From mannose to morphan analogues: methyl α-D-mannoside as chiral building block for the synthesis of mono- and bicyclic σ receptor ligands.
| Autor: | Wiedemeyer K; Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Münster, Germany., Wünsch B |
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| Jazyk: | angličtina |
| Zdroj: | Carbohydrate research [Carbohydr Res] 2012 Oct 01; Vol. 359, pp. 24-9. Date of Electronic Publication: 2012 May 12. |
| DOI: | 10.1016/j.carres.2012.05.006 |
| Abstrakt: | Previously the synthesis and high σ(1) receptor affinity of mannose derived pyrans 3-5 with equatorially oriented amino groups have been reported. Herein the synthesis and receptor affinities of the corresponding axially substituted pyrans and oxa-morphans are described. Key step in the diastereoselective synthesis was an S(N)2 substitution of tosylate 10 with NaN(3). Heating of the azide 6 with acid led unexpectedly to the oxa-morphan 13, which showed remarkable affinity toward the σ(1) receptor (K(i)=860 nM). The benzylamine 15α and the dimethylamine 16α were obtained by reduction of the azide 6 and subsequent reductive alkylation. In contrast to the equatorial amines 3-5, the axial amines 15α and 16α did not interact with the σ(1) receptor or another investigated receptor system. (Copyright © 2012 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
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