A Practical Synthesis of Renin Inhibitor MK-1597 (ACT-178882) via Catalytic Enantioselective Hydrogenation and Epimerization of Piperidine Intermediate
2011-02-18T00:00:00Z (GMT) by
A practical enantioselective synthesis of renin inhibitor <b>MK-1597</b> (ACT-178882), a potential new treatment for hypertension, is described. The synthetic route provided <b>MK-1597</b> in nine steps and 29% overall yield from commercially available <i>p</i>-cresol (<b>7</b>). The key features of this sequence include a catalytic asymmetric hydrogenation of a tetrasubstituted ene−ester, a highly efficient epimerization/saponification sequence of <b>4</b> which sets both stereocenters of the molecule, and a short synthesis of amine fragment <b>2</b>.