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

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