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Chirospecific synthesis of spirocyclic beta-lactams and their characterization as potent type II beta-turn inducing
Holger Bittermann1, Peter Gmeiner
1Department of Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
Abstract:
[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.
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