Synthesis of enantiopure pyrrolidine-derived peptidomimetics and oligo-beta-peptides via nucleophilic ring-opening of beta-lactams.
The synthesis of the two enantiomers of pyrrolidine-derived spiro beta-lactams by resolution with D- and L-Boc phenylalanine is described. The potential of these optically active spiro beta-lactams on the synthesis of peptidomimetics as analogues of melanostatin is evaluated. Theoretical studies of several models, at the Becke3LYP/6-31+G* level of theory, together with previous experimental evidences from our group, gathered by NMR, allow us to design structures that can efficiently mimic some biologically active peptide-type molecules. On the other hand, the spiro beta-lactams have shown their utility in the preparation of beta-peptides. As an example, a homo-tetra-beta-peptide was synthesized. This research will continue in the future in order to obtain higher peptides with potential biological activity.
Macías
Alberto
A
Departamento de Química Organica e Inorganica, Universidad de Oviedo, Julian Clavería 8, 33006 Oviedo, Spain.
Ramallal
Antonio Morán
AM
Alonso
Eduardo
E
del Pozo
Carlos
C
González
Javier
J
D015195:Drug Design; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis*; D011759:Pyrrolidines / Q000737:chemistry*; D013237:Stereoisomerism; D047090:beta-Lactams / Q000737:chemistry*
D009842:Oligopeptides; D011759:Pyrrolidines; D047090:beta-Lactams; D009075:MSH Release-Inhibiting Hormone; C032519:pyrrolidine