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Synfacts 2010(7): 0735-0735
DOI: 10.1055/s-0029-1220014
DOI: 10.1055/s-0029-1220014
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag
Stuttgart ˙ New York
Synthesis of Aliskiren
Contributor(s):Philip KocienskiS. Hanessian*, S. Guesné, E. Chénard
Université de Montréal, Canada
Total Synthesis of ‘Aliskiren’: The First Renin Inhibitor in Clinical Practice for Hypertension
Org. Lett. 2010, 12: 1816-1819
Université de Montréal, Canada
Total Synthesis of ‘Aliskiren’: The First Renin Inhibitor in Clinical Practice for Hypertension
Org. Lett. 2010, 12: 1816-1819
Further Information
Publication History
Publication Date:
22 June 2010 (online)
Key words
aliskiren - ring-closing metathesis - macrocyclization - Du Bois aziridination
Significance
Aliskiren is a novel renin inhibitor that is prescribed for the treatment of hypertension. This short and elegant synthesis features the construction of a nine-membered ring by ring-closing metathesis to give B followed by an acid-catalyzed rearrangement of the aziridine C to give pyrrolidine D in 81% yield.
Comment
The diene A was an 8:1 mixture of diastereoisomers. The minor (syn) isomer failed to undergo ring-closing metathesis. The rearrangement C → D probably involves the initial generation of a benzylic carbocation stabilized by the ;4-methoxyphenyl group.