Synthesis, Purification, and Selective β2-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, 1, 2, and 12, present in the medicinal plant Portulaca oleracea, as well as their analogues 3-11, 13, and 14, 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 α1B-, β1-, or β2-adrenergic receptors indicated that 12 and 2, compounds that are present in P. oleracea, possessed the most potent β2-adrenergic receptor agonist activity and 2 was a selective β2-adrenergic receptor agonist at the concentration of 100 μM. Both 12 and 2 exhibited dose-dependent bronchodilator effects on the histamine-induced contraction of isolated guinea-pig tracheal smooth muscle, with EC50 values of 0.8 and 2.8 μM, respectively. These findings explain the scientific rationale of P. oleracea use as an antiasthmatic herb in folk medicine and provide the basis for the discovery of novel antiasthma drugs.