4-[(1R)-1-hydroxy-2-[4-(4-hydroxyphenyl)butylamino]ethyl]benzene-1,2-diol

Originator

Genesa,Genesa,UK

Uses

Arbutamine is a cardiac stimulant. Arbutamine stimulates adrenergic receptors.

Definition

ChEBI: Arbutamine is a catecholamine. It has a role as a beta-adrenergic agonist and a cardiotonic drug.

Manufacturing Process

(R)-Arbutamin was produced as follows: 89.3 mg of (-)-1-di(tbutyldimethylsiloxy) phenyl)-2-aminoethanol, 50.0 mg of 4-(4- methoxymethoxyphenyl)butanoic acid, diethylphosphorylcyanide, and triethylamine were dissolved in N,N-dimethylformamide at 0°C, reacted at room temperature, so as to obtain 108.6 mg (in a yield of 82%) of amide compound. The amide compound obtained was reduced lithium aluminium hydride in an ether solvent at reflux temperature, so as to quantitative obtain amine. And 55.6 mg of (R)-arbutamin which is intended compound was obtained by deprotecting the hydroxyl-protecting group of amine in a methanol-THF solvent at room temperature using hydrochloric acid. [α]D 25 = -17 (c 1.15, EtOH).
(-)-1-(Dibutyldimethylsiloxy)phenyl)-2-aminoethanol was obtained by a hydrogenization of (R)-1-(3,4-di(t-butyldimethylsiloxyphenyl)-2-nitroethanol on 10% Pd/C.
The last compound was prepared as follows: the hydroxyl groups of 3,4- dihydroxy-benzaldehyde was protected using t-butyldimethylsilylchloride (1). 100 mg (0.26 mmol) of 3,4-di(t-butyl-methylsiloxy)benzaldehyde was dissolved in 1 ml tetrahydrofurane under atmosphere of argon at -40°C, and 0.30 ml of metal complex from (S)-6,6'-bis(triethylsilylethynyl)-1,1-dihydroxy- 2,2'-binaphtalene (2) mixed with a solution of n-butyllitium in hexane.After stirring for 30 minutes, 79.4 mg (1.3 mmol) of nitromethane was added dropwise to the mixture. After 67 hour reaction time, 2 ml of 1 N aqueous solution of hydrochloric acid added to stop the reaction. Product was extracted with 50 ml ethyl acetate, dehydrated with anhydrous sodium sulfate and concentrated within evaporator followed by silica gel chromatography (nhexane/ acetone = 10/1), after which (R)-1-(3,4-di(t-butyldimethylsiloxy) phenyl)-2-nitroethanol with an optical purity of 92% e.e. was obtained in a yield of 93%.

brand name

Genesa (Gensia).

Therapeutic Function

Cardiotonic