153944-89-9Relevant academic research and scientific papers
Homochiral 2,4-Disubstituted 1,3-Dioxanes from (S)-(-)-Malic Acid: Stereoselective Synthesis and Investigation of the NMDA Receptor Affinity of All Four Stereoisomers
Wuensch, Bernhard,Diekmann, Heike,Hoefner, Georg
, p. 1273 - 1278 (2007/10/02)
Starting from a single enantiomerically pure compound, (S)-(-)-malic acid, all four stereoisomeric 4-dimethylaminomethyl-2-phenyl-1,3-dioxanes (S,S)-15, (R,R)-15 (S,R)-16, and (R,S)-16 are prepared: Transacetalisation of benzaldehyde dimethyl acetal (6b) with (S)-(-)-methyl 2,4-dihydroxybutyrate (7a), which is obtained by chemoselective BH3 reduction of (S)-(-)-malic acid monoester 8b, yields the diastereomeric 1,3-dioxane derivatives (S,S)-10 and (R,S)-11 in a 85:15 ratio.LDA deprotonation of (S,S)-10 followed by protonation leads to C-4 epimerisation .The thermodynamically controlled 88:12 equilibrium of (R,R)-10 and (S,R)-11 is reached by treatment of (S,R)-11 with acid.Aminolysis with dimethylamine and subsequent LiAlH4 reduction transform the four stereoisomeric esters (S,S)-10, (R,R)-10, (S,R)-11 and (R,S)-11 to give the amines (S,S)-15, (R,R)-15, (S,R)-16 and (R,S)-16, respectively.In the 3H-(+)-MK 801 displacement experiment (S,S)-15, (R,R)-15, (S,R)-16 and (R,S)-16 show a very little affinity to the phencyclidine binding site in the cation channel associated with the NMDA receptor. - Key Words: Butyric acid derivatives, (S)-(-)-24-dihydroxy-/ 1,3-Dioxanes/ NMDA antagonists, noncompetitive
