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RSC Advances
Page 8 of 12
DOI: 10.1039/C6RA18806K
ARTICLE
Journal Name
mixture was stirred at room temperature for 8 h, then poured 108.5, 107.4, 99.0, 80.9, 62.3, 56.0, 55.2, 38.2, 24.1, 13.99,
onto ice water (200 mL). The resulting aqueous layer was 13.7. GCꢀMS m/z (relative intensity): 360(M+, 0.9), 281(0.2),
extracted with EtOAc (3 x 100 mL). The extract was washed 259(0.1), 207(0.7), 151(100), 135(0.2), 123(0.9), 109(0.6),
with water, dried over MgSO4, and concentrated under vacuum. 92(0.2), 77(0.3), 65(0.2), 52(0.1).
The residue was subjected to column chromatography on silica
1
gel (EtOAc:hexane 3:7) to yield
8
(3.64 g, 9.7 mmol, 74%). H
Oxidation Reactions:
NMR (400 MHz, CDCl3): δ 7.83 (dd, J1=8.5, J2=2.2 Hz, 1H), δ
7.62 (d, J=2.1 Hz, 1H), δ 6.94ꢀ6.87 (m, 3H), δ 6.83ꢀ6.77 (m,
2H), δ 5.63 (s, 1H, Cβ), δ 4.28 (q, J=6.9 Hz, 2H), ), δ 3.94 (s,
Oxidation of 1 withTPPFeCl. Mixtures of 1 (100 mg, 0.47 mmol),
TPPFeCl (4.3 mg, 0.0047 mmol), tꢀBuOOH (70% aq solution, 64
ꢁL, 0.47 mmol), and 0.1N phosphate buffer, pH 3 (3 mL) in three
different solvents [1.0 mL CH3CN (A), 1.05 g [C4C1im]Cl (B), and
0.9 g [P4444]Cl (C)] were stirred at 25ºC for 14 h. The mixtures
were extracted separately with EtOAc (3 x 10 mL) and each set of
combined extracts was washed with saturated aq. NaCl solution,
then dried over MgSO4. After evaporating the solvent under vacuum,
each of the resulting residues was subjected to column
chromatography on silica gel (EtOAc:hexanes 1:5) to give 1A (58.2
mg, 0.27 mmol, 58%) and 10A (40.2 mg, 0.19 mmol, 41%); 1B (67
mg, 0.31 mmol, 67%) and 10B (28 mg, 0.13 mmol, 28 %) and 1C
(50 mg, 0.23 mmol, 50%) and 10C (46.5 mg, 0.22 mmol, 47 %).
3H), δ 3.91 (s, 3H), δ 3.74 (s, 3H), δ 1.24 (t, J=7.3 Hz, 3H). 13
C
NMR (400 MHz, CDCl3): δ 190.0 (Cα), 167.1 (Cγ), 155.0,
154.2, 151.0, 149.0, 126.9, 124.8, 116.8, 114.7, 111.3, 110.1,
82.3 (Cβ), 62.2, 56.0, 55.9, 55.6 14.0. GCꢀMS m/z (relative
intensity): 374 (M+, 8), 301(1) 273 (2), 165 (100), 151(2),
137(4), 123(5), 107(2), 92(4), 77(5), 64(1), 51(1).
Preparation of 5. A solution of
9 (1.0 g, 2.78 mmol) in THF
(25 mL) and H2O (2.5 mL) was stirred at room temperature43.
Sodium borohydride (1.06 g, 27.8 mmol) was added over 3 h
and the solution was further stirred for 24 h at room
temperature. The reaction mixture was quenched with a
saturated solution of ammonium chloride, (15 mL) and was
then concentrated under vacuum. The residue was diluted with
water (100 mL) and extracted with dichloromethane (3 × 50
mL). The solvent was evaporated under vacuum, and the
residue was subjected to column chromatography on silica gel
Oxidation of 2 withTPPFeCl. Mixtures of 2 (100 mg, 0.31 mmol),
TPPFeCl (2.9 mg, 0.0031 mmol), tꢀBuOOH (70% aq solution, 43
ꢁL, 0.31 mmol), and 0.1N phosphate buffer, pH 3 (3 mL) in three
different solvents [1.0 mL CH3CN (A), 1.05 g [C4C1im]Cl (B), and
0.9 g [P4444]Cl (C)] were stirred at 25ºC for 14 h. The mixtures
were extracted separately with ethyl acetate (3 x 10 mL) and each set
of combined extracts was washed with saturated aq. NaCl solution,
then dried over MgSO4. After evaporating the solvent under vacuum,
each of the resulting residues was subjected to column
chromatography on silica gel (EtOAc:hexanes 1:3) to give 2A (68
mg, 0.22 mmol, 68%) and 11A (22 mg, 0.07 mmol, 22%); 2B (72
mg, 0.23 mmol, 72%) and 11B (9.4 mg, 0.03 mmol, 9.5%); and 2C
(58 mg, 0.18 mmol, 58%) and 11C (25.2 mg, 0.08 mmol, 25%).
(EtOAc:hexane 1:1) to produce
5 (0.683 g, 2.13 mmol, 77%).
1H NMR (400 MHz, CDCl3, mixture of diastereomers): δ 7.0ꢀ
6.76 (m, 7H), δ 4.99ꢀ4.92 (m, 1H, Cα), δ 4.25ꢀ4.19 (m, 1H, Cβ),
δ 3.95ꢀ3.51 (m, 2H, Cγ), δ 3.87, 3.86, 3.77, 3.75 (s, 6H). 13C
NMR (400 MHz, CDCl3, mixture of diastereomers): δ 154.7,
152.1, 151.7, 151.6, 146.7, 146.6, 145.5, 145.2, 132.5, 131.8,
119.9, 119.3, 118.3, 118.1, 114.8, 114.7, 114.4, 114.3, 109.5,
109.0, 84.4, 83.5, 73.8, 73.7, 61.4, 61.0, 55.9, 55.7. GCꢀMS
m/z (relative intensity): Major diastereomer: 302(M+ꢀ18, 0.4),
284(2), 272(100), 255(0.8), 243(2.8), 211(1.3), 183(1.7),
149(1.3), 133(1.5), 124(1.6), 109(1.5), 89(1.0), 77(1.4), 63(0.6),
51(0.6). Minor diastereomer: 302(M+ꢀ18, 0.4), 284(84),
272(87), 253(18), 243(51), 225(14), 207(45), 197(11), 183(13),
169(3), 161(29), 149(33), 137(34), 124(100), 109(79), 89(24),
77(39), 63(19), 53(16). HRMS (ESI) m/z [M+Na]+ calcd for
C17H20O6Na 343.1152, found 343.1152.
Oxidation of 4 withTPPFeCl. Mixtures of
mmol), TPPFeCl (4.3 mg, 0.0047 mmol), ꢀBuOOH (70% aq
solution, 64 ꢁL, 0.47 mmol), and 0.1N phosphate buffer, pH 3
(3 mL) in three different solvents [1.0 mL CH3CN ( ), 1.05 g
[C4C1im]Cl ( ), and 0.9 g [P4444]Cl ( )] were stirred at 25ºC
4 (100 mg, 0.47
t
A
B
C
for 14 h. The mixtures were extracted separately with ethyl
acetate (3 x 10 mL) and each set of combined extracts was
washed with saturated aq. NaCl solution, then dried over
MgSO4. After evaporating the solvent under vacuum, each of
the resulting residues was subjected to column chromatography
on silica gel (EtOAc:hexanes 1:5) to give 4A (55 mg, 0.16
mmol, 55%) and 12A (37 mg, 0.11 mmol, 38%); 4B(69 mg,
0.21 mmol, 69%) and 12B (21.5 mg, 0.07 mmol; 22%) and 4C
(64 mg, 0.19 mmol, 64%) and 12C(30 mg, 0.09 mmol, 30%).
1H NMR (400 MHz, CDCl3): δ 7.75 (dd, J1=8.4, J2=2.0 Hz,
1H), δ 7.57 (d, J=2.0 Hz, 1H), δ 6.88 (d, J=8.5 Hz, 1H), δ
6.87ꢀ6.75 (m, 4H), δ 5.43 (dd, J1=6.1, J2=4.2 Hz, 1H), δ 4.17ꢀ
4.04 (m, 2H), ), δ 3.94 (s, 3H), δ 3.89 (s, 3H), δ 3.73 (s, 3H).
13C NMR (400 MHz, CDCl3): δ 195.3, 154.6, 154.1, 151.4,
149.2, 127.9, 123.6, 116.6, 114.8, 110.8, 110.1, 82.0, 63.6,
56.1, 55.9, 55.6. GCꢀMS m/z (relative intensity): 314(M+ꢀ18,
1.0), 302(25), 284(1.0), 207(0.5), 165(100), 151(8), 137(5),
123(5), 107(5), 92(4), 77(7), 65(2), 51(2). HRMS (ESI) m/z
[M+H]+ calcd for C18H21O6 333.1333, found 333.1332.
Preparation of 9. In three separate oneꢀneck round bottom
flasks were placed NaH (60 % dispersion in mineral oil (1.12 g,
28.12 mmol),
7 (4.95 g, 15.62 mmol) and 4ꢀmethoxyphenol
(3.96 g, 31.24 mmol)43. The flasks were purged with N2 for 15
min after which 5.5 mL THF and 20.5 mL DMF were added to
each. The solution of NaH in THF/DMF was cooled to 0° C
and the solution of 4ꢀmethoxyphenol was added. The mixture
was stirred at room temperature for 1 h and then cooled to 0° C
again. The solution of
7 was added, and the resulting mixture
was stirred at room temperature for 8 h, then poured onto ice
water (120 mL). The resulting aqueous layer was extracted with
EtOAc (3 x 60 mL). The extract was washed with water, dried
over MgSO4, and concentrated under vacuum. The residue was
subjected to column chromatography on silica gel
(EtOAc:hexane 3:7) to yield
9
(1.0 g, 2.8 mmol, 18%). 1H
NMR (400 MHz, CDCl3): δ 7.76 (dd, J1=8.4, J2=2.0 Hz, 1H), δ
7.63 (d, J=2.0 Hz, 1H), δ 6.94 (d, J=8.5 Hz, 1H), δ 6.93ꢀ6.88
(m, 2H), δ 6.83ꢀ6.76 (m, 2H), 5.62 (s, 1H, Cβ), δ 4.28 (q, J=7.2
Hz, 2H), δ 3.92 (s, 3H), δ 3.74 (s, 3H), δ 1.23 (t, J=7.1 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 189.8(Cα), 167.0(Cγ), 160.7,
157.8, 151.6, 146.7, 145.4, 126.6, 125.4, 114.2, 114.2, 111.3,
Oxidation of 13 with TPPFeCl. Mixtures of 13 (50 mg, 0.195
mmol), TPPFeCl (5 mg, 0.005 mmol), tꢀBuOOH (70% aq solution,
27 ꢁL, 0.47 mmol), and 0.1N phosphate buffer, pH 3 (1.5 mL) in
three different solvents [0.5 mL CH3CN (A), 0.2 g [C4C1im]Cl (B),
and 0.2 g [P4444]Cl (C)] were stirred at 25ºC for 14 h. The mixtures
were extracted separately with EtOAc (3 x 5 mL) and each set of
8 | J. Name., 2012, 00, 1-3
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