Molecular Networking-Guided Discovery of Phenolic Constituents from Fruits of <i>Mallotus philippinensis</i>

The fruits of <i>Mallotus philippinensis</i> are an underexplored source of chemically diverse and biologically active natural products, previously reported to exhibit anti-inflammatory, antiviral, and cytotoxic activities. In this study, ion identity molecular networking (IIMN) resulted in the discovery of four previously undescribed phenolic derivatives (runakamalas A-D (<b>1</b>-<b>4</b>)), together with the known compounds mallotophilippen F (<b>5</b>), 3',4'-dihydroxyrottlerin (<b>6</b>), and 4'-hydroxyrottlerin (<b>7</b>). Their structures were elucidated by HRESIQTOF-MS, MS/MS fragmentation analysis, and NMR spectroscopy. The absolute configurations of <b>1</b> and <b>2</b> were clarified by vibrational circular dichroism (VCD) spectroscopy supported by quantum-chemical calculations, while the enantiomers of racemic <b>3</b> were separated by chiral-phase HPLC, and their absolute configurations were determined by a comparison of experimental and TDDFT-calculated ECD spectra. Among the new isolates, <b>4</b> is distinguished by a linear C-8-C-1'-C-4' chain, an unusual structural feature compared with other phloroglucinol derivatives reported from this species. In addition, the structure of compound <b>5</b> was confirmed. All isolated compounds were evaluated for their cytotoxicity against the human neuroblastoma SH-SY5Y cell line and for their antioxidant activity using the DPPH radical scavenging assay.