title: Enantioseparation and thermodynamic study of naphthalene derivatives, new melatoninergic agonists, on coated amylose [tris(S)-1-phenylethylcarbamate] stationary phase. Transposition to preparative scale.
abstract: This work reports a high-performance liquid chromatography normal-phase methodology to elucidate enantiomers of naphthalene derivatives, evaluated as melatoninergic agonists. For this purpose four different polysaccharide based chiral stationary phases were evaluated, namely Chiralcel OD-H (cellulose tris-3,5-dimethylphenylcarbamate), Chiralcel OJ (cellulose tris-methylbenzoate), Chiralpak AD (amylose tris-3,5-dimethylphenylcarbamate) and Chiralpak AS (amylose tris-(S)-1-phenylethylcarbamate) with different alcoholic modifiers on different amounts in n-heptane. A temperature study was carried out, between 20 and 40 °C and the apparent thermodynamic parameters were calculated thanks to the Van't Hoff linearization. For all compounds (except 3), ΔΔH° and ΔΔS° exhibited positive values ranging from 791.2 to 9999.3 J/mol and from 3.9 to 37.8 J/K/mol respectively, indicating entropically driven separations. Optimized conditions led to goof resolution of 2.37 for compound 1 on Chiralpak AS, with heptane-2-propanol 90:10 (v/v), at a temperature of 30 °C. Then they were transposed to the preparative scale for compound 1, generating 22 mg of each enantiomer with an 80% yield. The limits of detection and of quantification were determined to allow the calculation of the enantiomeric excess. They were found with very low values, equal to 0.32 and 1.05 µ m and 0.33 and 1.11 µ m, respectively, for peaks 1 and 2 of compound 1.
authors.affiliation: Université Lille Nord de France, UDSL, EA 4481 and EA GRIIOT, UFR Pharmacie, F-59000, Lille, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Landagaray
authors.forename: Saïd
authors.initials: S
authors.lastname: Yous
authors.forename: Claude
authors.initials: C
authors.lastname: Vaccher
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Lipka
mesh_terms: D000688:Amylose / Q000031:analogs & derivatives* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D008550:Melatonin / Q000819:agonists / Q000737:chemistry*; D015394:Molecular Structure; D009281:Naphthalenes / Q000819:agonists / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature; D013816:Thermodynamics
chemical_list: D009281:Naphthalenes; C106151:amylose tris(1-phenylethylcarbamate); D000688:Amylose; D008550:Melatonin
keywords: Van't Hoff linearization; chirality; naphthalene; polysaccharide stationary phase; preparative separation; thermodynamic parameters