title: Stereoselective Synthesis of Freidinger Lactams Using Oxaziridines Derived from Amino Acids.
abstract: Conformationally restrained dipeptidyl lactams are building blocks for the synthesis of peptidomimetics, including Freidinger lactams (Figure 1). Few synthetic methodologies toward such moieties allow for incorporation of a stereodefined substituent on the ring nitrogen (i.e., corresponding to an amino acid side chain). Enantiopure Freidinger lactams were obtained by (1) condensation of (S)-tert-butoxycarbonyl (Boc)-protected 2-aminocycloalkanones with commercially available alpha-amino esters, (2) oxidation of the resulting imines with m-CPBA to give spirocyclic oxaziridines, and (3) photorearrangement. Conformational analyses of seven- and eight-membered dipeptidyl lactams by NMR and by X-ray crystallography are described. The utility of this chemistry was illustrated by the synthesis of potential inhibitors of angiotensin converting enzyme (ACE).
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66045-2506.
authors.forename: Michael S.
authors.initials: MS
authors.lastname: Wolfe
authors.forename: Dinah
authors.initials: D
authors.lastname: Dutta
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Aubé