Synthesis of enantiopure angiotensin II type 2 receptor [AT(2)R] antagonist EMA401
2015 (English)In: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 71, no 38, 6881-6887 p.Article in journal (Refereed) Published
We report a facile synthesis of the angiotensin II type 2 receptor antagonist EMA401, which recently passed phase II clinical trials, in high overall yield. The synthesis of the key phenylalanine intermediate involved the formation of an a-nitro cinnamic ester and its reduction followed by a Pictet-Spengler cyclization, which furnished the tetrahydroisoquinoline core structure. Next, EMA401 was separated from its enantiomer EMA402 by four recrystalizations of a diastereomeric salt in 98% ee. All steps were performed on gram scale with emphasis on avoiding column purification and using readily available low cost starting materials and reagents.
Place, publisher, year, edition, pages
2015. Vol. 71, no 38, 6881-6887 p.
EMA401, Angiotensin II type 2 receptor, Synthesis, Enantiopure
IdentifiersURN: urn:nbn:se:uu:diva-262404DOI: 10.1016/j.tet.2015.07.018ISI: 000359874300032OAI: oai:DiVA.org:uu-262404DiVA: diva2:855439