Chirospecific synthesis of spirocyclic beta-lactams and their characterization as potent type II beta-turn inducing peptide mimetics.
[reaction: see text] Starting from natural proline, a practical chirospecific synthesis of spirocyclic beta-lactams of type 2 is described when a methylene moiety showing minimal steric demand is employed as a constraint element for adjusting the dihedral angle psi(i + 1). Employing the concept of self-reproduction of chirality, C-formylation of the oxazolidinone 5 afforded the key intermediate 7 taking advantage of an intermediate protection of the bridging element as a vinyl moiety. NMR- and IR-based conformational studies clearly indicated that spiro-beta-lactams of type 2 can serve as efficient beta-turn nucleators.
Bittermann
Holger
H
Department of Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
Gmeiner
Peter
P
D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D047090:beta-Lactams / Q000138:chemical synthesis / Q000737:chemistry*
D010455:Peptides; D047090:beta-Lactams