title: Synthesis of N-Fmoc-(2S,3S,4R)-3,4-dimethylglutamine: An application of lanthanide-catalyzed transamidation.
abstract: N-Fmoc-(2S,3S,4R)-3,4-dimethylglutamine (6) was synthesized from tert-butyl N-Boc-(2S,3S,4R)-dimethylpyroglutamate (13). This synthesis involved selective deprotection of a Boc group from a lactam nitrogen in the presence of a tert-butyl ester, Fmoc protection of the lactam, and a lanthanide-catalyzed transamidation reaction of the Fmoc-protected lactam, using ammonia and dimethylaluminum chloride. The scope of Lewis acid-catalyzed transamidation of acylated lactams was explored through the variation of lanthanide, lactam, acyl group, amine, and aluminum reagent. The reactivity of various metal triflates was found to vary in the following qualitative order: Yb approximately Sc > Er approximately Eu approximately Sm > Ce approximately Ag(I) > Cu(II) approximately Zn. Intriguingly, catalysis was only observed when ammonia was the nitrogen nucleophile; addition of other amidoaluminum complexes to acyl lactams was found to be insensitive to the addition of lanthanides.
authors.affiliation: Department of Chemistry and Cancer Center, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-2084, USA.
authors.forename: Selçuk
authors.initials: S
authors.lastname: Calimsiz
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lipton
mesh_terms: D000586:Amination; D002384:Catalysis; D047630:Depsipeptides / Q000737:chemistry; D005973:Glutamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D007769:Lactams / Q000138:chemical synthesis*; D028581:Lanthanoid Series Elements / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: C419323:3,4-dimethylglutamine; D047630:Depsipeptides; D007769:Lactams; D028581:Lanthanoid Series Elements; C504700:N-Fmoc-(2S,3S,4R)-3,4-dimethylglutamine; C418139:callipeltin A; C474170:papuamide A; C474171:papuamide B; D005973:Glutamine