The Facile Production of N-Methyl Amino Acids via Oxazolidinones

Abstract

A range of oxazolidinones derived from N-carbamoyl α-amino acids were prepared by an efficient method as key intermediates in the synthesis of N-methyl amino acids and peptides. The method was readily applied to most α-amino acids except those with basic side chains. The oxazolidinones were converted by reductive cleavage into N-methyl α-amino acids.

Halogenated Fatty Acid Amides and Cyclic Depsipeptides from an Eastern Caribbean Collection of the Cyanobacterium Lyngbya majuscula

“…The desired mono-methylated product was separated from starting material and di-methylated product by reversed phase HPLC (Atlantis dC18, Waters, 3.0 × 250 mm) using 0.10% aqueous formic acid as the mobile phase. The resulting N -methyl-L-threonine (98% purity by ELSD) demonstrated 1 H NMR and 13 C NMR signals consistent with literature values 29. MS analysis confirmed the identification: ESI-TOF-MS m / z 134.0805 [M+H] + (calcd for C 5 H 12 NO 3 , 134.0812); ESI-MS/MS ( m/z 134.1 fragmented using 50% collision energy) m/z 98, 88, and 70.…”

Intramolecular Suzuki–Miyaura Reaction for the Total Synthesis of Signal Peptidase Inhibitors, Arylomycins A2 and B2

“…[24,29] Reasoning that the formation of the phenoxide could render the a-CH of Hpg less prone to deprotonation, thus reducing the likelihood of racemization, we decided to leave the phenol group of Hpg unprotected during the synthesis. l-Hydroxyphenylglycine (8) was first quantitatively N-tert-butoxycarbonyl (Boc) protected (Boc 2 O, aqueous NaOH, dioxane, RT) to give 9, which was subsequently converted into oxazolidinone 10 (paraformaldehyde, toluene sulfonic acid (p-TsOH), reflux).…”

Studies of 2-Substituted 1,3-Oxazolidin-5-ones and 1,3-Oxazinan-6-ones as Precursors for the Synthesis ofN-Alkyl-β-Amino Acids

“…We first concentrated efforts on the synthesis of 2-substituted-1,3-oxazinan-6-ones to provide access to N-alkyl-b-amino acids. The Cbz-N-b-amino acid 5 was subjected to condensation conditions used previously, [6] only varying paraformaldehyde to benzaldehyde (Scheme 3). However, under these conditions, no 2-substituted-1,3-oxazinan-6-one 6 was formed.…”

“…[4][5][6][7][8] Ben-Ishai [12] originally demonstrated formaldehyde can be condensed with an amino acid Scheme 3. Synthesis of 2-substituted-1,3-oxazinan-6-ones.…”

“…[3] In previous studies, we have shown that 1,3-oxazolidin-5-ones 1 are useful substrates for the synthesis of N-methyl-a-amino acids 2 and Nmethyl-b-amino acids 3 (Scheme 1). [4][5][6][7][8][9] In addition, we have also shown that the homologous 1,3-oxazinan-6-ones 4 are versatile precursors for gaining access to a range of N-methyl-b-amino acids 3 (Scheme 2). [7][8][9] Further, we provided one example of an N-alkyl-a-residue.…”