interesting route, but my gut feeling is that it's too long to be a practical possibility. There are already at least two routes to PZQ that are used on a ton scale, and there is also Doemling's patented Ugi route, and it seems perhaps more promising to start with those and modify, rather than come up with a new route, just because that minimizes R&D costs associated with demonstrating the route works. Unless of course substantial portions of the route you describe are already known and optimized...

 
 Good Attempt, you played with some basic reactions to get to the target. Whetheror not this will solve the problem is a different story. Your time and effort is very much appreciated. Just to refresh my basic chemistry.
*For Friedel-Crafts reaction, i guess you can use your primary alcohol straightaway without converting it into corresponding halide. For more information on FC reactions see this nice review by Rueping (http://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-6-6.pdf)
* Instead of acetly chloride, you can use chloroacetly chloride so that you can avoid one more step.
*For your conversion of primary alcohol to amine you can used NaN3/PPh3 in CCl4-DMF or Mitsunobu/staudinger combination.