The 2,2-disubstituted 2H-azirin-3-amines 5 (3-amino-2H-azirines) were used as synthons for alpha,alpha-disubstituted alpha-amino acids in the preparation of 16-membered cyclic depsipeptides 13. The linear precursors containing four alpha,alpha-disubstituted alpha-amino acids, the pentapeptides 12, were synthesized from beta-hydroxy acids 4 via the 'azirine/oxazolone method' (Scheme 2). The 16-membered cyclic depsipeptides 13 were prepared via 'direct amide cyclization' in good-to-excellent yields (Schemes 3 and 4). In addition to the desired cyclic monomer 13, which was obtained as the main product, the cyclodimer 14 could also be isolated. The cyclization conditions were investigated and found to be optimum with HCl in toluene at 100°. The structure and conformation of the cyclic depsipeptide 13b was established by X-ray crystallography.