Enantioselective chromatography and absolute configuration of N,N-dimethyl-3-(naphthalen-2-yl)-butan-1-amines: potential sigma1 ligands.
We describe the preparation of racemic N,N-dimethyl-3-(naphthalen-2-yl)-butan-1-amines, potential sigma1 ligands, and their resolution via chiral HPLC. In order to obtain enantiopure compounds, direct chromatographic methods of separation using chiral stationary phases were investigated. Different methods suitable for both analytical and semipreparative purposes are proposed. The best resolutions were achieved using cellulose tris (3,5-dimethylphenyl carbamate) (Chiralcel OD and OD-H) and amylose tris (3,5-dimethylphenyl carbamate) (Chiralpak AD). On the basis of the preliminary chromatographic results, the resolution of compound 1 was transferred onto a Chiralcel OD semipreparative column. The enantiomers were obtained in high enantiomeric excess. The configurational assignment was performed by circular dichroism. Computational analysis was used to explore the enantioselective recognition process of compound 1 with the Chiralcel OD stationary phase.
Collina
Simona
S
Dipartimento di Chimica Farmaceutica, Università di Pavia, Pavia, Italy.
Loddo
Guya
G
Urbano
Mariangela
M
Rossi
Daniela
D
Mamolo
Maria Grazia
MG
Zampieri
Daniele
D
Alcaro
Stefano
S
Gallelli
Andrea
A
Azzolina
Ornella
O
D000588:Amines / Q000032:analysis / Q000737:chemistry; D000688:Amylose / Q000031:analogs & derivatives / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002942:Circular Dichroism; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009281:Naphthalenes / Q000032:analysis / Q000737:chemistry; D048448:Phenylcarbamates / Q000737:chemistry; D013237:Stereoisomerism
D000588:Amines; D008024:Ligands; D009281:Naphthalenes; D048448:Phenylcarbamates; C065943:cellulose tris-3,5-dimethylphenyl-carbamate; C080033:Chiralpak AD; D002482:Cellulose; D000688:Amylose