A stereoselective catalytic nitroaldol reaction as key step in a novel strategy for the synthesis of the renin inhibitor Aliskiren
Articolo
Data di Pubblicazione:
2015
Citazione:
A stereoselective catalytic nitroaldol reaction as key step in a novel strategy for the synthesis of the renin inhibitor Aliskiren / S. Rossi, M. Benaglia, R. Porta, L. Cotarca, P. Maragni, M. Verzini. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1099-0690. - :11(2015 Apr), pp. 2531-2537. [10.1002/ejoc.201403659]
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 A(1)), 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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Drug design; Synthetic methods; Asymmetric synthesis; Diastereoselectivity; Medicinal chemistry; Nitro compounds; Henry reaction
Elenco autori:
S. Rossi, M. Benaglia, R. Porta, L. Cotarca, P. Maragni, M. Verzini
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