Synthesis and NMR Studies of Activated Derivatives ofcis- andtrans-5-Amino-6-oxopiperidine-2-carboxylic Acid and the Corresponding Bicyclic Dilactam 2,5-DBO: Potential Building Blocks for Stereoregular Polyamides and Peptides

Abstract

Presented here are the syntheses of bicyclodilactams as precursors of polymeric lactams. A new preparation for the 2,5-diazabicyclo[2.2.2]octa-3,6-dione was developed. The four possible dimers were prepared from the N-protected cis- and trans-5-amino-6-oxopiperidine-2-carboxylates (Apc's). Base treatment of the trans activated ester led to the polymer. Synthesis of the isomeric 2,6-diazabicyclo[2.2.2]octan-3,5-dione was not successful even under conditions in which substituted compounds were found. From the 1H NMR spectral data for the monomers and dimers, we concluded that the H−H coupling constants for the cis- and trans-Apc monomers are consistent with the low-energy pseudo-chair conformations inferred from structures optimized at the B3PW91/6-31G* level of density functional theory. The two-dimensional NMR spectra of the oligomers give no evidence for β-turn formation in DMSO-d 6.

An Access to Aza-Freidinger Lactams and E-Locked Analogs

“…The formal exchange of C α H i+ 1 by N results in Z -configured aza-Freidinger lactams ( 2 ). A linkage from C α H i to C α H i+ 1 provides the 5-amino-6-oxopiperidine-2-carboxylic acid (Apc) derivatives 3 with a constrained E configuration, and an analogous exchange of C α H i+ 1 by N yields the corresponding azapeptides of type 4 .…”