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Synfacts 2011(5): 0461-0461
DOI: 10.1055/s-0030-1259769
DOI: 10.1055/s-0030-1259769
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag
Stuttgart ˙ New York
Synthesis of Renin Inhibitor MK-1597
Rezensent(en):Philip KocienskiC. Molinaro et al.*
Merck, Kirkland, Canada; Merck, Rahway, USA and Actelion Pharmaceuticals, Allschwil, Switzerland
A Practical Synthesis of Renin Inhibitor MK-1597 (ACT-178882) via Catalytic Enantioselective Hydrogenation and Epimerization of Piperidine Intermediate
J. Org. Chem. 2011, 76: 1062-1071
Merck, Kirkland, Canada; Merck, Rahway, USA and Actelion Pharmaceuticals, Allschwil, Switzerland
A Practical Synthesis of Renin Inhibitor MK-1597 (ACT-178882) via Catalytic Enantioselective Hydrogenation and Epimerization of Piperidine Intermediate
J. Org. Chem. 2011, 76: 1062-1071
Weitere Informationen
Publikationsverlauf
Publikationsdatum:
15. April 2011 (online)
Key words
MK-1597 - renin inhibitors - palladium-catalyzed borylation - Suzuki-Miyaura coupling - asymmetric hydrogenation
Significance
The key feature in the synthesis of MK-1597 (ACT-178882) is the highly efficient ruthenium-catalyzed asymmetric hydrogenation of the tetrasubstituted alkene J followed by a mild epimerization reaction to set both stereogenic centers in H (trans/cis > 120:1).
Comment
The renin inhibitor MK-1597 is a promising lead in the treatment of hypertension. It was synthesized in nine steps (longest linear sequence) in 29% overall yield. Most of the intermediates were solids, but they were not purified before being used in the succeeding steps.