Synthese cyclischer Depsipeptide durch direkte Amid-Cyclisierung: 12gliedrige Depsipeptide mit alternierender Sequenz von α-Hydroxy- und α-Aminosaeuren

Article abstract of DOI:10.1002/hlca.19900730126

Synthesis of Cyclic Depsipeptides via Direct Amide Cyclization: Cyclic Depsipeptides with 12-Ring Atoms and Alternating Sequence of α-Hydroxy and α-Amino Acids - - The reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine (1; R1=R2=R3=R4=Me) with α-hydroxycarboxylic acids, followed by selective hydrolysis of the terminal dimethylamide group yields the dipeptide analogues 15a and 18b (Schemes 3 and 4).After protection of the OH group (-> 16a and 19, resp.), coupling with the C-terminus-protected derivatives 14 and 18a, respectively, by a modified 1,1'-carbonyldiimidazole procedure followed by hydrolysis gives the linear depsipeptides 17c and 20, respectively.Treatment with HCl gas in toluene at 100 deg C leads to the cyclic depsipeptides 21 and 22 in very good yield.The two model reactions show that the 'azirine/oxazolone-method', combined with the 'direct amide cyclization' is a versatile procedure for the synthesis of cyclic depsipeptides containing α,α-disubstituted α-amino acids.