title: From mannose to morphan analogues: methyl α-D-mannoside as chiral building block for the synthesis of mono- and bicyclic σ receptor ligands.
abstract: 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.
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Münster, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Wiedemeyer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wünsch
mesh_terms: D000588:Amines / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D008024:Ligands; D008358:Mannose / Q000737:chemistry*; D008766:Methylmannosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D000588:Amines; D008024:Ligands; D008766:Methylmannosides; D017480:Receptors, sigma; C008466:methylmannoside; D008358:Mannose