Convenient primary amidation of N-protected phenylglycine and dipeptides without racemization or epimerization

Protecting‐Group‐Free Amidation of Amino Acids using Lewis Acid Catalysts

“…Cbz-PhGly + NH 4 Cl yields amide in 43 %y ield, 46 % ee using ethyl chloroformate, 58 C, 1h). [25] Overall,t he methods howed similar trends in reactivity to the stoichiomet- Table 2). The relevance of this chemistry can easily be exemplified by the fact that most of the amides synthesized in Scheme 4( or their enantiomers) are members of aw ell-documented class of potent anticonvulsants and agentsf or neuropathic pain treatment, commonly referred to as primary aminoacid derivatives(PAADs).…”

“…Sarcosine, l ‐α‐aminobutyric acid and phenylglycine all underwent successful amidation (Scheme I), although the latter ( 1 ee ) underwent complete racemization, as expected based on its known propensity to racemise even under mild conditions (e.g. Cbz‐PhGly+NH 4 Cl yields amide in 43 % yield, 46 % ee using ethyl chloroformate, 5° C, 1 h) . Overall, the method showed similar trends in reactivity to the stoichiometric approach (vide supra, Table ).…”

Influence of stereochemistry on the activity of rapadocin, an isoform-specific inhibitor of the nucleoside transporter ENT1

“…Boc-Phg-OH was activated as mixed acid anhydride and coupled with N-methyl phenylalanine 5 to give the highly diastereoselective dipeptide 4 with excellent d.r. ratio (>20:1) 20,22 , as determined by 1 H-NMR (Table 1).…”