A new convenient synthesis of 2-trifluoromethyl substituted aspartic acid and its isopeptides. Part 11

Abstract

The reaction of methyl 2-benzyloxycarbonylimino-3,3,3-trifluoropropionate with acetylchloride–triethyI-amine yields methyl 2-benzyloxy-6-oxo-4,5-dihydro-4-trifluoromethyl-1,3-oxazine-4-carboxylate, a β-activated equivalent for 2-trifluoromethyl substituted aspartic acid. This reagent offers a versatile route to β-derivatized 2-trifluoromethyl substituted aspartic esters via nucleophilic ring cleavage; with amino acid esters isoaspartyl peptides are formed. The diastereoisomeric dipeptides have been separated by flash chromatography; for benzyl N-benzyloxycarbonyl-R-2-trifluoromethyl-β-aspartyl-(α-methylester)-S-prolinate an X-ray analysis is presented. Benzyl N-benzyloxycarbonyl-S-2-trifluoro-methyl-β-aspartyl-(α-methylester)-S-prolinate exists as a mixture of cis–trans conformers in solution at room temperature.