Synthesis of the potential dipeptide neuroleptic dilept and its active metabolite

• DOI: 10.1007/s11094-013-0937-y
• Publication Date: 2013-10-19T01:23:27Z
• Authors: E. A. Kuznetsova; N. M. Sazonova; S. V. Nikitin; L. A. Zhmurenko; T. A. Gudasheva
• Keywords: 0301 basic medicine; 03 medical and health sciences; 01 natural sciences; 0104 chemical sciences

The new potential neuroleptic drug dilept (N-caproyl-L-prolyl-L-tyrosine methyl ester) was created. A four-step scalable synthetic method for dilept that enabled the product to be obtained in 52% yield without racemization was presented. The process included preparation of caproic acid chloride using thionylchloride, Schotten–Baumann acylation of L-proline by the obtained acid chloride, esterification of L-tyrosine in MeOH in the presence of thionylchloride, and synthesis of the methyl ester of N-caproyl-L-prolyl-L-tyrosine by the mixed anhydride method using isobutylchloroformate in DMF. The active metabolite of dilept (N-caproyl-L-prolyl-L-tyrosine) was synthesized and characterized by physicochemical methods.