Catalysis of diketopiperazine synthesis
View Patent ↗Provided is a method for the synthesis of N-protected bis-3,6-[4-aminobutyl]-2,5-diketopiperazine including the step of heating a solution of ε-amino protected lysine in the presence of a catalyst selected from the group consisting of sulfuric acid, phosphoric acid, and phosphorus pentoxide.
1. A method for the synthesis of N-protected bis-3,6-[3-aminopropyl]-2,5-diketopiperazine comprising the step of heating a solution of N-benzyloxycarbonyl-ornithine in the presence of a catalyst selected from the group consisting of sulfuric acid, phosphoric acid, and phosphorus pentoxide, wherein said synthesis has a yield of greater than about 50%.
2. The method of claim 1 , wherein said catalyst is phosphorous pentoxide.
3. The method of claim 2 , wherein the concentration of phosphorus pentoxide is from about 5% to about 10%.
4. The method of claim 3 , wherein the concentration of phosphorus pentoxide is about 7.5%.
5. The method of claim 1 , wherein the solution comprises m-cresol, ethylene glycol, propylene glycol, toluene, or xylene.
6. The method of claim 1 , wherein the solution is heated to a target temperature of about 160° C. to 170° C.
7. The method of claim 1 , wherein said catalyst is sulfuric acid.
8. The method of claim 1 , wherein said catalyst is phosphoric acid.
9. The method of claim 6 , wherein the solution is held at the target temperature for up to 2 hours.
10. The method of claim 6 , wherein the solution is held at the target temperature for up to 4 hours.
11. The method of claim 6 , wherein the solution is held at the target temperature for up to 6 hours.
12. The method of claim 1 wherein said synthesis has a yield of about 55%.
13. The method of claim 1 wherein said synthesis has a yield of about 60%.