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- Wakchaure, Prasad B., et al.
(författare)
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Synthesis of enantiopure angiotensin II type 2 receptor [AT(2)R] antagonist EMA401
- 2015
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 71:38, s. 6881-6887
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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