The hyphenated technique, high-performance liquid chromatography-solid-phase extraction-nuclear magnetic resonance spectroscopy (HPLC-SPE-NMR), has been applied for rapid identification of novel natural products in crude extracts of Hubertia ambavilla and Hubertia tomentosa. The technique allowed full or partial identification of all major extract constituents and demonstrated the presence of unusual quinic acid derivatives containing the (1-hydroxy-4-oxocyclohexa-2,5-dienyl)acetyl residue that exhibit strongly coupled ABXY patterns, the parameters of which were obtained by spin simulations. Using homo- and heteronuclear 2D NMR data acquired in the HPLC-SPE-NMR mode, complete structure determination of three new natural products, i.e., 3,5-di-O-caffeoyl-4-O-[(1-hydroxy-4-oxocyclohexa-2,5-dienyl)acetyl]quinic acid (1), its 2-hydroxy derivative (2), and 3,5-di-O-caffeoyl-4-O-[(4-hydroxyphenyl)acetyl]quinic acid (3), was performed. Finally, targeted isolation of 1 was achieved by SPE fractionation and preparative HPLC, followed by evaluation of its antioxidant and antimicrobial activity. In contrast to chlorogenic acid and 3,5-di-O-caffeoylquinic acid, which act as antioxidants, compound 1 proved at the same conditions to possess prooxidant activity in an assay evaluating the oxidation of human low-density lipoprotein induced by Cu(2+).