Synthesis and conformational studies of peptides from new C-linked carbo-β-amino acids (β-Caas) with anomeric methylamino- and difluorophenyl moieties

Abstract

New C-linked carbo-β-amino acids (β-Caas), Cbz-(S)-β-Caa-(NHBoc)-OMe (1) and Cbz-(R)-β-Caa-(NHBoc)-OMe (2), with an additional amine group (methylamino group of NHBoc) at the C-1 position of the lyxofuranoside side chain and Boc-(S)-β-Caa-(diFP)-OMe (3) and Boc-(R)-β-Caa-(diFP)-OMe (4), with a C-difluorophenyl (diFP) moiety at the anomeric position of the lyxofuranoside side chain were prepared from D-mannose. β-Peptides [tetra- and hexapeptides] were synthesized from these β-Caas, ‘epimeric’ [at the amine stereocentre (C_β)], using the concept of ‘alternating chirality’ to carry out their conformational studies [NMR (CDCl₃), CD and MD]. In the monomer design, it was envisaged that the presence of an additional amine group in 1 or 2 would help in solubilizing the peptides in water, while, the C-difluorophenyl (diFP) moiety of 3 and 4 is expected to enhance the biological activity. The peptides having 1 and 2, though could not retain their 12–10-mixed helices in water, have shown moderate activity against Gram positive and Gram negative bacterial strains. The peptides prepared from 3 and 4, much against our expectations, did not display any biological activity.