5-aminooxazole as an internal traceless activator of C-terminal carboxylic acid: rapid access to diversely functionalized cyclodepsipeptides

A 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)]


Published in:
Chemistry--A European Journal, 12, 4, 1174-1184
Year:
2006
Keywords:
Peptides Role: SPN (Synthetic preparation) ; PREP (Preparation) (depsipeptides ; cyclo; prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazole ; trapping of iminium with carboxylic acid ; intramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation); Heterocyclic compounds Role: SPN (Synthetic preparation) ; PREP (Preparation) (macrocyclic ; nitrogen; prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazole ; trapping of iminium with carboxylic acid ; intramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation); Lactonization; Macrocyclization (macrolactonization; prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazole ; trapping of iminium with carboxylic acid ; intramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation); Addition reaction (nucleophilic; prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazole ; trapping of iminium with carboxylic acid ; intramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation); Cyclization; Fragmentation reaction; Protonation (prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazole ; trapping of iminium with carboxylic acid ; intramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation); Macrolides Role: SPN (Synthetic preparation) ; PREP (Preparation) (prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazole ; trapping of iminium with carboxylic acid ; intramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation) ; cyclodepsi peptide prepn domino process macrolactonization cyclization; aminooxazole protonation activation spirolactone nucleophilic addn fragmentation
Note:
CAN 144:350962
34-3
Amino Acids, Peptides, and Proteins
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
Journal
0947-6539
written in English.
62-53-3 (Aniline); 67-63-0 (2-Propanol); 75-08-1 (Ethanethiol); 75-65-0 (tert-Butanol); 100-01-6; 103-49-1; 111-42-2; 111-71-7 (Heptanal); 122-78-1 (Benzeneacetaldehyde); 156-87-6; 2508-29-4; 2937-99-7; 4048-33-3; 6688-11-5 (Cyclooctanecarboxaldehyde); 7783-06-4 (Hydrogen sulfide (H2S); 13325-10-5; 66877-05-2; 133437-08-8; 357277-74-8; 619335-48-7; 619335-54-5; 619335-56-7; 619335-58-9; 881303-94-2; 881303-97-5; 881304-20-7; 919475-13-1; 919475-26-6 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazole, trapping of iminium with carboxylic acid, intramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation); 18545-16-9P; 68750-25-4P; 357277-78-2P; 357277-79-3P; 357277-80-6P; 357277-81-7P; 357277-82-8P; 357277-83-9P; 357277-84-0P; 357277-85-1P; 357277-86-2P; 357277-87-3P; 881303-98-6P; 881304-08-1P; 881304-09-2P; 881304-10-5P; 881304-11-6P; 881304-12-7P; 881304-13-8P; 881304-14-9P; 881304-15-0P; 881304-16-1P; 881304-17-2P; 881304-18-3P; 881304-19-4P; 881304-21-8P; 881304-22-9P; 881304-23-0P; 881304-24-1P; 881304-25-2P; 881304-26-3P; 919475-40-4P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazole, trapping of iminium with carboxylic acid, intramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation); 357277-90-8P; 357277-91-9P; 357277-92-0P; 357277-93-1P; 357277-95-3P; 357277-96-4P; 357277-97-5P; 357277-98-6P; 357278-00-3P; 357278-01-4P; 357278-02-5P; 357278-03-6P; 357278-04-7P; 357278-05-8P; 357278-06-9P; 881303-87-3P; 881303-88-4P; 881303-89-5P; 881303-90-8P; 881303-91-9P; 881303-92-0P; 881303-93-1P; 881303-95-3P; 881303-96-4P; 881303-99-7P; 881304-00-3P; 881304-01-4P; 881304-02-5P; 881304-03-6P; 881304-04-7P; 881304-05-8P; 881304-06-9P; 881304-07-0P; 881304-27-4P; 881304-28-5P; 881304-29-6P; 881304-30-9P; 881304-31-0P; 881304-32-1P; 881304-33-2P; 881304-34-3P; 881304-35-4P; 881304-36-5P; 881304-37-6P; 881304-38-7P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of cyclodepsipeptides by macrolactonization via protonation of aminooxazole, trapping of iminium with carboxylic acid, intramol. nucleophilic addn. of tethered alc. to spirolactone and fragmentation)
Laboratories:




 Record created 2010-11-25, last modified 2018-01-28


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