Cyclic beta-tetra- and pentapeptides: synthesis through on-resin cyclization and conformational studies by X-ray, NMR and CD spectroscopy and theoretical calculations.
The solution-phase synthesis of the simplest cyclic beta-tetrapeptide, cyclo(beta-Ala)4 (4), as well as the solid-phase syntheses through side chain anchoring and on-resin cyclization of the cyclic beta3-tetrapeptide cyclo(-beta3hPhe-beta3hLeu-beta3hLys-beta3hGln-) (14) and the first cyclic beta3-pentapeptide cyclo(-beta3hVal-beta3hPhe-beta3hLeu-beta3hLys-beta3hLys-) (19) are reported. Extensive computational as well as spectroscopic studies, including X-ray and NMR spectroscopy, were undertaken to determine the preferred conformations of these unnatural oligomers in solution and in the solid state. cyclo(beta-Ala)4 (4) with no chiral side chains is shown to exist as a mixture of rapidly interchanging conformers in solution, whereas inclusion of chiral side chains in the cyclo-beta3-tetrapeptide causes stabilization of one dominating conformer. The cyclic beta3-pentapeptide on the other hand shows larger conformational freedom. The X-ray structure of achiral cyclo(beta-Ala)4 (4) displays a Ci-symmetrical 16-membered ring with adjacent C=O and N-H atoms pointing pair wise up and down with respect to the ring plane. CD spectroscopic examinations of all cyclic beta-peptides were undertaken and revealed results valuable as starting point for further structural investigations of these entities.
Büttner
Frank
F
Department of Chemistry, Organic Chemistry, Uppsala University, Sweden.
Norgren
Anna S
AS
Zhang
Suode
S
Prabpai
Samran
S
Kongsaeree
Palangpon
P
Arvidsson
Per I
PI
D000498:Allyl Compounds / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D002942:Circular Dichroism; D003500:Cyclization; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis*; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D014961:X-Ray Diffraction
D000498:Allyl Compounds; D000596:Amino Acids; D007202:Indicators and Reagents; D009842:Oligopeptides; D012997:Solvents