No abstract

The regioselectivity during transacetalization of benzophenone dimethyl acetal (4) with butane-1, 2, 4-triol (5) is controlled by the reaction conditions. Thermo-dynamic control leads predominantly to the 1, 3-dioxolane 6 whereas kinetic control favors the six-membered acetal 7. The amines 2a-e and 3a-e are synthesized from the alcohols 6 and 7 and are investigated in receptor binding studies with radioligands for their affinity to the phencyclidine binding site of the NMDA-receptor. In both series the primary amines 2a and 3a show the highest NMDA-receptor affinity (2a: Ki=3.38 microM; 3a: Ki=1.45 microM). The NMDA receptor slightly prefers the 1, 3-dioxane derivatives 3a and 3b compared to 2a and 2b (factor 2-3). Low interactions of the amines 3a and 3b with various receptor and reuptake systems indicate selectivity for the NMDA receptor. Surprisingly, the piperidine derivative 2e binds with high affinity at sigma1-receptors and, therefore, represents a novel lead compound for high affinity sigma1-receptor ligands.

Investigations to control the regioselectivity during the acetalization of pivalaldehyde (7) with butane-1,2,4-triol (4) were performed. Thermodynamic control led to the regioisomeric acetals 8 and 9 in the ratio 76:24, whereas kinetic control favored the fivemembered acetal 9 (8/9 30:70). Tosylation, nucleophilic substitution with NaN 3 , and subsequent methanolysis of the regioisomeric acetals 8 and 9 provided the regioisomeric 4-azidobutanediols 5 and 6, which are considered as valuable building blocks for the synthesis of novel NMDA-receptor antagonists.

Azides Azides P 0095Synthesis of Regioisomeric Azidobutanediols. -Acetalization of pivaldehyde (I) with the unsymmetrical triol (II) gives two regioisomeric acetals (III) and (IV). They are subsequently converted to regioisomeric azidobutanediols (VIII) and (XI), which are of interest in the chemistry of the NMDA-receptor antagonist dexoxadrol. -(AEPKERS, M.; WUENSCH*, B.; Synthesis 2004, 7, 1033-1036; Inst. Pharm. Med. Chem., Westfael. Wilhelms-Univ., D-48149 Muenster, Germany; Eng.) -Mais 37-061