AbstractThe synthesis and conformational analysis of several polydepsipeptides containing alkyl or polar residues are reported. Five separate routes to the synthesis of depsipeptide monomers and two methods of polymerization are decribed. Polydepsipeptides containing alanine, valine, leucine, lactic acid, α‐hydroxyisovaleric acid, glutamic acid, and lysine were prepared and their conformations in solution analyzed. Helix‐to‐coil transitions for specific polydespsipeptides are obsurved in single organic solvents such as chloroform, tetrahydrofuran, or trifluoroethanol. A statistical thermodynamic theory of polymer melting successfully describes the observed transitions and allows quantitative determination of the tendency of specific amino acid residues to form helical