Synthesis Of (+)-(R)-5-Hydroxy-2-Methyl-2-Dipropylaminotetralin And (-)-(S)-5-Hydroxy-2-Methyl-2-Dipropylaminotetralin - Effects On Rat Hippocampal Output Of 5-Ht, 5-Hiaa, And Dopac As Determined By Invivo Microdialysis

Racemic 5-methoxy-2-methyl-2-dipropylaminotetralin (3) has been prepared by a short synthetic route, in which the N,N-dipropyliminium perchlorate of 5-methoxy-2-tetralone (4) is a key intermediate. Racemic 3 was resolved by crystallization of the corresponding diastereomeric di-p-toluoyltartrates. The enantiomeric excess (%ee) of the phenolic derivatives of (+)-(R)- and (-)-(S)-3 [(+)-(R)- and (-)-(S)-2] was determined by H-1 NMR spectroscopic analysis of the corresponding diastereomeric (-)-(R)-1,1'-binaphthyl-2,2'-diylphosphoric acid salts utilizing C-13 satellites. X-ray crystallography established the absolute configuration of (-)-(S)-2 . HCI. The enantiomers of 2 were tested for hippocampal output of 5-hydroxytryptamine, 5-hydroxyindoleacetic add, and dihydroxyphenylacetic acid in rats by use of in vivo microdialysis. The (-)-(S)-enantiomer appeared to affect 5-HT-turnover, whereas (+)-(R)-2 was inactive. Results obtained provide support for the previously reported hypothesis that the inactivity of (-)-(S)-2 at central DA receptors is caused by the steric bulk of the C(2)-methyl group. This makes it possible to define a ''DA D2 receptor essential volume.''