*3.3. Extraction and Isolation*

Air-dried leaves and twigs of *C. hypoleucophylla* (17.0 kg) were extracted three times with 95% ethanol at room temperature for 72 h each time. The extract was evaporated under reduced pressure to get a crude extract (3.6 kg). Next, the ethanol extract of *C. hypoleucophylla* was suspended and dissolved in H2O and then partitioned with ethyl acetate to obtain an ethyl acetate layer (118.3 g). The the ethyl acetate layer was further partitioned between hexanes and 75% MeOH to acquire hexanes and MeOH layers, respectively.

Due to the results of the cytotoxic assay, the MeOH layer (45.6 g) was selected for further isolation. At first, it was loaded on a normal-phase silica gel open column and was eluted by stepwise hexanes with ethyl acetate (1:0~0:1) followed by stepwise ethyl acetate with methanol (1:0~0:1) to obtain seven subfractions (CH1~7), according to TLC analysis. The third sub-fraction, CH3, was isolated on Sephadex LH-20 and eluted with MeOH to afford four subfractions (CH3-1–4). Then, repeated column chromatography isolation on CH3-3 yielded CH3-3-1–5 fractions. CH3-3-2 (500.3 mg) was separated by silica gel CC (dichloromethane/MeOH, 100:1→0:1) to afford more subfractions (CH3-3-2-1–6). Fr. CH3-3-2-6 was purified by normal-phase HPLC using a Phenomenex Luna-CN column (hexane/dichloromethane/methanol, 30:10:1, 1.5 mL/min) to give compounds **2** (33.1mg), **3** (7.2 mg), **4** (62.7 mg), and 5 (26.7 mg). Fr. CH3-3-2-4 was isolated by reverse-phase HPLC using a CN column and gave compounds **1** (1.9 mg) and 7 (0.7 mg). Fr. CH3-3-3 was subjected to silica gel CC (CH2Cl2/MeOH, 1:0→0:1) followed by NP-CN HPLC and elution with (hexane/dichloromethane/methanol, 40:10:1, 2.0 mL/min) to obtain compound **8** (9.8 mg). In addition, Fr. CH3-2 was separated by normal-phase silica gel CC with hexane/dichloromethane/methanol (100:40:1→0:0:1) to afford Frs. CH3-2-1–5. Fr. CH3-2-5 was purified by silica gel CC (CH2Cl2/MeOH, 1:0→0:1) followed by RP-phenyl-hexyl HPLC (methanol/H2O, 65/35, 2.0 mL/min) to give compounds **6** (2.5 mg) and **9** (7.0 mg).
