Journal of Natural Products
Article
21.5 h under N2. The reaction mixture was cooled to room
temperature, filtered with EtOAc, and concentrated in vacuo. The
residue was purified by silica gel column chromatography (n-hexane/
EtOAc = 9:1) to produce O-prenyl compound 7 (185.1 mg, 60%) as a
silica gel column chromatography (n-hexane/EtOAc = 3:2) to give
cubic yellow crystals (1.27 g, 83%). mp = 154−156 °C. H NMR
1
(400 MHz, CDCl3): δ 7.91 (d, J = 12.4 Hz, 1H), 6.44 (d, J = 12.4 Hz,
1H), 6.22 (s, 1H), 5.18 (s, 2H), 3.80 (q, J = 6.1 Hz, 1H), 3.47 (s,3H),
3.16 (s, 3H), 2.92 (s, 3H), 2.88 (dd, J = 17.2 and 5.6 Hz, 1H), 2.64
(dd, J = 17.0 and 5.4 Hz, 1H), 1.75 (d, J = 8.0 Hz, 1H), 1.43 (s, 3H),
1.38 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 190.09, 165.68, 159.12,
154.15, 154.01, 105.92, 98.69, 97.42, 95.22, 94.02, 77.66, 68.70, 56.33,
45.09, 37.25, 26.30, 24.85, 22.12. HRMS (ESI): m/z calculated for
C18H26O6 [M + H]+, 352.1760; found, 352.1754.
1
colorless oil. H NMR (400 MHz, CDCl3): δ 6.43 (d, J = 1.2 Hz,
1H), 6.30 (d, J = 1.2 Hz, 1H), 5.39 (t, J = 6.6 Hz, 1H), 5.15 (s, 2H),
5.14 (s, 2H), 4.49 (d, J = 6.8 Hz, 2H), 3.47 (s, 3H), 3.45 (s, 3H), 2.47
(s, 3H), 1.75 (s, 3H), 1.70 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
201.75, 159.51, 157.22, 155.21, 137.91, 119.33, 116.32, 95.99, 95.05,
94.79, 94.46, 65.63, 56.32, 56.16, 32.53, 25.74, 18.24. HRMS (ESI):
m/z calculated for C17H25O6 [M + H]+, 325.1651; found, 325.1647.
1-(6-Hydroxy-2,4-bis(methoxymethoxy)-3-(3-methylbut-2-en-1-
yl)phenyl)ethanone (8). A solution of compound 7 (180.1 mg, 0.55
mmol) in N,N-diethylaniline (2 mL) was placed in a vessel suited for
microwave irradiation and irradiated at 210 °C for 1.0 h. The mixture
was washed with aqueous 10% HCl (5 mL), H2O, and brine, dried
over Na2SO4, and concentrated in vacuo. The residue was purified by
silica gel column chromatography (n-hexane/EtOAc = 19:1) to
produce the target compound 8 (160.0 mg, 89%) as a colorless oil. 1H
NMR (400 MHz, CDCl3): δ 12.95 (s, 1H), 6.47 (s, 1H), 5.22 (s,
2H), 5.15 (t, J = 5.8 Hz, 1H), 4.96 (s, 2H), 3.52 (s, 3H), 3.46 (s, 3H),
3.31 (d, J = 6.0 Hz, 2H), 2.70 (s, 3H), 1.77 (s, 3H), 1.69 (s, 3H). 13C
NMR (100 MHz, CDCl3): δ 203.88, 163.47, 161.57, 157.12, 131.62,
122.97, 116.17, 110.97, 101.38, 98.81, 93.85, 58.35, 56.31, 31.42,
25.69, 23.08, 17.87. HRMS (ESI): m/z calculated for C17H25O6 [M +
H]+, 325.1651; found, 325.1646.
3-Hydroxy-9-iodo-5-(methoxymethoxy)-2,2-dimethyl-3,4-
dihydropyrano[2,3-f ]chromen-10(2H)-one (12). A mixture of
compound 11 (170.0 mg, 0.48 mmol) in MeOH (5 mL) was stirred
at room temperature for 10.5 h and then concentrated in vacuo to give
a reddish black residue. To remove residual I2, the residue was treated
with saturated aqueous Na2S2O3 until the mixture became clear. The
mixture was then extracted with DCM, and the resulting off-white
solid was purified by silica gel chromatography (n-hexane/EtOAc =
1
3:2) to give a white solid (107.1 mg, 91%). mp = 134−136 °C. H
NMR (400 MHz, CDCl3): δ 8.07 (s, 1H), 6.65 (s, 1H), 5.26 (s, 2H),
3.86 (q, J = 8.0 Hz, 1H), 3.50 (s, 3H), 2.92 (dd, J = 17.5 and 5.2 Hz,
1H), 2.71 (dd, J = 17.5 and 5.6 Hz, 1H), 2.22 (d, J = 7.0 Hz, 1H),
1.44 (s, 3H), 1.41 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 171.25,
159.35, 157.90, 155.39, 153.67, 106.55, 94.40, 93.60, 89.69, 78.36,
68.35, 56.60, 44.29, 26.36, 24.73, 21.47. HRMS (ESI): m/z calculated
for C16H18IO6 [M + H]+, 433.0148; found, 433.0141.
3-Hydroxy-5-(methoxymethoxy)-9-(4-methoxyphenyl)-2,2-di-
methyl-3,4-dihydropyrano[2,3-f ]chromen-10(2H)-one (13). A mix-
ture of aryl 12 (1.0 g, 2.31 mmol), 4-methyphenylboronic acid (527.8
mg, 3.47 mmol), Pd(OAc)2 (10.4 mg, 2 mol %), K2CO3 (480.1 mg,
3.47 mmol), and PEG-400 (8.0 g) was stirred at 45 °C for the
indicated time until complete consumption of the starting material, as
monitored by gas chromatography (GC). The mixture was added to
brine (15 mL) and extracted 4 times with Et2O (4 × 15 mL). The
solvent was concentrated in vacuo, and the crude product was purified
by silica gel column chromatography (n-hexane/EtOAc = 1:1) to
produce compound 13 (808.1 mg, 85%) as a white solid. mp = 156−
158 °C. 1H NMR (400 MHz, CDCl3): δ 7.73 (s, 1H), 7.46 (d, J = 8.4
Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 6.67 (s, 1H), 5.27 (s, 2H), 3.86 (q,
J = 6.0 Hz, 1H), 3.82 (s, 3H), 3.51 (s, 3H), 2.93 (dd, J = 17.4 and 5.2
Hz, 1H), 2.72 (dd, J = 17.5 and 5.5 Hz, 1H), 2.13 (d, J = 7.4 Hz, 1H),
1.44 (s, 3H), 1.40 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 175.37,
159.34, 158.93, 158.05, 154.15, 150.08, 130.51, 125.91, 124.44,
113.67, 105.93, 94.31, 93.78, 78.08, 68.43, 56.49, 55.30, 26.43, 24.67,
21.47. HRMS (ESI): m/z calculated for C23H25O7 [M + H]+, 413.16;
found, 413.1592.
3,5-Dihydroxy-9-(4-methoxyphenyl)-2,2-dimethyl-3,4-
dihydropyrano[2,3-f ]chromen-10(2H)-one (1). To a solution of
compound 13 (195.5 mg, 0.47 mmol) in anhydrous MeOH (3.0 mL)
was added 3 N HCl (3.0 mL), and it was refluxed for 40 min under
N2. The mixture was cooled to room temperature, quenched with
water, and extracted 3 times with EtOAc (3 × 10 mL). The combined
organic layers were washed with brine, dried over MgSO4, and
concentrated in vacuo. The residue was purified by silica gel column
chromatography (n-hexane/EtOAc = 1:1) to produce the target
compound (127.4 mg, 73%) as an off-white solid. mp = 300−302 °C.
[α]D22 +5.4 (c 0.01, MeOH). IR (neat) νmax (cm−1): 3138.50 (>OH),
1738.40 (>CO). 1H NMR (400 MHz, DMSO-d6): δ 8.10 (s, 1H),
7.46 (d, J = 8.3 Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 6.45 (s, 1H), 5.21
(d, J = 4.6 Hz, 1H), 3.82 (s, 3H), 3.69 (q, J = 6.7 Hz, 1H), 2.81 (dd, J
= 17.2 and 5.5 Hz, 1H), 2.45 (dd, J = 16.8 and 7.3 Hz, 1H), 1.34 (s,
3H), 1.23 (s, 3H). 13C NMR (100 MHz, DMSO-d6): δ 173.99,
160.31, 159.14, 157.61, 154.59, 150.78, 130.75, 125.15, 124.69,
113.77, 108.01, 105.48, 93.98, 78.04, 67.27, 55.53, 26.48, 25.86, 20.91.
HRMS (ESI): m/z calculated for C21H21O6 [M + H]+, 369.1338;
found, 369.1333.
1-(2,6-Dihydroxy-4-(methoxymethoxy)-3-(3-methylbut-2-en-1-
yl)phenyl)ethanone (9). Compound 8 (2.70 g, 10.0 mmol) in MeOH
(50 mL) was cooled to 0 °C. Then, 2 N HCl (10 mL) was added
dropwise. After addition, the reaction mixture was warmed to 40 °C
and stirred for 3 h. The reaction was quenched with NaHCO3
(aqueous) and extracted with EtOAc (3 × 20 mL). The combined
organic layers were washed with brine, dried over MgSO4, and
concentrated under reduced pressure. The crude product was purified
by silica gel column chromatography (n-hexane/EtOAc = 8:1) to
produce compound 9 (2.16 g, 93%) as an off-white solid. mp = 112−
1
114 °C. H NMR (400 MHz, CDCl3): δ 6.18 (s, 1H), 5.20 (s, 2H),
5.18 (s, 1H), 3.47 (s, 3H), 3.35 (d, J = 7.2 Hz, 2H), 2.67 (s, 3H), 1.83
(s, 3H), 1.76 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 203.98,
161.39, 160.89, 160.60, 134.11, 121.92, 107.97, 105.86, 93.94, 93.90,
56.27, 32.99, 25.83, 21.63, 17.82. HRMS (ESI): m/z 281.1389
calculated for C15H21O5 [M + H]+, 281.1385.
1-(3,7-Dihydroxy-5-(methoxymethoxy)-2,2-dimethylchroman-8-
yl)ethanone (10). To a solution of compound 9 (2.16 g, 7.69 mmol)
in anhydrous DCM (30.0 mL) was added 75% m-CPBA (1.80 g, 7.80
mmol) at 0 °C, and the mixture was stirred for 20 min at room
temperature. After complete consumption of compound 9 (TLC),
montmorillonite K10 (2.1 g) was added and the mixture was further
stirred for 30 min at room temperature. The mixture was filtered and
washed with EtOAc. The organic layer was washed with saturated
Na2CO3 (aqueous), H2O, and brine, dried over MgSO4, and
concentrated in vacuo. The residue was purified by silica gel column
chromatography (n-hexane/EtOAc = 2:1) to produce compound 10
(1.61 g, 71%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 13.71
(s, 1H), 6.23 (s, 1H), 5.20 (s, 2H), 3.81 (q, J = 5.9 Hz, 1H), 3.48 (s,
3H), 2.86 (dd, J = 17.1 and 5.2 Hz, 1H), 2.65 (s, 3H), 2.62 (dd, J =
16.0 and 4.0 Hz, merged, 1H), 1.82 (d, J = 7.2 Hz, 1H), 1.42 (s, 3H),
1.39 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 203.41, 165.23, 161.20,
155.39, 106.48, 99.36, 94.64, 94.04, 78.36, 68.43, 56.45, 33.27, 25.91,
24.86, 21.91. HRMS (ESI): m/z calculated for C15H21O6 [M + H]+,
297.1338; found, 297.1325.
(E)-1-(3,7-Dihydroxy-5-(methoxymethoxy)-2,2-dimethylchro-
man-8-yl)-3-(dimethylamino)prop-2-en-1-one (11). Compound 10
(1.3 g, 4.39 mmol) was dissolved in DMF, and the solution was
warmed to 75 °C in an oil bath. DMF-DMA (0.7 mL, 5.26 mmol) was
then added dropwise to the flask. The mixture was stirred for 4.5 h
and then cooled to room temperature. The reaction was quenched
with H2O, and the mixture was extracted with EtOAc (3 × 10 mL).
The extracts were washed with H2O, dried, filtered, and concentrated
under reduced pressure to give a thick yellow oil that was purified by
General procedure for lipase-mediated enantioselective acylation of
rac-13: to a solution of rac-13 (100 mg) was added lipase (100 mg).
The suspension was stirred at room temperature. After a few minutes,
vinyl acetate (1 mL) was added and the reaction mixture was stirred
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J. Nat. Prod. 2021, 84, 1359−1365