(αMe)Hyv: chemo-enzymatic synthesis, and preparation and preferred conformation of model depsipeptides

Abstract

By a chemo-enzymatic approach we performed a large-scale, stereoselective synthesis of the C^α-methylated α-hydroxy acid L-(αMe)Hyv. We also prepared model depsipeptides based on this sterically demanding residue in combination with the α-amino acids L-Ala, L-Val, and Aib. From solution (FT-IR absorption and ¹H NMR) and crystal-state (X-ray diffraction) conformational analyses we found that L-(αMe)Hyv forces depsipeptides to fold into right-handed β-turn/helical structures by analogy with the reported propensity of L-(αMe)Val, its α-amino acid counterpart.