Molecules 2019, 24, 1059
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Synthesis of 7-hydroxy-1,6,6-trimethyl-6,7-dihydrophenanthro[1,2-b]furan-10,11-dione (10) [33]
To a solution of 11 (30 mg, 0.098 mmol) in MeOH (2 mL) was added NaBH4 (11 mg, 0.300 mmol).
The reaction mixture was stirred at rt for 1 h and then evaporated the solvent, diluted with H2O, and
extracted with EtOAc (50 mL
anhydrous Na2SO4, and concentrated in vacuo. The residue was further purified by silica gel column,
×
3). The combined organic layer was washed with brine, dried over
and elution with 1%–2% MeOH in CH2Cl2 afforded the desired product 10 (27 mg, 90%) as a red solid.
m.p. 185.2-188.5 ◦C. 1H-NMR (400 MHz, CDCl3)
δ
7.87 (d, J = 10.2 Hz, 1H), 7.64–7.55 (m, 2H), 7.24
(s, 1H), 6.39 (dd, J = 10.2, 4.4 Hz, 1H), 4.08 (d, J = 4.5 Hz, 1H), 2.26 (s, 3H), 1.39 (s, 3H), 1.28 (s, 3H).
13C-NMR (126 MHz, CDCl3)
184.2, 175.6, 161.2, 147.1, 141.5, 135.8, 135.5, 131.5, 127.7, 125.0, 123.6,
δ
122.1, 121.2, 120.2, 72.5, 40.0, 26.3, 21.9, 8.8.
Synthesis of 1,6,6-trimethyl-7,8-dihydrophenanthro[1,2-b]furan-9,10,11(6H)-trione (13) and
1,6,6-trimethylphenanthro[1,2-b]furan-9,10,11(6H)-trione (14)
To a solution of
2-Iodoxybenzoic acid (1.082 g, 3.864 mmol). The reaction mixture was stirred at 60 ◦C microwave for
3 h and then diluted with H2O and extracted with EtOAc (150 mL 3). The combined organic layer
8 (200 mg, 0.644 mmol) in toluene (4 mL) and DMSO (2 mL) was added
×
was washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was
further purified by silica gel column, and elution with 30%–40% EtOAc in hexane afforded 13 (55 mg,
27%, Rf = 0.4 in 40% EtOAc/hexane) and 14 (38 mg, 19%, Rf = 0.2 in 40% EtOAc/hexane) as an orange
1
solid. Compound 13: H-NMR (300 MHz, CDCl3)
δ
7.72 (d, J = 8.2 Hz, 1H), 7.57 (d, J = 8.2 Hz, 1H),
7.26 (d, J = 1.4 Hz, 1H), 2.92 (t, J = 7.2◦Hz, 2H), 2.26 (d, J = 1.3 Hz, 3H), 2.07 (t, J = 7.2 Hz, 2H), 1.34 (s,
6H). Compound 14: m.p. 158.3–160.8 C.1H-NMR (400 MHz, CDCl3)
δ 7.81 (d, J = 8.3 Hz, 1H), 7.72 (d,
J = 8.3 Hz, 1H), 7.27 (s, 1H), 6.80 (d, J = 10.2 Hz, 1H), 6.48 (d, J = 10.2 Hz, 1H), 2.26 (s, 3H), 1.50 (s, 6H).
13C-NMR (126 MHz, CDCl3)
δ 185.8, 183.4, 179.3, 159.6, 154.6, 151.8, 141.9, 135.3, 132.8, 131.6, 128.9,
127.4, 124.5, 121.3, 120.9, 38.3, 29.4, 8.7. MS (ESI, [M + H]+) m/z 307.4. HRMS (ESI) calcd for C19H15O4,
307.0965; found, 307.0967.
Synthesis of 1,6,6-trimethylphenanthro[1,2-b]furan-9,10,11(6H)-trione (14)
To a solution of 13 (44 mg, 0.14 mmol) in toluene (3 mL) was added 2,3-Dichloro-5,6-dicyano-
1,4-benzoquinone (DDQ, 49 mg, 0.21 mmol). The reaction mixture was stirred at 80 ◦C for 36 h and
then diluted with H2O and extracted with EtOAc (100 mL
washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was further
×
3). The combined organic layer was
purified by silica gel column, and elution with 40% EtOAc in hexane afforded 14 (31 mg, 70%).
Synthesis of 1-(hydroxymethyl)-6,6-dimethylphenanthro[1,2-b]furan-9,10,11(6H)-trione (15)
To a solution of 14 (30 mg, 0.098 mmol) in 1,4-dioxane (2 mL) was added selenium dioxide (44 mg,
◦
0.392 mmol). The reaction mixture was stirred at 100 C for 36 h and then diluted with H2O and
extracted with EtOAc (50 mL
anhydrous Na2SO4, and concentrated in vacuo. The residue was further purified by silica gel column,
×
3). The combined organic layer was washed with brine, dried over
and elution with 1%–2% MeOH in CH2Cl2 afforded the desired product 15 (5 mg, 16%) as an orange
solid. m.p. 195.5–198.4 ◦C. 1H-NMR (400 MHz, CDCl3)
δ
7.85 (d, J = 8.3 Hz, 1H), 7.75 (d, J = 8.3 Hz,
1H), 7.45 (s, 1H), 6.82 (d, J = 10.3 Hz, 1H), 6.47 (d, J = 10.2 Hz, 1H), 4.69 (s, 2H), 1.51 (s, 6H). 13C-NMR
(126 MHz, CDCl3)
δ 184.7, 183.3, 179.4, 161.1, 154.6, 152.5, 141.2, 135.7, 132.8, 131.8, 128.5, 127.4, 126.1,
124.7, 120.5, 55.2, 38.4, 29.5. HRMS (ESI, [M + H]+) calcd for C19H15O5, 323.0914; found, 323.0901.
3.2. Biology
hIDO-1 enzymatic assay. The hIDO-1 enzymatic assay was performed as described previously [36].
Briefly, a standard reaction mixture (30
µL) containing 100 mM potassium phosphate buffer (pH
6.5), 40 mmol/L ascorbic acid and 0.01% Triton X-100, 200
µ
g/mL catalase, 20 mol/L methylene
µ