Synthesis of novel σ-receptor ligands from methyl α-d-mannopyranoside

For the first time a monosaccharide (methyl α-d-mannopyranoside) has been used as starting material for the synthesis of novel σ-receptor ligands. The hept-3-ulopyranoside dimethyl ketals 14 and 15 were obtained from the nitrile 7 via two synthetic routes. After selective hydrolysis of the ketone dimethyl acetal, various amino substituents were introduced into position 3. High σ1-receptor affinity and selectivity was attained with equatorially arranged amino substituents in position 3 and a dichlorophenylacetamide moiety in position 7. The anomeric mixture of dimethylamines 26α/β displayed the highest σ1-receptor affinity (Ki = 21 nM) within this small series of test compounds.

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