Synthesis of Enantiomerically Pure Amino Acids Containing 2,5-Disubstituted THF Rings in the Molecular Backbone

N- and C-protected derivatives of 2,5-disubstituted trans- and cis-THF amino acids 6 and 7 were prepared in enantiomerically pure form from L-alanine. Felkin–Anh-controlled reduction of the ketone 9 was achieved with a 85:15 diastereoselectivity. Epoxidation of 10 and subsequent intramolecular epoxide opening gave the trans- and cis-THF alcohols 11 and 12, which were further transformed into the corresponding N- and C-protected 2,5-disubstituted trans- and cis-THF amino acids. Conformational studies show that the cis-THF diamide 34 is a β-turn mimetic in the solid state and in CDCl3 solution.