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 an N-protected 3,6-bis[4-aminoalkyl]-2,5-diketopiperazine comprising heating a solution comprising:
a. an amino acid having a free α-amine group and a protected amine group, and
b. means for catalyzing dehydrative cyclocondensation of said amino acid;
c. wherein said solution is heated to a target temperature between 160° C. and 170° C., and the target temperature is achieved in 4-6 hours and said target temperature is maintained for up to 8 hours.
2. The method of claim 1 , wherein said target temperature is maintained for up to 6 hours.
3. The method of claim 1 , wherein said synthesis is-complete within 8 hours of reaching said target temperature.
4. The method of claim 1 , wherein said means for catalyzing dehydrative cyclocondensation of said amino acid comprises addition of a catalyst to the solution, wherein said catalyst comprises at least one of sulfuric acid, phosphoric acid, or phosphorus pentoxide.
5. The method of claim 1 , wherein the solution further comprises m-cresol, ethylene glycol, propylene glycol, toluene, or xylene.
6. A method for the synthesis of N-protected 3,6-bis[4-aminoalkyl]-2,5-diketopiperazine comprising:
a. a step for catalyzing a dehydrative cyclocondensation reaction of an amino acid having a free α-amine group and a protected amine group, and
b. collecting the N-protected 3,6-bis[4-aminoalkyl]-2,5-diketopiperazine on a filter;
c. wherein said dehydrative cyclocondensation reaction comprises heating to a target temperature between 160° C. and 170° C. and the target temperature is achieved in 4-6 hours and said target temperature is maintained for up to 8 hours.
7. The method of claim 6 , wherein said-target temperature is maintained for up to 6 hours.
8. The method of claim 6 , wherein said synthesis is complete within 8 hours of reaching said target temperature.
9. The method of claim 6 , wherein said step for catalyzing dehydrative cyclocondensation of said amino acid comprises using at least one of sulfuric acid, phosphoric acid, or phosphorus pentoxide as the catalyst.
10. A method for the synthesis of N-protected 3,6-bis[4-aminoalkyl]-2,5-diketopiperazine comprising: a. adding an amino acid having a free α-amine group and a protected amine group to a solvent, and b. a step for catalyzing dehydrative cyclocondensation of the amino acid having a free α-amine group and a protected amine group, wherein said step for catalyzing comprises heating said solvent containing said amino acid to a target temperature between 160° C. and 170° C. and the target temperature is achieved in 4-6 hours and said target temperature is maintained for up to 8 hours.
11. The method of claim 10 , wherein said target temperature is maintained for up to 6 hours.
12. The method of claim 10 , wherein said synthesis is-complete within about 8 hours of reaching said target temperature.
13. The method of claim 10 , wherein said step for catalyzing dehydrative cyclocondensation of said amino acid comprises addition of a catalyst to the solution, wherein said catalyst comprises at least one of sulfuric acid, phosphoric acid, or phosphorus pentoxide.