*3.2. Materials*

The marine sponges *Agelas* spp. were collected off Kerama Islands, Okinawa, and identified by one of the authors (N.T.). The voucher specimens (SS-516 and SS-1302) were deposited in the Graduate School of Pharmaceutical Sciences, Tokushima University.

### *3.3. Extraction and Isolation*

The marine sponges *Agelas* spp. SS-516 (5.22 kg, wet weight) and SS-1302 (3.42 kg, wet weight) were separately extracted with MeOH to give the extracts (197.1 and 376.3 g, respectively), each of which was partitioned with *n*-hexane and 90% MeOH aq. The 90% MeOH aq.-soluble materials of SS-516 were separated by column chromatography on Diaion HP-20 (MeOH/H2O, 0:100–100:0) to give six fractions (frs. 1–6). Fr. 3 was subjected to silica gel column chromatography (CHCl3/MeOH/TFA, 95:5:0.1–80:20:0.1) to yield 12 fractions (frs. 3.1–3.12). Fr. 3.7 was applied to ODS MPLC (MeCN/H2O/TFA, 5:95:0.1–80:20:0.1), and then purified by ODS HPLC (YMC Hydrosphere C18, φ20 × 250 mm, MeCN/H2O/TFA, 35:65:0.1) to furnish agesasines A (**1**, 2.5 mg) and B (**2**, 2.2 mg). Separation of fr. 3.11 by ODS MPLC (MeCN/H2O/TFA, 5:95:0.1–80:20:0.1) gave five fractions (frs. 3.11.1–3.11.5). Tauroacidin A (124.1 mg) and taurodispacamide A (34.5 mg) were purified from fr. 3.11.3 by ODS MPLC (MeCN/H2O/TFA, 20:80:0.1).

The 90% MeOH aq.-soluble materials of SS-1302 were further partitioned between *n*-BuOH and water. The *n*-BuOH-soluble materials (58.0 g) were applied to silica gel column chromatography (CHCl3/MeOH/TFA, 9:1:0.1–5:5:0.1) to give six fractions (frs. 1- –6- ) including oroidin (17.1 g, fr. 3- ). Fr. 4- was subjected to MPLC on a Toyopearl HW-40F column (MeOH/H2O/TFA, 10:90:0.1–90:10:0.1), an MCI gel CHP 20P column (MeOH/H2O/TFA, 10:90:0.1–90:10:0.1) to yield seven fractions (frs. 4- .4.1–4- .4.7). Fr. 4- .4.3 was loaded to MPLC on an ODS column (MeCN/H2O/TFA, 10:90:0.1–60:40:0.1) to give six fractions (frs. 4- .4.3.1–4- .4.3.6), and then fr. 4- .4.3.3 was purified by ODS HPLC (COSMOSIL 5C18-MS-II, φ 20 × 250 mm, MeCN/H2O/TFA, 17:83:0.1). Further purification of fr. 4- .4.3.3.2 on ODS HPLC (YMC Hydrosphere C18, φ 10 × 250 mm, MeCN/H2O/TFA, 13:87:0.1) afforded 9-hydroxydihydrodispacamide (**3**, 5.0 mg), 9*E*-keramadine (**5**, 3.1 mg), and keramadine (6.7 mg). 9-Hydroxydihydrooroidin (**4**, 2.1 mg) was isolated from fr. 4- 4.3.3.3 by ODS HPLC (YMC Hydrosphere

C18, φ 10 × 250 mm, MeCN/H2O/TFA, 13:87:0.1). Fr. 4- .4.4 was subjected to ODS MPLC (MeCN/H2O/TFA, 10:90:0.1–50:50:0.1) and then ODS HPLC (YMC Hydrosphere C18, φ 10 × 250 mm, MeCN/H2O/TFA, 15:85:0.1) to furnish 2-bromo-9,10-dihydrokeramadine (2.1 mg). Fr. 5 was applied to MPLC on a Toyopearl HW-40F column (MeOH/H2O/TFA, 10:90:0.1–90:10:0.1) to give eight fractions (frs. 5- .1–5- .8). Fr. 5 was passed through an MCI gel CHP 20P column (MeOH/H2O/TFA, 10:90:0.1–100:0:0.1) and an ODS column (MeOH/H2O/TFA, 10:90:0.1–0:10:0.1) to afford nagelamide L (187.5 mg). Tauroacidin A and nagelamide L did not show optical rotations.

*Agesasine A* (**1**): Pale yellow amorphous solid; [α] 28 <sup>D</sup> 0 (*c* 0.10, MeOH); UV (MeOH) λmax 275 (ε 4900) nm; 1H and 13C NMR data (Table 1); ESIMS: *m*/*z* 391, 393, and 395 (1:2:1), [M + Na]+; HRESIMS: *m*/*z* 390.89045 [M + Na]<sup>+</sup> (calcd for C9H10N2O4Na79Br2, 390.89050).

*Agesasine B* (**2**): Pale yellow amorphous solid; [α] 28 <sup>D</sup> 0 (*c* 0.10, MeOH); UV (MeOH) λmax 274 (ε 3100) nm; 1H and 13C NMR data (Table 1); ESIMS: *m*/*z* 381, 383, and 385 (1:2:1), [M <sup>−</sup> H]−; HRESIMS: *m*/*z* 380.9088 [M − H]<sup>−</sup> (calcd for C10H11N2O4 79Br2, 380.9086).

*9-Hydroxydihydrodispacamide* (**3**): Pale yellow amorphous solid; [α] 27 <sup>D</sup> 0 (*c* 0.10, MeOH); UV (MeOH) λmax 223 (ε 3900) and 275 (3400) nm; 1H and 13C NMR data (Table 2); ESIMS: *m*/*z* 444, 446, and 448 (1:2:1), [M <sup>−</sup> H + Na]+; HRESIMS: *m*/*z* 443.92824 [M <sup>−</sup> H + Na]<sup>+</sup> (calcd for C11H13N5O3Na79Br2, 443.92828).

*9-Hydroxydihydrooroidin* (**4**): Pale yellow amorphous solid; [α] 27 <sup>D</sup> 0 (*c* 0.10, MeOH); UV (MeOH) λmax 276 (ε 3900) nm; 1H and 13C NMR data (Table 2); ESIMS: *m*/*z* 406, 408, and 410 (1:2:1), [M]+; HRESIMS: *m*/*z* 405.9510 [M]<sup>+</sup> (calcd for C11H14N5O2 79Br2, 405.9514).

*9E-Keramadine* (**5**): Pale yellow amorphous solid; UV (MeOH) λmax 271 (ε 3300) nm; 1H and 13C NMR data (Table 2); ESIMS: *m*/*z* 324 and 326 (1:1), [M]+; HRESIMS: *m*/*z* 324.04592 [M]<sup>+</sup> (calcd for C12H15N5O79Br, 324.04600).
