- Reduction of an enaminone: Synthesis of the diamino alcohol core of ritonavir
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The reduction of (5S)-2-amino-5-dibenzylamino-4-oxo-l,6-diphenylhex-2-ene was optimized for diastereoselectivity and overall conversion to (2S,3S,5S)-5-amino-2-dibenzylamino-3-hydroxy-l,6-diphenylhexane (2a). A two-step reduction sequence is described wherein the enamine is reduced with a borane-sulfonate derivative followed by reduction of the resulting ketone with sodium borohydride. The desired 2a was obtained with 84% diastereoselectivity and an acyclic 1,4 stereoinduction ratio of 14:1. This methodology has been used to produce multikilogram quantities of the diamino alcohol core, of Ritonavir and should be general to the synthesis of related diamino hydroxyethylene isosteres.
- Haight, Anthony R.,Stuk, Timothy L.,Allen, Michael S.,Bhagavatula, Lakshmi,Fitzgerald, Michael,Hannick, Steven M.,Kerdesky, Francis A.J.,Menzia, Jerome A.,Parekh, Shyamal I.,Robbins, Timothy A.,Scarpetti, David,Tien, Jien-Heh J.
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