Analogues of Key Precursors of Aspartyl Protease Inhibitors:  Synthesis of Trifluoromethyl Amino Epoxides

• Published in: Journal of organic chemistry 2005-01, Vol.70 (2), p.699-702
• Main Authors: Ngoc Tam, Nguyen Thi, Magueur, Guillaume, Ourévitch, Michèle, Crousse, Benoit, Bégué, Jean-Pierre, Bonnet-Delpon, Danièle
• Format: Article
• Language: English
• Subjects: Amines - chemical synthesis; Amines - chemistry; Amines - pharmacology; Aspartic Acid Endopeptidases - antagonists & inhibitors; Chemistry; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Epoxy Compounds - chemical synthesis; Epoxy Compounds - chemistry; Epoxy Compounds - pharmacology; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Molecular Structure; Organic chemistry; Preparations and properties; Prodrugs - chemical synthesis; Prodrugs - chemistry; Prodrugs - pharmacology; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo0485233

The synthesis of the title compound is described through original and tailored synthetic protocols. The addition of vinylmagnesium bromide to CF3-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 β-amino epoxides, analogues of key precursors of various HIV protease inhibitors.