1
658
N. J. Lawrence et al.
PAPER
FAB-MS m/z calcd for C H O : (M ) 316.1311, found 316.1313.
+
Recrystallisation (EtOAc) gave the 4 (0.74 g, 97%) mp 170–172 °C;
1
8
20
5
R = 0.53 (SiO , EtOAc).
+
f
2
FAB-MS m/z (%) 316 ([M+H] , 100).
IR (KBr) n = 3000–2700 (m), 1440 (s), 1250 (s), 1190 (s), 1000 (s)
-
1
cm .
1
2
-Hydroxy-3,5,6,7-tetramethoxyphenanthrene (6)
Anhyd N was passed through a solution containing stilbene E-1
H NMR (300 MHz; CDCl ): d = 3.6 (2H, d, J = 14.4 Hz, CH2),
.64 (6H, s, 3,5-OMe), 3.78 (3H, s, 4-OMe), 6.24 (2H, s, H-2, H-6),
.45–7.54 (6H, m, aromatic), 7.71–7.73 (4H, m, aromatic).
2
3
PH
(
(
0.05 g, 0.16 mmol), iodine (0.02 g, 0.16 mmol), propylene oxide
6.3 mL, 90 mmol) and benzene (500 mL) for 20 min. The solution
3
7
was irradiated using a 125W UV lamp for approximately 3 h until
the reaction was complete (TLC). The solution was washed with
Na S O (50 mL, aq, 15%), H O (50 mL ) and brine (50 mL). The
Anal calcd for C H O P: C, 69.1; H, 6.1; P, 8.1; found C, 68.8; H,
.9; P, 7.9.
22
23
4
5
2
2
5
2
+
FAB-MS m/z (%) 383 ([M+H] , 80), 181 (100).
organic extract was dried (MgSO ) and evaporated to give a yellow
4
solid. Chromatography (silica gel, 2:1 hexane:EtOAc) gave an off-
1
0
white solid (0.033 g, 68%), mp 175–177 °C (lit. mp 176–178 °C);
R = 0.69 (SiO , 2:1 hexane:EtOAc).
(
E)-1-(3’,4’,5’-Trimethoxyphenyl)-2-(4’’-methoxy-3’’-tert-bu-
tyldimethylsiloxyphenyl)ethene[(E)-5]
f
2
To compound 4 (1.70 g, 4.44 mmol) in anhyd THF (8 mL) was
slowly added BuLi [2.8 mL, 4.44 mmol (1.6 M solution)] at 0 °C.
The red solution was stirred for 15 min at 0 °C before 4-methoxy-
IR (KBr) n= 3440 (br, OH), 3000–2740 (m), 1480–1460 (m), 1280
-1
(
s), 1270–1210 (s), 1170–1120 (d) cm .
1H NMR (300 MHz; CDCl
): d = 4.01 (3H, s, OCH
OCH ), 4.04 (3H, s, OCH ), 4.10 (3H, s, OCH ), 5.88 (1H, s, OH),
1
5
3
), 4.02 (3H, s,
3
3
-(tert-butyl-dimethylsiloxy)benzaldehyde (1.0 g, 3.70 mmol) in
3
3
3
anhyd THF (10 mL) was added. The solution was stirred for an ad-
ditional 30 min at 0 °C, allowed to slowly warm to r.t. and stirred
overnight to afford a white precipitate of lithium diphenylphosphi-
7
7
.08 (1H, s, H-1), 7.31 (1H, s, H-8), 7.51 (1H, d, J = 6.3 Hz, H-10),
.53 (1H, d, J = 6.3 Hz, H-9), 9.07 (1H, s, H-4).
1
3
nate. The mixture was treated with H O (20 mL) and extracted with
C NMR (75.5 MHz; CDCl ): d = 55.8, 55.9, 60.3, 61.3, 105.3,
2
3
CHCl (3 x 30 mL). The organic extracts were dried (MgSO ) and
107.1, 111.2, 118.7, 124.0, 124.9, 126.2, 127.7, 129.3, 142.5, 144.6,
146.7, 151.5, 151.7.
3
4
evaporated in vacuo. Chromatography (silica gel, hexane:EtOAc
2
8
:1 v/v) and recrystallisation (EtOH) gave white crystals (1.28 g,
Anal calcd for C H O : C, 68.8; H, 5.7; found C, 68.5; H, 5.4.
1
8
18 18
5
0%), mp 127–128 °C (lit. mp 128–130 °C); R = 0.75 (SiO , hex-
f
2
+
FAB-MS m/z (%) 314 ([M+H] , 100).
ane:EtOAc 2:1 v/v).
IR (KBr) n= 3060 (w), 2930 (m), 1590 (s), 1390 (w), 1350 (s), 1280
1
9
5
-Iodo-2-methoxyphenol (9)
-
1
(
s), 1130 (s), 1010-990 (m), 970 (s) cm .
2
0
Guaicol acetate (12 g, 72 mmol), Ac O (3.6 mL, 38 mmol) and
HgO (12 g, 55 mmol) in CH Cl (40 mL) were heated under reflux
and I (24 g, 95 mmol) was added portionwise slowly over 3 h. Each
portion of iodine was added only after the orange colour of the re-
action mixture reemerged. The resulting pink mixture was heated
under reflux for further 12 h before being cooled and filtered. The
2
1
H NMR (300 MHz; CDCl ): d = 0.19 (6H, s, SiMe ), 1.02 (9H, s,
3
3
2
2
CMe ), 3.83 (3H, s, OMe), 3.86 (3H, s, OMe), 3.92 (6H, s, 2 x
3
2
OMe), 6.71 (2H, s, H-2',6'), 6.83 (1H, d, J = 8.6 Hz, H-5''), 6.84 (1H,
d, J = 17.3 Hz, CH=C), 6.92 (1H, d, J = 17.3 Hz, C=CH), 7.07–7.03
(2H, m, H-2,'' H-4'').
1
3
solid residue obtained was washed thoroughly with H O. The fil-
C NMR (75.5 MHz; CDCl ): d = -4.6, 16.5, 25.8, 55.5, 56.1, 61.0,
2
3
trate was washed with Na S O (aq, sat.) and H O (30 mL). The or-
1
1
03.3, 112.0, 118.6, 120.5, 126.6, 127.9, 130.4, 132.6, 135.4, 145.2,
50.9, 153.4.
2
2
5
2
ganic layer was dried (MgSO ) and concentrated in vacuo. The
4
brown residue obtained was recrystallised (MeOH) to yield off-
white crystals. These crystals were treated with NaOH (10 mL, aq
30% w/v) and heated under reflux. The boiling solution was acidi-
fied to pH 1 with concd HCl and allowed to cool. The precipitate
which formed was filtered, washed with ice-cold water and recrys-
tallised (MeOH) to give the phenol 9 as white crystals (14.2 g, 79%)
Anal calcd for C H O Si C, 66.9; H, 8.0; Si, 6.5; found C, 67.2; H,
24
34
5
7
.9; Si, 6.5.
+
FAB-MS m/z (%) 430 ([M+H] , 100).
2
1
mp 88–90 °C (lit. mp 87–88 °C); R = 0.81 (SiO , EtOAc:hexane
f
2
trans-Combretastatin-A4 [(E)-1].
To alkene E-5 (103 mg, 0.24 mmol) in anhyd THF, was added
TBAF (2 mL of 0.5 M solution in THF, 1 mmol). The yellow solu-
1
:2).
IR (KBr) n = 3500–3400 (br), 3000–2740 (m), 1300 (s), 1220 (s),
-
1
1
130 (m) cm .
tion was stirred for 20 min and then treated with H O (50 mL). The
2
mixture was extracted with CHCl (3 x 25 mL), and the organic ex-
1
3
H NMR (300 MHz; CDCl ): d = 3.86 (3H, s, OMe), 5.61 (1H, s,
3
tracts washed with H O (2 x 25 mL), dried (MgSO ) and concen-
2
4
OH), 6.59 (1H, d, J = 8.5 Hz, H-3), 7.16 (1H, dd, J = 8.5, 2.1 Hz, H-
trated in vacuo. Chromatography (silica gel, EtOAc:hexane, 1:1 v/
4
), 7.24 (1H, d, J = 2.1 Hz, H-6).
1
8
v) gave an off white solid (73 mg, 96%) mp 115–116 °C (lit. mp
16 °C); R = 0.48 (SiO , EtOAc:hexane, 1:1 v/v).
1
3
C NMR (75.5 MHz; CDCl ): d = 56.1, 83.1, 112.6, 123.5, 129.1,
3
1
f
2
1
46.6, 146.8.
-
1
IR (KBr) n = 3440 (br), 960 (trans-HC=CH) cm .
UV (MeCN): lmax (e) 222 (23 416), 330 nm (34 745).
Anal calcd for C H O I: C, 33.6; H, 2.8; found C, 33.7; H, 2.7.
7
7
2
+
FAB-MS m/z (%) 250 ( [M+H] , 100).
1
H NMR (300 MHz; CDCl ): d = 3.68 (3H, s, OCH ), 3.86 (3H, s,
3
3
OCH ), 3.92 (6H, s, OCH ), 5.61 (1H, s, OH), 6.71 (2H, s, 2',6'-H),
,1-Dibromo-2-(3’,4’,5’-trimethoxyphenyl)ethene22 (7)
3
3
1
6
6
.83 (1H, d, J = 8.3 Hz, 5''-H), 6.87 (1H, d, J = 16.6 Hz, CH=C),
.92 (1H, d, J = 16.6 Hz, C=CH), 6.98 (1H, dd, J = 8.3, 2.0 Hz, 6''-
Triphenylphosphine (3.16 g, 12.06 mmol) was added to CBr (2 g,
4
6
6
.03 mmol) in anhyd CH Cl (45 mL) at 0 °C. Compund 2 (1.18 g,
.03 mmol) was added and the resulting mixture was stirred at 0 °C
2 2
H), 7.14 (1H, d, J = 2.0 Hz, 2''-H).
1
3
C NMR (75.5 MHz; CDCl ): d = 55.9, 56.0, 60.9, 103.3, 111.6,
for 10 min before the addition of H O (15 mL). The organic phase
3
2
1
14.2, 119.1, 127.0, 127.7, 133.2, 137.6, 144.7, 145.7, 146.3, 153.3.
was separated, dried (MgSO ) and concentrated in vacuo. The yel-
4
low slurry obtained was tritrated with hexane and then Et O to re-
2
Anal calcd for C H O : C, 68.3; H, 6.4; found C, 68.9, H, 6.6.
18
20
5
move Ph PO. The organic washings were dried (MgSO ) and
3
4
concentrated in vacuo to give the dibromoalkene (2.12 g, 65%) as a
Synthesis 1999, No. 9, 1656–1660 ISSN 0039-7881 © Thieme Stuttgart · New York