Bughin, CarineZhao, GangBienayme, HuguesZhu, Jieping2010-11-252010-11-252010-11-25200610.1002/chem.200500703https://infoscience.epfl.ch/handle/20.500.14299/58456A conceptually novel macrolactonization protocol has been developed. It is a domino process involving a sequence of: (1) protonation of 5-aminooxazole leading to the electrophilic iminium salt; (2) trapping of the iminium species by the neighboring C-terminal carboxylic acid leading to a putative spirolactone; and (3) intramol. nucleophilic addn. of the tethered alc. to the spirolactone followed by fragmentation. The strategically incorporated 5-aminooxazole serves as an internal traceless activator of the neighboring C-terminal carboxylic acid, since it became an integral part of the peptide backbone after cyclization. No coupling reagent is required and the entire sequence is triggered by just a few equiv. of trifluoroacetic acid under very mild conditions (MeCN as the solvent at room temp.). The spirolactone as an activated form of the carboxylic acid has been evidenced by a sulfur-migration expt. By combining with a three-component synthesis of 5-aminooxazole, a two-step synthesis of structurally complex cyclodepsipeptides from readily accessible starting materials was developed. [on SciFinder (R)]Peptides Role: SPN (Synthetic preparation)PREP (Preparation) (depsipeptidescyclo; prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazoletrapping of iminium with carboxylic acidintramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation); Heterocyclic compounds Role: SPN (Synthetic preparation)PREP (Preparation) (macrocyclicnitrogen; prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazoletrapping of iminium with carboxylic acidintramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation); Lactonization; Macrocyclization (macrolactonization; prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazoletrapping of iminium with carboxylic acidintramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation); Addition reaction (nucleophilic; prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazoletrapping of iminium with carboxylic acidintramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation); Cyclization; Fragmentation reaction; Protonation (prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazoletrapping of iminium with carboxylic acidintramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation); Macrolides Role: SPN (Synthetic preparation)PREP (Preparation) (prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazoletrapping of iminium with carboxylic acidintramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation)cyclodepsi peptide prepn domino process macrolactonization cyclization; aminooxazole protonation activation spirolactone nucleophilic addn fragmentationtext::journal::journal article::research article