Conformational Studies on Peptides of α‐Aminoxy Acids with Functionalized Side‐Chains

Abstract

Peptides of homochiral alpha-aminoxy acids of nonpolar side chains can form a 1.8(8)-helix. In this paper, we report the conformational studies of alpha-aminoxy peptides 1-3, which have functionalized side chains, in both nonpolar and polar solvents. (1)H NMR, XRD, and FTIR absorption studies confirm the presence of the eight-membered-ring intramolecular hydrogen bonds (the N-O turns) in nonpolar solvents as well as in methanol. CD studies of peptides 1-3 in different solvents indicate that a substantial degree of helical content is retained in methanol and acidic aqueous buffers. The introduction of functionalized side chains in alpha-aminoxy peptides provides opportunities for designing biologically active peptides.

Synthesis of L‐Lys‐Aminoxy‐Goralatide

“…In this work, we used N ‐Z‐D‐lysine 14 as starting material; the d ‐isomer was transformed into the l ‐isomer of lysine on the fifth step of synthesis . We first modified the α ‐amino group into the α ‐hydroxy group of 15, which was then acylated with acetic anhydride in the presence of DMAP in pyridine to give 16 (Scheme ).…”

“…After 45 min at r.t., the reaction was quenched by the addition of 2 M HCl until the aqueous layer was below pH 2. The aqueous layer was extracted with Et 2 O (three times), and the combined organic extracts were dried over MgSO 4 , filtered, and concentrated at reduced pressure to yellow oil, which was used for the next step without further purification [28]. Crude compound 16 and tert-butyl alcohol (0.74 g, 10 mmol) was dissolved in DCM (15 ml).…”