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- Title
A Stereoselective Catalytic Nitroaldol Reaction as the Key Step in a Strategy for the Synthesis of the Renin Inhibitor Aliskiren.
- Authors
Rossi, Sergio; Benaglia, Maurizio; Porta, Riccardo; Cotarca, Livius; Maragni, Paolo; Verzini, Massimo
- Abstract
Aliskiren is the first-in-class orally active direct renin inhibitor. It was approved in 2007 for the treatment of hypertension. We have designed a new strategy for the convergent synthesis of aliskiren that involves a catalytic stereoselective nitroaldol reaction as the key step. A new enantiopure nitroalkane (synthon A1), prepared in only three steps from a commercially available enantiopure 2-(arylmethyl)-3-methyl butanol derivative, was successfully used in a copper-catalysed Henry reaction to give a nitrolactone intermediate in which the correct configuration for the final product was established at all four stereocentres. Nitro-group reduction, Boc-protection of the resulting amine, aminolysis of the lactone with 3-amino-2,2-dimethylpropionamide, and finally Boc-deprotection led to the enantiopure renin inhibitor aliskiren.
- Subjects
ALISKIREN; CHEMICAL synthesis; STEREOSELECTIVE reactions; NITROALDOL reactions; NITROALKENES; CHEMICAL derivatives; LACTONES; CHEMICAL reduction; RENIN inhibitors
- Publication
European Journal of Organic Chemistry, 2015, Vol 2015, Issue 11, p2531
- ISSN
1434-193X
- Publication type
Article
- DOI
10.1002/ejoc.201403659