A novel synthesis of enantiopure hydroxyethylamine isosteres 1 has been developed. Reaction of lithiated β-sulfinylethylamines 3 with N-Cbz-imines generated in situ from α-amino-sulfones 4 afforded in good to excellent yields and moderate stereocontrol the 2-sulfinyl-1,3-diamines 2. The latter were submitted to the nonoxidative Pummerer reaction (NOPR) in CH2Cl 2, that produced the target compounds 1 in very good yields with inversion of configuration. In some cases, the use of acetonitrile as solvent resulted in a double-inversion pathway, leading for example to the oxazolidinone 5. The total synthesis of an epimer of Saquinavir has been achieved by this method.
|Titolo:||Stereocontrolled synthesis of hydroxyethylamine isosteres via chiral sulfoxide chemistry|
|Parole Chiave:||peptidomimetics; sulfoxides; Mannich reaction|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Data di pubblicazione:||21-giu-2004|
|Digital Object Identifier (DOI):||10.1016/j.tetlet.2004.04.160|
|Appare nelle tipologie:||01 - Articolo su periodico|