Succinic anhydride → Succinylpodophyllotoxin

HRID 16662Notes

Reaction equation

[C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH2:3][CH2:2]1.[CH3:8][O:9][C:10]1[CH:11]=[C:12]([C@H:20]2[C@H:29]3[C:30]([O:32][CH2:33][C@@H:28]3[C@@H:27]([OH:34])[C:26]3[CH:25]=[C:24]4[O:35][CH2:36][O:37][C:23]4=[CH:22][C:21]2=3)=[O:31])[CH:13]=[C:14]([O:18][CH3:19])[C:15]=1[O:16][CH3:17]>N1C=CC=CC=1>[CH3:19][O:18][C:14]1[CH:13]=[C:12]([C@H:20]2[C@H:29]3[C:30]([O:32][CH2:33][C@@H:28]3[C@@H:27]([O:34][C:1]([CH2:2][CH2:3][C:4]([OH:6])=[O:5])=[O:7])[C:26]3[CH:25]=[C:24]4[O:35][CH2:36][O:37][C:23]4=[CH:22][C:21]2=3)=[O:31])[CH:11]=[C:10]([O:9][CH3:8])[C:15]=1[O:16][CH3:17]

Participants

Conditions

Temperature: 25 °C

Procedure

Succinic anhydride (0.9 g) was added to a solution of podophyllotoxin (207.2 mg, 0.5 mmol) in pyridine (12 mL). The resultant reaction mixture was stirred for 16 h at 25° C. Removal of solvent in vacuo afforded a residue. The crude residue was purified using a silica gel gravity column chromatography (35:7:1 CHCl3:MeOH:NH4OH) to give succinylpodophyllotoxin as white solid (198.5 mg, 80%) 1H NMR (500 MHz, DMSO-d6) δ 2.10 (d, J=5.4 Hz, 1H, H-4), 2.32 (dd, J=12.6, 4.8 Hz, 1H, H-2), 2.53 (m, 1H, H-3), 3.52 (s, 3H, OMe H-4′), 3.65 (dd, J=10.5, 7.5 Hz, 2H, H-11), 3.82 (s, 6H, two OMe groups, H-3′ and H-5′), 4.15 (t, J=7.9 Hz, 2H, CH2), 4.26 (t, J=7.9 Hz, 2H, CH2), 4.51 (d, J=5.4 Hz, 1H, H-1), 5.89 (s, 2H, OCH2), 6.00 (s, 2H, H-2′, H-6′), 6.67 (s, 1H, H-8), 6.94 (s, 1H, H-5), 12.15 (s, 1H, CO2H). Mass (ESI) (M−1) calcd for C26H26N2O11 513.15; found 512.93.

Workup

customThe resultant reaction mixture
customRemoval of solvent in vacuo
customafforded a residue
customThe crude residue was purified

Sources & evidence

ORD record: ord-7a86f4d8437c46f4bcc9a1d9bdf0f0d1
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07736624B2

Reaction notes

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