*3.3. Extraction and Isolation*

The freeze-dried and powdered biomass (dry weight 600 g) of the above environmental collection was exhaustively extracted in 2:1 CH2Cl2/MeOH (8×). The extracts were dried under vacuum and then rinsed with H2O (3×) to remove residual sea salt, affording 3.1 g

of an organic crude extract. This material was subjected to vacuum liquid chromatography (VLC) separation over normal-phase silica gel column chromatography (200–300 mesh) using a stepwise gradient (10% EtOAc/hexanes, 20% EtOAc/hexanes, 40% EtOAc/hexanes, 60% EtOAc/hexanes, 80% EtOAc/hexanes, 100% EtOAc, 10% MeOH/EtOAc, and 20% MeOH/EtOAc). The column was eluted to provide 8 fractions: A (200.9 mg), B (300.5 mg), C (316.4 mg), D (250.6 mg), E (150.9 mg), F (707.5 mg), G (506.7 mg), and H (259.6 mg). Fraction C was further separated by RP-18 MPLC with a 120 g Biotage SNAP Cartridge, KP-C18-HS, and a gradient solvent system (60% to 100% MeOH/H2O in 60 min) to generate subfractions C1–C6 with yields of 40 mg, 40 mg, 60 mg, 30 mg, 20 mg, and 70 mg, respectively. Subfraction C3 was additionally fractionated using a Waters ACQUITY UPLC equipment instrument equipped with a PDA detector on a reversed-phase Phenomenex Kinetex C18 column (5 μm, 5 × 250 mm, Phenomenex) using MeCN/H2O as a mobile phase, at a flow rate of 1 mL/min. The gradient program was 50–100% MeCN/H2O in 20 min with a linear gradient elution. The eluent was delivered to an automatic fraction collector for timed sampling every 0.75 min from 6.2 min to 15.2 min, and all the fractions were dried in glass tubes and weighed. In total, 12 fractions, Fr.C3–1−C3–12 were obtained from the subfraction C3 with the yields 1 mg, 6 mg, 1 mg, 2 mg, 3 mg, 2 mg, 3 mg, 1 mg, 1 mg, 1 mg, 2 mg, and 2 mg, respectively. Fraction C3–5, corresponding to a 3 mg sample collected around a UV 210 nm peak at *t*<sup>R</sup> = 9.6, was found to contain the pure compound **1** after it was analyzed by LC-MS and 1D NMR.

#### *3.4. Isolated Materials (New Natural Products)*

*Wenchangamide A (1)*: white powder; [α] 17 *<sup>D</sup>* −315 (*c* 0.1, MeOH); UV (MeOH) *λ*max (log *ε*) = 218 (3.92), 275 (3.04) nm; IR (KBr) νmax 3350 (br), 2921, 2815, 2742, 1612, 1515, 1505, 1487, 1416, 1235 cm−1;for 1H NMR and 13C NMR data see Table 1; HR-ESI-MS [M + Na]<sup>+</sup> *m/z* 1233.7748 (calcd. for C64H106N8O14Na+, 1233.7721).
