Synthesis and Structure of Novel G-Protein Coupled Receptor Ligands

Sammanfattning: A method based on h6-arenetricarbonylchromium chemistry has been developed for the synthesis of enantiopure 4-alkylated 3-(dipropylamino)chromans. The stereochemistry of these new serotonergic ligands was determined by a combination of X-ray crystallography, NMR spectroscopy and chemical correlation. A single-crystal X-ray diffraction study of the hydrochloride salt of the exo-[h 6-(3R)-(dipropylamino)chroman]tricarbonylchromium complex served to determine its relative and absolute configuration, and also as an aid in rationalising the stereochemical outcome of the benzylic alkylations.The stereochemistry of five derivatives of the novel pentacyclic compound (R)-1,11-methyleneaporphine was studied by X-ray diffraction, and their rigid conformation is compared with that of previously published aporphine derivatives.The conformational preferences of two achiral antimuscarinic derivatives of 3-(2-furanyl)quinuclidin-2-ene were studied by experimental (X-ray crystallography) and theoretical methods (ab initio and molecular mechanics). Introduction of a phenyl group in the 3-position of the furan ring causes a steric interaction that changes the conformation and conjugation of the molecule as compared to the 5-phenyl substituted derivative.The relative and absolute configurations of the chiral antimuscarinic stereoisomers of 3-(2,3-dihydrobenzofuran-2-yl)quinuclidine were determined by X-ray diffraction.