Synthesis and stereochemical analysis of β-nitromethane substituted γ-amino acids and peptides

The high diastereoselectivity in the Michael addition of nitromethane to alpha,beta-unsaturated gamma-amino esters, crystal conformations of beta-nitromethane substituted gamma-amino acids and peptides are studied. Results suggest that the N-Boc protected amide NH, conformations of alpha,beta-unsaturated gamma-amino esters and alkyl side chains play a crucial role in dictating the high diastereoselectivity of nitromethane addition to E-vinylogous amino esters. Investigation of the crystal conformations of both alpha,beta-unsaturated gamma-amino esters and the Michael addition products suggests that an H-C-gamma-C-beta=C-alpha eclipsed conformer of the unsaturated amino ester leads to the major (anti) product compared to that of an N-C-gamma-C-beta=C-alpha eclipsed conformer. The major diastereomers were separated and subjected to the peptide synthesis. The single crystal analysis of the dipeptide containing beta-nitromethane substituted gamma-amino acids reveals a helical type of folded conformation with an isolated H-bond involving a nine-atom pseudocycle.