3-(Dimethylamino)-2,2-dimethyl-2H-azirine as an α-Aminoisobutyric-Acid (Aib) Equivalent: Cyclic Depsipeptides via Direct Amide Cyclization

Article abstract of DOI:10.1002/hlca.19870700209

In MeCN at room temperature, 3-(dimethylamino)-2,2-dimethyl-2H-azirine (1) and α-hydroxycarboxylic acids react to give diamides of type 8.Selective cleavage of the terminal N,N-dimethylcarboxamide group in MeCN/H2O leads to the corresponding carboxylic acids 13.In toluene/PhSH, phenyl thioesters of type 11 are formed.Starting with diamides 8, the formation of morpholin-2,5-diones 10 has been achieved either by direct amide cyclization via intermediate 1,3-oxazol-5(4H)-ones 9 or via base-catalyzed cyclization of the phenyl thioesters 11.Reaction of carboxylic acids with 1, followed by selective amide hydrolysis, has been used for the construction of peptides from α-hydroxy carboxylic acids and repetitive α-aminoisobutyric-acid (Aib) units.Cyclization of 14a, 17a, and 20a with HCl in toluene at 100 deg C gave the 9-, 12-, and 15-membered cyclic depsipeptides 15, 18, and 21, respectively.