1115323-56-2Relevant academic research and scientific papers
Synthesis and NMDA receptor affinity of ring and side chain homologues of dexoxadrol
Sax, Michael,Froehlich, Roland,Schepmann, Dirk,Wuensch, Bernhard
supporting information; experimental part, p. 6015 - 6028 (2009/05/31)
Novel dexoxadrol derivatives with an expanded oxygen heterocycle (1,3-dioxane instead of 1,3-dioxolane), an enlarged distance between the two heterocycles, and an additional oxo group in the 4-position of the piperidine ring were synthesized and pharmacologically evaluated. The synthesis comprises a hetero-Diels-Alder reaction of imines with Danishefsky's diene (3), followed by a Lewis acid catalyzed conjugate reduction of the resulting dihydropyridones and hydrogenolytic debenzylation. The required aldehydes were synthesized by transacetalization of benzophenone dimethyl acetal (8) with pentane-1,3,5-triol (7), butane-1,2,4-triol (15), and 4-benzyloxybutane-1,3-diol (31), respectively, and subsequent Swern oxidation. Homodexoxadrols 39 were synthesized by the Cagliotti method with the use of p-toluenesulfonylhydrazide and NaBH4 for the removal of the oxo group. The diastereomers were separated and the relative configuration was assigned by X-ray crystal structure analysis and comparison of spectroscopic and chromatographic data. Receptor binding studies with the radioligand [3H]-(+)-MK-801 demonstrated that an expanded O-heterocycle, an enlarged distance between the heterocycles, and an additional oxo group led to a considerable loss of affinity towards the phencyclidine binding site of the NMDA receptor. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
