title: Synthesis and configuration determination of all enantiopure stereoisomers of the melatonin receptor ligand 4-phenyl-2-propionamidotetralin using an expedient optical resolution of 4-phenyl-2-tetralone.
abstract: An efficient and practical approach for the synthesis of all four stereoisomers of the MT(2) melatonin receptor ligand 4-phenyl-2-propionamidotetralin (4-P-PDOT), each in enantiomerically pure form (ee > 99.9%), was developed. The strategy involved an optical resolution procedure of the key precursor (±)-4-phenyl-2-tetralone with the unusual resolving agent (S)-mandelamide, through the formation of four dihydronaphtalene-spiro-oxazolidin-4-one diastereomers. Interestingly, NMR experimental observations in combination with geometric calculations, provided unambiguous configuration assignments of all stereocenters of the key spiro stereoisomers. Cleavage of each single spiro diastereomer under acidic conditions gave enantiopure (R)- or (S)-4-phenyl-2-tetralone, which were then converted to each 4-P-PDOT single enantiomer by using stereoselective reactions.
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, piazza Rinascimento 6, Urbino (PU), I-61029, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Lucarini
authors.forename: Silvia
authors.initials: S
authors.lastname: Bartolucci
authors.forename: Annalida
authors.initials: A
authors.lastname: Bedini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gatti
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Orlando
authors.forename: Giovanni
authors.initials: G
authors.lastname: Piersanti
authors.forename: Gilberto
authors.initials: G
authors.lastname: Spadoni
mesh_terms: D008024:Ligands; D008968:Molecular Conformation; D055620:Optical Phenomena; D044094:Receptors, Melatonin / Q000737:chemistry; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D044024:Tetralones / Q000737:chemistry*
chemical_list: C114459:4-phenyl-2-propionamidotetraline; C571207:4-phenyl-2-tetralone; D008024:Ligands; D044094:Receptors, Melatonin; D013764:Tetrahydronaphthalenes; D044024:Tetralones