biostudies-literatureSalib MNDivision of ChemistryNational Center for Research ResourcesNCRR NIH HHSNIAID NIH HHSNational Institutes of Health3269-3278https://www.ebi.ac.uk/biostudies/studies/S-EPMC11894641biostudies-literatureUnknown90(9)The configurational analysis of amino acids (AAs) in natural product peptides, often containing nonproteinogenic AAs, is mostly carried out by the venerable Marfey's method using a chiral derivatizing agent (CDA) 1-fluoro-2,4-dinitrophenyl-5-l-alaninamide (l-FDAA)─Marfey's reagent─which undergoes <i>S</i><sub>N</sub>Ar reaction of the 1° amino group. The resulting AA-DAA derivatives are mostly well-separated by reversed-phase HPLC, but some DAA derivatives resist resolution. Here, we report the synthesis and characterization of two CDAs: l-FDTA (<b>4</b>) in which the l-alanine-derived auxiliary is replaced by l-tryptophanamide and (<i>S</i>)-FDNE (<b>3</b>) where the auxiliary is <i>S</i>-(6-methoxynaphth-2-yl)-1-ethylamine. Side-by-side comparisons of the two reagents were carried out byThe Journal of organic chemistrySynthesis and Performance of l-Tryptophanamide and (<i>S</i>)-1-(Naphthalen-2'-yl)ethanamine-Based Marfey-Type Derivatives for Amino Acid Configurational Analysis: Diastereomeric Resolutions Directed by π-Cation Bonding.PMC11894641S10RR025636R01 AI1007786CHE0741968S10 RR025636R01 AI100776Salib MNMolinski TFfalseSynthesis and Performance of l-Tryptophanamide and (<i>S</i>)-1-(Naphthalen-2'-yl)ethanamine-Based Marfey-Type Derivatives for Amino Acid Configurational Analysis: Diastereomeric Resolutions Directed by π-Cation Bonding.The configurational analysis of amino acids (AAs) in natural product peptides, often containing nonproteinogenic AAs, is mostly carried out by the venerable Marfey's method using a chiral derivatizing agent (CDA) 1-fluoro-2,4-dinitrophenyl-5-l-alaninamide (l-FDAA)─Marfey's reagent─which undergoes <i>S</i><sub>N</sub>Ar reaction of the 1° amino group. The resulting AA-DAA derivatives are mostly well-separated by reversed-phase HPLC, but some DAA derivatives resist resolution. Here, we report the synthesis and characterization of two CDAs: l-FDTA (<b>4</b>) in which the l-alanine-derived auxiliary is replaced by l-tryptophanamide and (<i>S</i>)-FDNE (<b>3</b>) where the auxiliary is <i>S</i>-(6-methoxynaphth-2-yl)-1-ethylamine. Side-by-side comparisons of the two reagents were carried out by2025-01-01T00:00:00Z2025 Mar2025-04-06T22:39:44.593Z2025-04-04T02:54:22.742ZS-EPMC118946413997784210.1021/acs.joc.4c02882