Homochirale 2,4-disubstituierte 1,3-Dioxane aus (S)-(−)-Äpfelsäure: Stereoselektive Synthese und Untersuchung der NMDA-Rezeptoraffinität aller vier Stereoisomerer
✍ Scribed by Wünsch, Bernhard ;Diekmann, Heike ;Höfner, Georg
- Publisher
- John Wiley and Sons
- Year
- 1993
- Tongue
- English
- Weight
- 646 KB
- Volume
- 1993
- Category
- Article
- ISSN
- 0947-3440
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✦ Synopsis
Homochiral 2,4‐Disubstiuted 1,3‐Dioxanes from (S)‐(−)‐Malic Acid: Stereoselective Synthesis and Investigation of the NMDA Receptor Affinity of All Four Stereoisomers
Starting from a single enantiomerically pure compound, (S)‐(−)‐malic acid, all four stereoisomeric 4‐dimethylaminomethyl‐2‐phenyl‐1,3‐dioxanes (S,S)‐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 BH~3~ 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 [(S,S)‐10:(S,R)‐11 = 30:70]. 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 LiAlH~4~ 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 ^3^H‐(+)‐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.