title: Analogues of key precursors of aspartyl protease inhibitors: synthesis of trifluoromethyl amino epoxides.
abstract: The synthesis of the title compound is described through original and tailored synthetic protocols. The addition of vinylmagnesium bromide to CF(3)-N-aryl and N-alkyl aldimines was efficient and did not require an activating N-substituent. The resultant CF3-allylamines were converted in an efficient and completely stereoselective route to syn CF3-epoxides 3 via formation of bromhydrins 8. The same sequence performed from the aldimine substituted with the methyl ether of the (R)-phenylglycinol provided the homochiral (R,R)-amino epoxide (de >98%). This study has allowed access to the novel racemic and homochiral trifluoromethyl beta-amino epoxides, analogues of key precursors of various HIV protease inhibitors.
authors.affiliation: BioCIS-CNRS, Centre d'Etudes Pharmaceutiques, rue J.B. Clément, Châtenay-Malabry 92296 Cedex, France.
authors.forename: Nguyen Thi Ngoc
authors.initials: NT
authors.lastname: Tam
authors.forename: Guillaume
authors.initials: G
authors.lastname: Magueur
authors.forename: Michèle
authors.initials: M
authors.lastname: Ourévitch
authors.forename: Benoit
authors.initials: B
authors.lastname: Crousse
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bégué
authors.forename: Danièle
authors.initials: D
authors.lastname: Bonnet-Delpon
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000588:Amines; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D011355:Prodrugs; D016282:Aspartic Acid Endopeptidases