Catechol Tetrahydroisoquinolines: Synthesis, Biological Activity, and Natural Occurrence in Portulaca oleracea as...

Catechol tetrahydroisoquinolines (THIQs) with structural novelty have been sporadically reported in Portulaca oleracea L., an edible vegetable and also a medicinal plant. However, their natural occurrence and biological activities are largely unknown. Using dopamine hydrochloride and aliphatic or aromatic aldehydes as substrates, 20 catechol THIQs with varied C1 side chains (A1-A20) were synthesized via an optimized mild phosphate-mediated Pictet-Spengler (P-S) reaction. Besides our previously developed AB-8 macroporous resin for the purification of hydrophilic THIQs, silica gel column chromatography employing ethyl acetate-methanol-ammonia or dichloromethane-methanol-85% formic acid as the eluent was optimized for the purification of lipophilic THIQs. Except for A1, A3, and A11, all compounds were synthesized for the first time using a mild phosphate-mediated P-S reaction, and A5, A10, A19, and A20 were novel compounds. Using UPLC-Q-TOF-ESI-MS/MS analysis and some synthesized compounds as reference, real-virtual-combined target screening of catechol THIQs was performed. A total of 29 catechol THIQs were simultaneously detected in P. oleracea for the first time, including 11 fatty alkane-connected ones (containing 3 new natural products and 5 new compounds), 9 fatty acid-connected ones (containing 7 new compounds), 1 amide-connected one, and 8 aryl ring-connected ones (containing 1 new compound and 1 new natural product). In vitro assay indicated that two catechol THIQs (6,7-dihydroxy-1-n-undecyl-1,2,3,4-tetrahydroisoquinoline and ethyl 5-(6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline)-n-valerate) exhibited antibacterial activity, and most of them displayed potent antioxidant, Fe²⁺-chelation, and α-glucosidase inhibition activities. This study demonstrated that catechol THIQs made up a group of bioactive alkaloids in P. oleracea.