Solid-phase synthesis of β-oligopeptides

Abstract

Fmoc-N-Protected β-amino acids of (S)-configuration bearing the side chains of Ala, Val, Leu, and Phe in the 3-and 2-position have been prepared (1c-4c and 1d-4d). Manual solid-phase synthesis (ortho-chlorotrityl-chloride resin) of the β-hepta-peptides H-β3-HVal-β3-HAla-β 3-HLeu-β3-HPhe-β3-HVal-β 3HAla-β3-HLeu-OH (9) and H-β2-HVal-β2-HAla-β 2-HLeu-β2-HPhe-β2-HVal-β 2-HAla-β2-HLeu-OH (10), and, for comparison, of the corresponding α-heptapeptide H-Val-Ala-Leu-Phe-Val-Ala-Leu-OH (8) was achieved under standard conditions (HPLC/NMR identification). With the β3-peptide 9, the yield and purity of the crude product are similar to those of the α-peptide 8, while the β2-peptide synthesis needs to be optimized. CD measurements show that the β-peptides have helical secondary structures in MeOH, while the α-peptide does not.