Orthogonally Protected N-Methyl-Substituted α-Aminoglycines

Abstract

Title glycine derivatives FmocNRlCH(NR2Boc)CO2H (I; Fmoc =9-fluorenyl-methyloxycarbonyl; Boc = Me3CO2C; Rl = H, Me; R2 = H, Me), useful as templates for the introduction of desired functionalities into peptides, were prepared by condensation of glyoxylic acid and carbamates Fmoc-NH-Rl (Rl = H, Me), followed by conversion with Me2CHSH of the resulting FmocNRlCH(OH)CO2H to FmocNR1CH(SCHMe2)CO2H (Rl = H, Me) which were further treated with Boc-NH-R2 (R2 = H, Me) in the presence of N-bromosuccinimide. A simple and efficient synthesis of Fmoc-NH-Me and Boc-NH Me is also reported.

Betidamino Acid Scan of the GnRH Antagonist Acyline

“…N α -Boc-4-nitro- l - and - d -phenylalanine, N α -Boc-4-amino- l - and - d -phenylalanine, and N α -Boc-[4- N -(9-fluorenylmethoxycarbonyl)amino]- l - and - d -phenylalanine were synthesized according to previously published procedures , The methyl benzhydrylamine resin used for peptide synthesis was obtained according to published procedures. , Resins with substitutions varying from 0.4 to 0.7 mequiv/g were used. All solvents were reagent grade or better.…”

“…We have described synthetic pathways to orthogonally protected betidamino acid and methylbetidamino acid scaffolds ( N ‘-monoacylated aminoglycine derivatives) ,, for solid-phase peptide synthesis and their use in the design of selected bioactive GnRH analogues. In short, FmocNR 1 CH(NR 2 Boc)CO 2 H (R 1 = H, Me; R 2 = H, Me), useful as templates for the introduction of desired functionalities into peptides, were prepared by condensation of glyoxylic acid and carbamates Fmoc-NH−R 1 (R 1 = H, Me), followed by conversion with Me 2 CHSH of the resulting FmocNR 1 CH(OH)CO 2 H to FmocNR 1 CH(SCHMe 2 )CO 2 H (R 1 = H, Me) which were further treated with Boc-NHR 2 (R 2 = H, Me) in the presence of N -bromosuccinimide 17 to give the desired products.…”

Corticotropin Releasing Factor (CRF) Agonists with Reduced Amide Bonds and Ser7Substitutions

“…Peptides 23 − 33 that incorporated derivatized α-aminoglycine moieties were synthesized according to the procedure of Jiang et al , After lactam cyclization, racemic Boc-Agl(Fmoc), Boc,Me-Agl(Fmoc), or Boc-Agl(Me, Fmoc) was coupled to the peptide−resin with BOP in 50% NMP/DCM. The appropriate nitrogen was deblocked and derivatized by either acetylation or formylation as desired.…”

“…Synthesis of Agl-Containing Peptides. Racemic Boc-Agl(Fmoc), Boc,Me-Agl(Fmoc), and Boc-Agl(Me, Fmoc) were kindly provided by G. Jiang as previously published . Since the Agl derivatives were the last amino acids to be coupled to the resin, the lactam formation between residues 30 and 33 was completed prior to the final Agl(R) (R = H, Me) coupling and derivatization.…”

“…Racemic Boc-Agl-(Fmoc), Boc,Me-Agl(Fmoc), and Boc-Agl(Me, Fmoc) were kindly provided by G. Jiang as previously published. 36 Since the Agl derivatives were the last amino acids to be coupled to the resin, the lactam formation between residues 30 and 33 was completed prior to the final Agl(R) (R ) H, Me) coupling and derivatization. The protected Agl(R) was coupled to 0.25-0.5 mmol of peptide-resin using standard protocol with BOP in 50% NMP/DCM, adjusted to pH 9 with 3 equiv of diisopropylethylamine for 2-3 h. In some cases recouplings were necessary until a satisfactory ninhydrin test resulted.…”