5216
T. S. Lee et al. / Bioorg. Med. Chem. 15 (2007) 5207–5218
with various ratios of ethyl acetate and hexane as
solvent.
119.4, 118.5, 107.4, 56.6, 56.3, 52.3. ESI MS: 428.8
+
+
([M+1] ), 450.8 ([M+Na] ). HR-ESIMS: 451.1150
calcd for C H O Na: 451.1158).
(
2
6
20
6
1
.8.1. Wittig product 14. H NMR (400 MHz, CDCl ):
4
3
1
4.8.6. Wittig product 19. H NMR (500 MHz, CDCl ):
7
.89 (dd, J = 7.6, 1 Hz, 1H), 7.72 (s, 1H), 7.68 (t,
3
J = 7.6 Hz, 1H), 7.39 (dd, J = 17.2, 11.2 Hz, 1H), 7.34
dd, J = 7.6, 1 Hz, 1H), 5.42 (dd, J = 11.2, 1.2 Hz, 1H),
8.17 (d, J = 8.5 Hz, 1H), 8.03 (d, J = 7 Hz, 1H), 7.93
(dt, J = 8, 1 Hz, 1H), 7.86 (d, J = 16 Hz, 1H), 7.89–
7.82 (m, 2H), 7.79 (s, 1H), 7.70 (t, J = 7.5 Hz, 1H),
7.65(dd, J = 6.5, 1 Hz, 1H), 7.56 (t, J = 7.5 Hz, 2H),
7.51(dd, J = 8, 1.5 Hz, 1H), 7.48 (dd, J = 7, 1 Hz, 1H),
7.38 (d, J = 16.5 Hz, 1H), 7.35 (dd, J = 8.5, 1 Hz, 1H),
(
5
3
1
1
1
.32 (dd, J = 17, 1.2 Hz, 1H), 4.02 (s, 3H), 4.01 (s,
1
3
H), 3.86 (s, 3H). C NMR (100 MHz, CDCl3):
83.5, 182.8, 167.3, 160.2, 159.3, 141.2, 136.2, 135.5,
34.7, 134.5, 130.0, 126.5, 122.5, 119.4, 118.5, 117.5,
+
13
07.4, 56.6, 56.6, 52.7. ESI MS: 352.8 ([M+1] ), 374.8
4.07 (s, 3H), 4.02 (s, 3H), 3.78 (s, 3H). C NMR
(125 MHz, CDCl ): 189.2, 182.8, 162.5, 160.2, 159.4,
146.6, 135.8, 134.5, 133.9, 133.7, 131.4, 130.7, 130.4,
+
ꢁ
(
[M+Na] ), 351.7 ([Mꢁ1] ). HR-ESIMS: 375.0835
3
(
calcd for C H O Na: 375.0845).
6
2
0
16
130.2, 129.5, 128.6, 128.3, 126.9, 126.2, 126.0, 125.9,
125.8, 124.7, 124.1, 119.5, 118.6, 107.5, 56.8, 56.8,
1
.8.2. Wittig product 15. H NMR (500 MHz, CDCl ):
7.89 (dd, J = 8, 1 Hz, 1H), 7.69 (s, 1H) 7.67 (t,
J = 8.5 Hz, 1H), 7.34 (dd, J = 8.5, 1 Hz, 1H), 7.07
4
3
+
53.0. ESI MS: 478.9 ([M+1] ). HR-ESIMS: 501.1306
(calcd for C H O Na: 501.1314).
3
0
22
6
(
4
dt, J = 16, 7 Hz, 1H), 5.78 (dt, J = 16, 7 Hz, 1H),
1
3
.03 (s, 3H), 4.00 (s, 3H), 3.86 (s, 3H). C NMR
1
4.8.7. Wittig product 20. H NMR (500 MHz, CDCl ):
3
(
100 MHz, CDCl ): 183.7, 181.9, 169.4, 160.1, 155.0,
3
7.91(dd, J = 7.5, 1 Hz, 1H), 7.84 (d, J = 16.5 Hz, 1H),
7.79 (dd, J = 7.5, 1.5 Hz, 1H), 7.74 (s, 1H), 7.68 (t,
J = 7.5 Hz, 1H), 7.34 (d, J = 8.5 Hz, 1H), 7.23 (dd,
J = 7.5, 1.5 Hz, 1H), 7.05 (d, J = 16.5 Hz, 1H), 7.00 (t,
J = 7.5 Hz, 1H), 6.87 (d, J = 8 Hz, 1H), 5.95 (m, 1H),
5.15 (dd, J = 15, 2 Hz, 1H), 5.07 (dd, J = 10.5, 1 Hz,
1
1
1
41.3, 136.3, 135.6, 134.3, 130.4, 129.5, 127.6, 123.2,
20.2, 119.4, 118.5, 107.0, 56.6, 56.6, 52.5, 26.5,
3.8. ESI MS: 381.2 ([M+1] ), 403.2 ([M+Na] ).
+
+
HR-ESIMS: 403.1153 (calcd for C H O Na:
2
4
2
20
6
03.1158).
1H), 4.04 (t, J = 6.5 Hz, 2H), 4.03 (s, 3H), 4.01 (s,
3H), 3.81 (s, 3H), 2.60 (q, J = 7, 6.5 Hz, 2H).
1
.8.3. Wittig product 16. H NMR (500 MHz, CDCl ):
13
C
NMR (125 MHz, CDCl ): 189.9, 185.5, 168.4, 164.6,
4
3
7
.88 (dd, J = 8, 1 Hz, 1H), 7.68 (s, 1H) 7.67 (t,
3
J = 8 Hz, 1H), 7.34 (d, J = 8 Hz, 1H), 7.08 (d,
J = 16 Hz, 1H), 5.78 (dt, J = 16, 7 Hz, 1H), 4.02 (s,
160.1, 157.0, 156.4, 151.4, 134.6, 134.5, 134.4, 130.4,
129.0, 127.4, 127.3, 127.2, 122.3, 120.8, 120.5, 119.4,
118.5, 117.1, 111.9, 107.2, 67.9, 56.7, 56.6, 53.2, 33.8.
3
1
3
1
1
1
H), 4.00 (s, 3H), 3.86 (s, 3H), 2.24 (q, J = 7 Hz, 2H),
.49–1.41 (m, 2H), 1.39–1.25 (m, 6H) 0.89 (t, 7 Hz,
+
ESI MS: 498.9 ([M+1] ). HR-ESIMS: 521.1590 (calcd
for C H O Na: 521.1576).
1
3
H).
C NMR (100 MHz, CDCl ): 183.7, 182.9,
3
30 26
7
67.6, 160.0, 159.2, 141.2, 135.6, 135.1, 134.7, 134.3,
32.2, 130.2, 128.2, 126.9, 126.6, 122.9, 119.3, 118.5,
06.9, 56.7, 56.5, 52.5, 33.3, 32.2, 31.9, 29.4, 22.7, 14.2.
4.9. General procedure for methyl ester deprotection
+
+
ESI MS: 437.2 ([M+1] ), 459.2 ([M+Na] ). HR-ESIMS:
59.1791 (calcd for C H O Na: 459.1784).
To the ester dissolved in ethanol was added the same
volume of 2 N KOH aqueous solution dropwise at room
temperature. The reaction mixture was refluxed at 70 ꢁC
overnight and cooled down to room temperature. The
resulting solution was diluted with water, acidified to
pH 1 using 6 N HCl with vigorous stirring, and ex-
tracted with ethyl acetate. The organic phase was
washed with water, brine, and dried over sodium sulfate.
The solvent was removed in vacuo and the product was
purified by column chromatography using 5% methanol
in dichloromethane containing 1% acetic acid as eluent.
After the removal of solvent, the product was isolated as
yellow powder with around 80% yield.
4
2
6
28
6
1
.8.4. Wittig product 17. H NMR (500 MHz, CDCl ):
4
3
7
.89 (dd, J = 8, 1 Hz, 1H), 7.69 (s, 1H), 7.67 (t,
J = 8 Hz, 1H), 7.34 (dd, J = 8, 1 Hz, 1H), 7.10 (dt,
J = 11, 1 Hz, 1H), 5.79 (dt, J = 16, 6.5 Hz, 1H), 5.48
(
(
1
m, 2H), 4.03 (s, 3H), 4.00 (s, 3H), 3.86 (s, 3H), 2.30
m, 2H), 2.16 (m, 2H), 1.99 (m, 2H), 1.35 (m, 2H),
1
3
.27 (m, 2H), 0.88 (t, 6.5 Hz, 3H).
C NMR
(
125 MHz, CDCl ): 189.8, 181.1, 171.0, 164.9, 159.2,
3
1
1
5
4
36.4, 136.0, 134.7, 134.3, 131.1, 130.4, 129.4, 128.6,
26.6, 122.9, 119.4, 118.5, 112.9, 107.0, 56.7, 56.6,
2.5, 33.5, 32.7, 32.4, 31.5, 29.4, 22.7, 14.2. ESI MS:
+
1
4.9.1. Methyl ester deprotected compound 25. H NMR
76.9 ([M+1] ). HR-ESIMS: 499.2098 (calcd for
C H O Na: 499.2097).
32
(500 MHz, CDCl ): methyl ethers at 4.06 (s, 3H), 4.02
3
2
9
6
+
ꢁ
(
s, 3H). ESI MS: 484.8 ([M+1] ), 482.8 ([Mꢁ1] ). HR-
1
.8.5. Wittig product 18. H NMR (400 MHz, CDCl ):
.91(dd, J = 8, 1 Hz, 1H), 7.82 (d, J = 16.4 Hz, 1H),
.75 ( s, 1H), 7.69 (t, J = 8 Hz, 1H), 7.56 (d,
4
7
7
ESIMS: 507.1406 (calcd for C H O Na: 507.1420).
29 24
3
7
4.10. General procedure for methyl deprotection with
BBr3
J = 7.2 Hz, 2H), 7.37 (t, J = 7.2 Hz, 2H), 7.35 (d,
J = 8 Hz, 1H), 7.28 (t, J = 7.2 Hz, 1H), 6.66 (d,
J = 16.4 Hz,1H), 4.04(s, 3H), 4.01(s, 3H), 3.79(s, 3H).
The methyl-protected starting material was dissolved in
dry dichloromethane and was cooled down to ꢁ78 ꢁC.
To this, 3–5 equivalents of boron tribromide was slowly
added using microsyringe and the reaction mixture was
1
3
C NMR (125 MHz, DMSO-d ): 182.6, 181.6, 166.5,
6
1
1
59.5, 158.5 138.8, 136.7, 135.2, 134.9, 134.0, 133.1,
33.1, 129.1, 128.0, 127.7, 126.5, 126.5, 126.3, 121.7,