Analogues of key precursors of aspartyl protease inhibitors: synthesis of trifluoromethyl amino epoxides.
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.
Tam
Nguyen Thi Ngoc
NT
BioCIS-CNRS, Centre d'Etudes Pharmaceutiques, rue J.B. Clément, Châtenay-Malabry 92296 Cedex, France.
Magueur
Guillaume
G
Ourévitch
Michèle
M
Crousse
Benoit
B
Bégué
Jean-Pierre
JP
Bonnet-Delpon
Danièle
D
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
D000588:Amines; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D011355:Prodrugs; D016282:Aspartic Acid Endopeptidases