Process for preparing tripeptide containing oleanolic acid and its therapeutic applications thereof

A process for preparing a compound of structure 1 with SEQ ID #1 attached to oleanolic acid comprising the steps of:

• a. Treating Boc-Lys(Cbz)-OH, wherein both the amino groups of L-Lysine is protected, with Benzyl bromide in Acetone and potassium carbonate to get Boc-Lys(Cbz)-OBzl;
• b. Hydrolyzing the Boc-Lys(Cbz)-OBzl from step (a) to obtain H-Lys(Cbz)-OBzl.HCl;
• c. Coupling the H-Lys(Cbz)-OBzl.HCl of step (b) with Boc-Val-OH in the presence of N, N′-Dicyclohexylcarbodiimide, Hydroxy benzotriazole and triethylamine to obtain Boc-Val-Lys(Cbz)-OBzl;
• d. Treating Boc-Val-Lys(Cbz)-OBzl obtained from step c) with trifluoroacetic acid to obtain H-Val-Lys(Cbz)-OBzl;
• e. Coupling H-Val-Lys(Cbz)-OBzl of step d) with Boc-Lys(Cbz)-OH in the presence of N, N′-Dicyclohexylcarbodiimide, Hydroxy benzotriazole and triethylamine to obtain Boc-Lys(Bzl)-Val-Lys (Cbz)-OBzl;
• f. Treating Boc-Lys(Bzl)-Val-Lys(Cbz)-OBzl of step e) with trifluoroacetic acid to obtain H-Lys(Bzl)-Val-Lys(Cbz)-OBzl;
• g. Coupling the H-Lys(Bzl)-Val-Lys(Cbz)-OBzl of above step with 3-O-acetyl Oleanoyl chloride (synthesized from 3-O-acetyl oleanolic acid and thionyl chloride) in the presence of triethylamine to get (3-O-Acetyl Oleanoyl)-Lys(Bzl)-Val-Lys(Cbz)-OBzl;
• h. Hydrogenating the (3-O-Acetyl Oleanoyl)-Lys(Bzl)-Val-Lys(Cbz)-OBzl of step g) in the presence of palladium and carbon catalyst in alcohol medium to get 3-O-Acetyl Oleanoyl-Lys-Val-Lys;
• i. Hydrolyzing the acetyl group using a base in alcohol medium to obtain a tripeptide of SEQ ID #1, linked to oleanolic acid,
• wherein SEQ ID #1 is K-V-K, and structure 1 is represented as below