The synthesis of several 18-membered cyclodepsipeptides with an alternating sequence of a,a-disubstituted a-amino acids and a-hydroxy acids (compounds 14a–14e) is described. The ring closure via macrolactonization
was accomplished by treatment of a diluted suspension of the corresponding linear precursors 12a–12e in toluene with HCl gas, i.e., the so-called 'direct amide cyclization'. The incorporation of the a,a-disubstituted a-amino acids was achieved via the 'azirine/oxazolone method' with 2H-azirin-3-amines of type 6 and 9 as building blocks. The structure of the cyclic depsipeptide 14a was established by X-ray crystallography.