A general approach to dehydro-Freidinger lactams: ex-chiral pool synthesis and spectroscopic evaluation as potential reverse turn inducers.
Starting from natural alpha-amino acids, a practical synthesis of the dehydro-Freidinger lactams 9a-h based on the ring-closing olefin metathesis reaction was investigated. The presented examples comprise 6-, 7-, 8-, 9-, and 10-membered cyclic dipeptide mimics. Structural variations were demonstrated. We approached the metathesis precursors 8a-h employing an N-alkylation/peptide-coupling strategy. Subsequent ring closure was promoted by the ruthenium-based catalyst 10a or 10b. The resulting tetraresidue 11d was shown to undergo intramolecular hydrogen bonding based on NMR and FT-IR studies. Thus, the development of dehydro-Freidinger lactams as potential reverse turn inducers stabilizing an intramolecular NH(i+3)...CO(i) hydrogen-bond was demonstrated.
Hoffmann
Tobias
T
Department of Medicinal Chemistry, Emil Fischer Center, Friedrich-Alexander-University, Schuhstr. 19, D-91052 Erlangen, Germany.
Waibel
Reiner
R
Gmeiner
Peter
P