Reaction SMILES: C(Cl)(Cl)Cl.[K+].[Br-].[CH3:7][C@H:8]1[C@@H:13]([O:14][C:15](/[CH:17]=[CH:18]/[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[CH2:12][C@@:11]2([O:34][C@@H:33]3[C@@H:28]([CH2:29][CH2:30][C@H:31]([C:35]([O:37][C@@H:38]4[O:43][C@H:42]([CH3:44])[C@@H:41]([OH:45])[C@H:40]([O:46][C:47]([CH3:49])=[O:48])[C@H:39]4[O:50][C@@H:51]4[O:56][C@H:55]([CH3:57])[C@@H:54]([OH:58])[C@H:53]([O:59][C:60]([CH3:62])=[O:61])[C@H:52]4[OH:63])=[O:36])[CH2:32]3)[C@@:25]32[O:27][CH2:26]3)[O:10][CH2:9]1.CC1C(OC(/C=C/C2C=CC=CC=2)=O)CC2(OC3C(CCC(C(OC)=O)C3)C32OC3)[O:67]C1>CO>[CH3:7][CH:8]1[CH:13]([O:14][C:15](/[CH:17]=[CH:18]/[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[CH2:12][C:11]2([O:34][CH:33]3[CH:28]([CH2:29][CH2:30][CH:31]([C:35]([O:37][CH:38]4[O:43][CH:42]([CH2:44][OH:67])[CH:41]([OH:45])[CH:40]([O:46][C:47]([CH3:49])=[O:48])[CH:39]4[O:50][CH:51]4[O:56][CH:55]([CH3:57])[CH:54]([OH:58])[CH:53]([O:59][C:60]([CH3:62])=[O:61])[CH:52]4[OH:63])=[O:36])[CH2:32]3)[C:25]32[O:27][CH2:26]3)[O:10][CH2:9]1
Reactant: CC(=O)O[C@@H]1[C@@H](O)[C@H](O[C@H]2[C@H](OC(=O)[C@H]3CC[C@@H]4[C@H](C3)O[C@@]3(C[C@H](OC(=O)/C=C/c5ccccc5)[C@H](C)CO3)[C@]43CO3)O[C@H](C)[C@@H](O)[C@@H]2OC(C)=O)O[C@H](C)[C@H]1O
Reactant: COC(=O)C1CCC2C(C1)OC1(CC(OC(=O)/C=C/c3ccccc3)C(C)CO1)C21CO1
Agent: [Br-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: CO
Product: CC(=O)OC1C(O)C(C)OC(OC2C(OC(=O)C3CCC4C(C3)OC3(CC(OC(=O)/C=C/c5ccccc5)C(C)CO3)C43CO3)OC(CO)C(O)C2OC(C)=O)C1O

Procedure:
The carbon tetrachloride (44 g) and methylene chloride (210 g) fractions were combined and chromatographed on Sephadex LH-20, eluting with methanol. A portion of the eluate from the Sephadex column was repeatedly chromatographed on a silica gel column. Elution between volumes 1530-2000 ml gave phyllanthostatin I (0.24 g) as an amorphous solid. Purity was determined by high pressure liquid chromatography (HPLC) on a μ Porasil column eluting with a mixture of methylene chloride, methanol and water (97:3:0.2). Phyllanthostatin 1 had the following characteristics: mp 125°-126° C.; FD mass spec. m/e 805 (M+ +H); [α]D26 -3.6° (c 0.83, CHCl3); λmaxMeOH (log ε) 216 (4.19), 222 (4.12) and 277 (4.29); nm; IR (KBr) νmax 3450, 1755, 1740, 1710, 1640, 1452, 1380, 1310, 1245, 1170, 1075 and 770 cm-1. Additional PS active fraction (Fraction D, 2.9 g) was chromatographed on silica gel-60 (Lobos C column); development of the column with chloroform (600 ml), 1%--(500 ml), 2%--(500 ml) and 3% methanol-chloroform (350 ml), followed by elution with 3% methanol-chloroform between volumes 350-620 ml gave material (2.49 g) which was further chromatographed on silica gel-60 (3 Lobos B columns) using methylene chloride-methanol-water (97/3.0/0.1) as eluant. Elution between volumes 990-1340 ml gave phyllanthoside (0.60 g) as an amorphous solid with the following characteristics: mp 125°-127° C.; FD mass spec. m/e 805 (M+ +H); [α]D22 +16.9° (C=0.71, CHCl3); λmaxMeOH nm (log ε) 216 (4.25), 222 (4.19) and 277 (4.34); IR (KBr) νmax 3475, 1750, 1735, 1710, 1640, 1452, 1380, 1311, 1253, 1173, 1080 and 770 cm- 1. Comparison of spectral data [Kupchan, S. M., supra] with that recorded for authentic phyllanthoside indicated that both are identical. Unfortunately, no specimens of phyllanthoside or phyllanthocin remain from Kupchan's original separations. Finally, chromatography on reverse phase (RP-2) silica (70→20%) aqueous methanol gradient) afforded 0.10 g of phyllanthostatin 2 as a colorless amorphous solid: mp 134°-136° C.; FD mass spectrum m/e 821 (M+ +H); [α]D24 +9.33° (c 0.75, CHCl3); λmaxMeOH nm (log ε) 216 (4.28), 222 (4.21) and 278 (4.38); IR νmax 3470, 1750, 1730, 1710, 1640, 1452, 1380, 1311, 1257, 1171, 1075 and 770 cm-1. The chromatography was conducted as follows: The biologically active fraction (Fraction E, 2.1 g) was chromatographed on silica gel-60 (Lobos C column); development of the column with chloroform (500 ml), 1%--(500 ml), 2%--(500 ml), 3%--(800 ml) and 4% methanol-chloroform (730 ml), followed by elution with 4% methanol-chloroform between volumes 730-3430 ml gave material (1.43 g) which was further chromatographed on RP-2 silica gel-60 (100 g) using 70%--(800 ml) to 20%--aqueous methanol (800 ml) gradient elution. Elution between volumes 750-830 ml gave phyllanthostatin 2 (0.10 g) as an amorphous solid. Additional silica gel chromatography yielded 0.26 g of phyllanthostatin 3 as a colorless amorphous solid: mp 126°-130°; FD mass spectrum m/e 323 (M+ +H); [α]D26 +15.7° (c 0.76, CHCl3); λmaxMeOH nm (log ε), 216 (4.25), 222 (4.18) and 278 (4.35); IR (KBr) νmax 3450, 1755, 1730, 1700, 1640, 1455, 1380, 1311, 1258, 1175, 1070 and 772 cm-1. The chromatography was conducted as follows: The biologically active fraction (Fraction F, 2.69 g) was chromatographed on silica gel-60 (Lobos C column); development with chloroform, 1%--, 2%--, 3%--(500 ml each) and 4% methanol-chloroform (650 ml), followed by elution with 4% methanol-chloroform between volumes 650-950 ml, gave material (0.88 g) which was further chromatographed on RP-2 silica gel-60 (180 g) using 60%--(900 ml) to 20% aqueous methanol (900 ml) gradient elution. Elution between volumes 350-800 ml gave material (0.45 g) which was chromatographed on silica gel-60 (3 Lobos A columns). Development with chloroform, 1%--, 2%--(150 ml each) and 3%-methanol-chloroform (100 ml) and elution with 3% methanol-chloroform between volumes 100-200 ml gave phyllanthostatin 3 (0.26 g) as an amorphous solid.