title: Racemic and enantiopure synthesis and physicochemical characterization of the novel taste enhancer N-(1-carboxyethyl)-6-(hydroxymethyl)pyridinium-3-ol inner salt.
abstract: Convenient syntheses were developed to obtain on a multigram scale the novel taste enhancer N-(1-carboxyethyl)-6-(hydroxymethyl)pyridinium-3-ol 1, called alapyridaine, as a racemic mixture and as pure (+)-(S) and (-)-(R) enantiomers, respectively. 5-(Hydroxymethyl)-2-furaldehyde was used as key intermediate and was reacted with l-alanine under alkaline conditions to obtain racemic 1. Alternatively, reductive amination of 5-(hydroxymethyl)-2-furaldehyde with Raney-Ni/hydrogen and l- or d-alanine followed by mild oxidation led to (+)-(S)-1 and (-)-(R)-1, respectively. Racemization was promoted under alkaline and boiling conditions via a carbanion, the formation of which was facilitated by the electron-withdrawing effect of the iminium cation and the resonance-stabilizing capacity of the pyridinium moiety. Under these conditions, 1 was obtained in a 1:1 mixture of the phenol (1) and phenolate (1-H) forms as shown by X-ray diffraction. Racemic 1 formed monoclinic crystals of high molecular organization in which the phenol-type (RS)-1, the phenolate-type (RS)-1-H, sodium cations, and ethanol molecules are present. The crystal structure of [Na(1)(1-H).(C(2)H(6)O)] shows one-dimensional mu(2)-bridging-oxygen polymers stabilized by a three-dimensional network of ionic, hydrogen bond, and pi-stacking interactions with channels occupied by solvent molecules.
authors.affiliation: Nestlé Research Center, Vers-chez-les-Blanc, 1000 Lausanne 26, Switzerland.
authors.forename: Renaud
authors.initials: R
authors.lastname: Villard
authors.forename: Fabien
authors.initials: F
authors.lastname: Robert
authors.forename: Imre
authors.initials: I
authors.lastname: Blank
authors.forename: Gérald
authors.initials: G
authors.lastname: Bernardinelli
authors.forename: Tomislav
authors.initials: T
authors.lastname: Soldo
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmann
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D012964:Sodium / Q000737:chemistry
chemical_list: D011725:Pyridines; C472251:alapyridaine; D012964:Sodium; D000409:Alanine; D010100:Oxygen