Synthesis, Purification, and Selective β 2 -AR Agonist and Bronchodilatory Effects of Catecholic Tetrahydroisoquinolines from Portulaca oleracea

A green, biomimetic, phosphate-mediated Pictet-Spengler reaction was used in the synthesis of three catecholic tetrahydroisoquinolines, , , and , present in the medicinal plant , as well as their analogues - , , and , with dopamine hydrochloride and aldehydes as the substrates. AB-8 macroporous resin column chromatography was applied for purification of the products from the one-step high-efficacy synthesis. It eliminated the difficulties in the isolation of catecholic tetrahydroisoquinolines from the aqueous reaction system and unreacted dopamine hydrochloride. Activity screening in CHO-K1/Gα15 cell models consistently expressing α -, β -, or β -adrenergic receptors indicated that and , compounds that are present in , possessed the most potent β -adrenergic receptor agonist activity and was a selective β -adrenergic receptor agonist at the concentration of 100 μM. Both and exhibited dose-dependent bronchodilator effects on the histamine-induced contraction of isolated guinea-pig tracheal smooth muscle, with EC values of 0.8 and 2.8 μM, respectively. These findings explain the scientific rationale of use as an antiasthmatic herb in folk medicine and provide the basis for the discovery of novel antiasthma drugs.