83247-89-6

Upstream product

• 121617-59-2 (R)-(-)-11-methoxyaporphine 
• 83207-97-0 (R)-(-)-11-methoxyaporphine hydrochloride 
• 213390-15-9 (R)-11-tert-Butoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline 
• 58-00-4 apomorphin 
• 213390-14-8 Trifluoro-methanesulfonic acid (R)-11-tert-butoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-10-yl ester 
• 84156-35-4 (R)-10,11-(isopropylidenyldioxy)aporphine 
• 213390-13-7 (R)-11-tert-Butoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-10-ol 

Relevant academic research and scientific papers

Preparation of (R)-11-hydroxyaporphine directly from (R)-10,11- dihydroxyaporphine ((R)-apomorphine)

A Regioselective synthesis of (R)-11-hydroxyaporphine 2 directly from (R)-10,11-dihydroxyaporphine ((R)-apomorphine, 1) is described for the first time. The isopropylidene ketal ring of 10,11-(isopropyl-idenyldioxy)aporphine 5 obtained by the isopropylidenation of apomorphine was regioselectively opened by ten equivalents of trimethylaluminum to give (R)-10-hydroxy-11- tert-butyloxyaporphine 6. The free 10-hydroxyl position of 6 was triflated with N-phenyltrifluoromethanesulfonimide and potassium carbonate under reflux to give (R)-10-[(trifluoromethyl)sulfonyloxy]-11-tert-butyloxyaporphine 7. The reduced product, 11-tert-butyloxyaporphine 8 was prepared from 7 by a palladium-catalyzed hydrogenolysis. The ether cleavage of (R)-11-tert- butyloxyaporphine with 48% hydrobromic acid afforded the desired (R)-11- hydroxyaporphine 2 in good yield.

Aporphines as Antagonists of Dopamine D-1 Receptors

The aporphine alkaloids are a class of compounds known to possess activity at both D-1 and-D-2 dopamine receptors. (R)-Apomorphine and (S)-bulbocapnine are examples of compounds which have agonist and antagonist activity, respectively, at D-1 receptors.A series of optically pure aporphines was synthesized and their activiy at D-1 and D-2 dopamine receptors was studied.The (R)-aporphines uniformly had greater affinity for both D-1 and D-2 receptors than their S antipodes.Dihydroxy compound (R)-apomorphine, in accord with previous studies, was found to be a D-1 agonist.Aporhines possesing a single hydroxy group at C-11 are antagonists at the D-1 receptor.The corresponding methoxy compounds are virtually inactive at dopamine receptors.The most potent compounds, (R)-11-hydroxyaporhine (R-14) and (R)-10-bromo-11-hydroxyaporphine (R-26), are more potent than bulbocapnine as D-1 antagonists but are not as selective.A model for binding of aporphines to the D-1 receptor was formulated in which binding interactions between the receptor and the basic nitrogen and the C-11 hydroxy group of the aporphine are required for high-affinity binding to the receptor.The absolute configuration at C-6a determines the orientation of the N-6 lone pair and binding is optimal for the 6aR series.The agonist or antagonist activity of an aporphine is determined by the presence or absence, respectively, of a hydroxy group at C-10.A hydrophobic binding site may be present and may account for the high antagonist activity of (S)-bulbocapnine.