Synthesis of Cynandione B Analogues
63
7
2
-Methoxy-6-methyl-6H-benzo[c]chromen-6-ol 15 and
’-(2-hydroxypropan-2-yl)-3 -methoxybiphenyl-2-ol 16
acetone to give 23 (165 mg, 49 %) as pale yellow crystals, mp
1
255–2578C. H NMR (500 MHz, [D6]DMSO) d 7.01 (1H, d,
0
J 8.9 Hz), 7.39 (3H, m), 7.51 (1H, m), 9.11 (1H, d, J 8.2 Hz),
1
To lactone 14 (50 mg, 0.22 mmol) in THF (2.5 mL) at 08C
under nitrogen was added MeMgBr (3M in Et O, 0.30 mL,
0.90 mmol) dropwise. The reaction was allowed to stir at 08C
for 30 min, then at room temperature for 2 h. 2 M HCl was then
1
3
1.08 (1H, br s). C NMR (125 MHz, [D6]DMSO) d 105.7 (C),
2
1
(
1
16.8 (CH), 117.2 (CH), 118.5 (C), 119.0 (C), 125.1 (CH), 126.4
CH), 128.3 (CH), 129.6 (CH), 147.6 (C), 149.4 (C), 154.8 (C),
ꢀ
1
65.4 (C). nmax(neat)/cm 3359, 3199, 1656, 1590, 1436, 1185.
added and the product extracted with CHCl (3 ꢂ 5 mL). The
3
þ
LRMS (ESI) m/z 229 ([MþH] , 100 %), 227 (90). HRMS (ESI)
combined organic layers were dried (MgSO ), concentrated
4
þ
found 229.0495, C H O [MþH] requires 229.0495.
13 9 4
under vacuum then purified via flash chromatography (CHCl3 :
THF 95 : 5) to yield the lactol 15 as a colourless oil (20 mg,
3
1
7 %) and the diol 16 as a colourless solid (17 mg, 30 %), mp
52–1558C.
Benzochromenol 15 data: H NMR (500 MHz, CDCl3)
Spiro-dimer 24
1
To lactone 23 (50 mg, 0.22 mmol) in THF (10 mL) at 08C
under nitrogen was added MeMgBr (3 M in Et O, 0.45 mL,
.35 mmol) dropwise. The reaction was allowed to stir at 08C for
5 min, then at room temperature for 24 h. 2 M HCl was then
added and the product extracted with CHCl
combined organic layers were dried (MgSO ) then concentrated
under vacuum. The crude product in a mixture of CHCl (4 mL)
3
and 2 M HCl (0.5 mL) was then stirred vigorously at room
temperature overnight. The mixture was diluted with water
2
d 1.90 (3H, s), 3.94 (3H, s), 4.56 (1H, s), 6.92 (1H, dd, J 8.0,
1
1
1
7
.0 Hz), 7.04 (2H, m), 7.26 (1H, m), 7.39 (1H, dd, J 8.1, 8.1 Hz),
.44 (1H, dd, J 8.1, 1.1 Hz), 7.72 (1H, dd, J 8.5, 1.3 Hz).
ꢀ
1
3
(4 ꢂ 5 mL). The
nmax(neat)/cm 3428, 2936, 1596, 1464, 1428, 1256, 1069,
1
2
þ
4
054, 1019. GCMS (R 27.69 min) m/z 224 ([M-H O] , 64 %),
09 (100), 165 (49), 152 (27).
t
2
1
Diol 16 data: H NMR (500 MHz, CDCl ) d 1.30 (3H, s), 1.46
3
(3H, s), 3.98 (3H, s), 4.59 (1H, br s), 4.82 (1H, br s), 6.76 (1H,
m), 6.92 (2H, m), 7.03 (2H, m), 7.25 (1H, m), 7.28 (1H, m).
1
3
and the product extracted with CHCl
(MgSO ), concentrated under vacuum then purified via flash
chromatography (CHCl : EtOAc 95 : 5) to yield the starting
3
(3 ꢂ 5 mL), dried
C
NMR (125 MHz, CDCl ) d 29.9 (CH ), 31.2 (CH ), 55.8 (CH ),
4
3
3
3
3
3
7
1
4.5 (C), 112.1 (CH), 115.4 (CH), 120.0 (CH), 125.8 (CH),
27.6 (CH), 129.0 (CH), 129.6 (CH), 130.7 (C), 134.6 (C), 136.3
lactone 23 (24 mg, 48 %) and spiroacetal 24 as a colourless
solid (12 mg, 24 %). A small sample was recrystallized from
CH Cl : hexane to obtain crystals suitable for X-ray crystal
ꢀ
1
(C), 152.4 (C), 158.1 (C). nmax(neat)/cm 3191, 2943, 1444,
2
2
1
359, 1248, 1155, 1089, 1018. GCMS (R 26.39 min) m/z 240
þ
t
1
analysis, mp 200–2058C (dec.). H NMR (500 MHz, [D6]ace-
tone) d 1.78 (3H, s), 2.74 (1H, d, J 14.0 Hz), 3.69 (1H, d, J
4.0 Hz), 6.65 (1H, d, J 8.8 Hz), 6.83 (1H, d, J 8.8 Hz), 6.88 (1H,
([M-H O] , 12 %), 225 (100), 210 (20). HRMS (ESI) found
2
þ
2
81.1148, C H NaO [MþNa] requires 281.1148.
1
6
18
3
1
d, J 8.8 Hz), 6.92 (1H, dd, J 8.1, 1.1 Hz), 6.93 (1H, dd, J 8.0,
1.1 Hz), 6.98 (1H, d, J 8.8 Hz), 7.04 (1H, m), 7.07 (1H, m), 7.20–
7
-Methoxy-6,6-dimethyl-6H-benzo[c]chromene 17
To diol 16 (15 mg, 0.06 mmol) in benzene (0.5 mL) at room
temperature was added BF .Et O (10 mL, 0.08 mmol). The
7
.24 (2H, m), 8.08 (1H, br s), 8.60 (1H, dd, J 8.0, 1.6 Hz), 8.67
13
(1H, br s), 8.68 (1H, br s), 8.78 (1H, dd, J 8.2, 1.6 Hz). C NMR
125 MHz, [D6]acetone) d 25.2, 41.4, 72.7, 101.4, 115.6, 117.4,
3
2
(
reaction was allowed to stir at room temperature for 5 min then
diluted with water (3 mL) and extracted with EtOAc (3 ꢂ 5 mL).
1
1
1
1
17.8, 118.0, 118.2, 118.3, 118.5, 119.0, 121.6, 122.0, 122.2,
22.6, 123.7, 129.2, 129.4, 129.5, 143.4, 147.9, 148.6, 149.5,
The combined organic layers were dried (MgSO ), concentrated
4
ꢀ
1
50.6, 152.9; (2 signals obscured). nmax(neat)/cm 3375, 2921,
under vacuum then purified via flash chromatography (EtOAc :
petrol 1 : 1) to yield the benzopyran 17 as a colourless oil
1
12 mg, 86 %). H NMR (500 MHz, CDCl ) d 1.72 (6H, s),
.85 (3H, s), 6.86 (1H, dd, J 8.2, 1.0 Hz), 6.91 (1H, dd, J 8.1,
.2 Hz), 6.98 (1H, m), 7.20 (1H, m), 7.29 (1H, m), 7.37 (1H, dd,
J 7.9, 1.1 Hz), 7.64 (1H, dd, J 7.9, 1.6 Hz). C NMR (125 MHz,
CDCl ) d 27.5 (CH ), 55.4 (CH ), 78.3 (C), 110.9 (CH), 114.9
CH), 117.8 (CH), 121.2 (CH), 121.9 (C), 123.4 (CH), 128.1 (C),
28.3 (CH), 129.3 (CH), 130.5 (C), 152.7 (C), 155.7 (C).
nmax(neat)/cm 2932, 1594, 1464, 1427, 1267, 1253, 1085,
þ
471, 1429, 1228. LRMS (ESI) m/z 453 ([MþH] , 5 %), 227
þ
(100). HRMS (ESI) found 453.1334, C H O [MþH]
28 21 6
(
3
requires 453.1333.
3
1
1
3
Supplementary Material
3
3
3
1
13
H and C NMR spectra for compounds 9, 13, 16, 17, 23 and 24
(
are available from the Journal’s website. Crystallographic
information files for 13 and 24 have been deposited with the
Cambridge Crystallographic Data Centre and assigned the
1
ꢀ
1
þ
1
022. GCMS (R 25.12 min) m/z 240 ([M] , 15 %), 225 (100),
þ
t
2
requires 241.1223.
10 (24). HRMS (ESI) found 241.1223, C H O [MþH]
1
6 17 2
7
,10-Dihydroxy-6H-benzo[c]chromen-6-one 23
Acknowledgements
To hydroquinone 21 (0.25 g, 1.49 mmol) in diethyl ether
5 mL) was added MgSO (0.52 g, 4.32 mmol) and silver(I)
oxide (0.85 g, 3.67 mmol). The reaction was stirred for 2 h in
the dark and then filtered, washed with chloroform (10 mL) and
concentrated under vacuum to give crude quinone 22 as an
orange oil. The quinone 22 in CH Cl (2 mL) was added
Financial support from the Australian Research Council through the Centres
of Excellenceprogram is gratefully acknowledged. Professor Carl Schiesser,
The University of Melbourne, is acknowledged for useful discussions.
(
4
2
2
References
dropwise to a solution of phenol (140 mg, 1.49 mmol) and
trifluoroacetic acid (0.1 mL) in CH Cl (1 mL) and the mixture
was stirred at room temperature for 4 h. After removal of solvent
under vacuum the residual solid was recrystallized from
[
1] G. W. Burton, K. U. Ingold, Acc. Chem. Res. 1986, 19, 194.
2
2
doi:10.1021/AR00127A001
[2] C.-N. Lin, P.-L. Huang, C.-M. Lu, M.-H. Yen, R.-R. Wu, Phytochem-
istry 1997, 44, 1359. doi:10.1016/S0031-9422(96)00695-4