Racemic N-sulfonyloxaziridines as highly diastereoselective enolate hydroxylating agents: enantioselective synthesis of (2S,3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide |
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Authors: | Eleonóra KissIstván E Markó Michel Guillaume |
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Institution: | a Université catholique de Louvain, Bâtiment Lavoisier, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium b Johnson & Johnson Pharmaceutical Research and Development, Chemical Process Research, Turnhoutseweg 30, B-2340 Beerse, Belgium |
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Abstract: | A new, highly enantioselective synthesis of (2S,3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide, a synthetic fragment of the experimental hepatitis C drug Telaprevir, has been described. Conjugate addition of the enantiomerically pure Davies lithium amide followed by hydroxylation of the in situ generated β-amino enolate was employed for the formation of the required stereogenic centres. Importantly, very high diastereoselectivities can still be achieved in the key-step when the relatively expensive and enantiopure (camphorsulfonyl)oxaziridine hydroxylating agent is replaced by racemic trans-N-sulfonyloxaziridines. Among the tested N-sulfonyloxaziridines the iso-propyl substituted analogue proved to be the ideal choice from an economic viewpoint. |
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Keywords: | Diastereoselective hydroxylation Enolate hydroxylation N-Sulfonyloxaziridines Telaprevir Diastereoselective Michael |
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