Gambierol Analogues
4894 – 4909
1.39 (s, 3H), 1.31 (s, 3H), 1.27 (s, 3H), 1.18 (s, 9H), 1.13 (s, 3H), 1.12 (s,
3H), 0.94 (s, 9H), 0.11 (s, 3H), 0.07 ppm (s, 3H); 13C NMR (125 MHz,
C6D6): d=139.3, 136.0, 134.4, 132.8, 131.1, 129.9, 128.5, 113.0, 85.1, 84.2,
83.5, 82.7, 82.5, 80.2, 79.9, 79.7, 78.9, 78.6, 77.1, 76.1, 74.5, 73.7, 72.8, 72.5,
72.3, 64.2, 54.5, 44.7, 38.9, 38.2, 32.5, 32.4, 30.4, 29.2, 29.0, 28.4, 27.1, 26.0,
24.7, 22.2, 22.0, 20.8, 19.4, 18.3, 18.2, 15.7, ꢀ1.8, ꢀ2.1 ppm; HRMS
(FAB): m/z calcd for C60H8979BrO10Si2Na [M++Na]: 1127.5075; found:
1127.5110; calcd for C60H8981BrO10Si2Na [M++Na]: 1129.5073; found:
1129.5061.
3.58 (ddd, J=10.9, 9.7, 5.2 Hz, 1H), 3.42–3.32 (m, 4H), 3.23 (dd, J=12.0,
2.9 Hz, 1H), 3.14–3.05 (m, 3H), 3.02 (dd, J=13.2, 3.4 Hz, 1H), 2.42 (ddd,
J=12.0, 4.6, 4.0 Hz, 1H), 2.35–2.28 (m, 2H), 2.14 (m, 1H), 2.10–1.94 (m,
6H), 1.77–1.36 (m, 11H), 1.39 (s, 3H), 1.30 (s, 3H), 1.24 (s, 3H), 1.12 (s,
3H), 1.10 (s, 3H), 1.00 (s, 9H), 0.94 (s, 9H), 0.14 (s, 3H), 0.11 (s, 3H),
0.07 (s, 3H), 0.06 ppm (s, 3H); 13C NMR (125 MHz, C6D6): d=139.3,
132.8, 131.1, 112.9, 85.1,84.2, 82.8, 82.5, 80.3, 79.9, 79.7, 78.6, 77.7, 76.1,
75.9, 74.9, 74.5, 74.1, 72.6, 72.5 (2), 72.3, 62.7, 54.5, 44.3, 39.1, 38.1, 32.8,
32.4, 29.7, 29.0, 27.8, 26.1, 26.0, 24.7, 22.2, 22.0, 21.4, 18.4, 18.31, 18.27,
15.7, ꢀ1.8, ꢀ2.1, ꢀ4.0, ꢀ4.9 ppm; HRMS (FAB): m/z calcd for
C50H8579BrO11Si2Na [M++Na]: 1019.4712; found: 1019.4726; calcd for
C50H8581BrO11Si2Na [M++Na]: 1021.4705; found: 1021.4711.
HF·pyridine (0.2 mL) was added to a solution of the above (Z)-vinyl bro-
mide (7.3 mg, 0.0064 mmol) in THF (0.6 mL) cooled to 08C. The result-
ing mixture was stirred at room temperature for 4 days and then poured
into cold saturated aqueous NaHCO3. The aqueous layer was extracted
several times with CHCl3. The combined organic layers were dried over
Na2SO4, filtered, and concentrated under reduced pressure. The residue
was purified by flash chromatography (silica gel, CHCl3 then 2!4!6%
methanol/CHCl3) to give a triol (4.5 mg, 94%) as an amorphous solid:
[a]2D7 =+7.2 (c=0.067 in CHCl3); IR (film): n˜max =3437, 2937, 2875, 1645,
1-O-Methylgambierol (43): HF·pyridine (0.2 mL) was added to a solution
of methyl ether 47 (6.9 mg, 0.0068 mmol) in THF (0.6 mL) cooled to
08C. The resulting mixture was stirred at room temperature for 5 days
and then poured into cold saturated aqueous NaHCO3. The aqueous
layer was extracted several times with CHCl3. The combined organic
layers were dried over Na2SO4, filtered, and concentrated under reduced
pressure. The residue was purified by flash chromatography (silica gel,
50!70!80% ethyl acetate/hexanes) to give a diol (5.2 mg, 98%) as an
1464, 1386, 1268, 1074, 776, 677 cmꢀ1 1H NMR (500 MHz, CDCl3): d=
;
6.47 (d, J=6.9 Hz, 1H), 6.22 (dd, J=8.6, 6.9 Hz, 1H), 5.75 (dd, J=13.2,
2.9 Hz, 1H), 5.50 (dd, J=13.2, 1.7 Hz, 1H), 4.36 (d, J=8.6 Hz, 1H), 4.20
(ddd, J=9.2, 2.9 1.7 Hz, 1H), 3.64–3.59 (m, 2H), 3.48–3.40 (m, 3H), 3.34
(dd, J=11.5, 5.2 Hz, 1H), 3.19–3.10 (m, 4H), 3.07–3.03 (m, 2H), 2.22
(ddd, J=11.5, 4.6, 4.0 Hz, 1H), 2.15–2.07 (m, 2H), 2.02–1.89 (m, 4H),
1.84–1.34 (m, 15H), 1.314 (s, 3H), 1.309 (s, 3H), 1.30 (s, 3H), 1.29 (s,
3H), 1.22 ppm (s, 3H); 13C NMR (125 MHz, CDCl3): d=138.2, 131.6,
131.1, 112.7, 84.8, 83.8, 82.7, 82.2, 81.6, 79.8, 79.5, 79.3, 79.0, 76.6, 76.1,
75.8, 74.3, 73.5, 72.2, 72.0, 71.8, 62.9, 53.7, 43.8, 38.2, 37.4, 32.7, 31.8, 30.2,
29.4, 28.6, 27.6, 24.2, 21.5, 21.3, 20.4, 18.2, 15.6 ppm; HRMS (FAB): m/z
calcd for C38H5779BrO10Na [M++Na]: 775.3033; found: 775.2999; calcd
for C38H5781BrO10Na [M++Na]: 777.3021; found: 777.3036.
amorphous solid: [a]D27 =+21.6 (c=0.080 in CHCl3); IR (film): n˜max
=
3426, 2942, 2876, 1630, 1381, 1219, 1047, 773 cmꢀ1 1H NMR (500 MHz,
;
CDCl3): d=6.47 (d, J=7.4 Hz, 1H), 6.22 (dd, J=8.6, 7.4 Hz, 1H), 5.75
(dd, J=13.2, 2.9 Hz, 1H), 5.50 (dd, J=13.2, 1.7 Hz, 1H), 4.36 (d, J=
8.6 Hz, 1H), 4.20 (m, 1H), 3.76–3.72 (m, 2H), 3.69 (m, 1H), 3.48–3.40
(m, 2H), 3.38–3.34 (m, 3H), 3.32 (s, 3H), 3.29–3.10 (m, 3H), 3.08–3.03
(m, 2H), 2.23 (ddd, J=12.0, 4.6, 4.0 Hz, 1H), 2.12–2.08 (m, 2H), 2.02–
1.97 (m, 3H), 1.92–1.46 (m, 14H), 1.32 (s, 3H), 1.314 (s, 3H), 1.306 (s,
3H), 1.30 (s, 3H), 1.22 ppm (s, 3H); 13C NMR (125 MHz, CDCl3): d=
138.2, 131.7, 131.1, 112.6, 84.8, 83.9, 82.5, 81.6, 79.9, 79.4, 79.1, 76.4, 76.1,
76.0, 75.8, 75.2, 74.6, 73.8, 72.6, 72.2, 72.0, 71.8, 70.8, 58.6, 53.7, 43.6, 37.3,
35.4, 32.2, 31.8, 28.5, 27.1, 25.8, 24.2, 21.33, 21.31, 20.3, 18.2, 15.6 ppm;
HRMS (FAB): m/z calcd for C39H5979BrO11Na [M++Na]: 805.3138;
found: 805.3157; calcd for C39H5981BrO11Na [M++Na]: 807.3127; found:
807.3096.
CuCl (34.9 mg, 0.353 mmol), LiCl (23.0 mg, 0.543 mmol), and [Pd(PPh3)4]
(4.2 mg, 0.0036 mmol) were added to
a solution of the above triol
(4.4 mg, 0.0059 mmol) and (Z)-vinylstannane 23 (52.5 mg, 0.147 mmol) in
degassed DMSO/THF (1:1, v/v, 1.5 mL). The resulting mixture was stir-
red at 608C for 2 days and then quenched with 5% NH4OH. The aque-
ous layer was extracted with CHCl3. The combined organic layers were
dried over Na2SO4, filtered, and concentrated under reduced pressure.
The residue was purified by flash chromatography (silica gel, CHCl3 then
1!2!3% methanol/CHCl3) to give 35 (3.3 mg, 76%) as an amorphous
solid: [a]2D8 =+33.7 (c=0.115 in benzene); IR (film): n˜max =3433, 2941,
CuCl (30.8 mg, 0.311 mmol), LiCl (15.2 mg, 0.359 mmol), and [Pd(PPh3)4]
(2.7 mg, 0.0023 mmol) were added to
a solution of the above diol
(3.4 mg, 0.0043 mmol) and (Z)-vinylstannane 23 (62.3 mg, 0.174 mmol) in
degassed DMSO/THF (1:1, v/v, 1.7 mL). After stirring the mixture at
608C for 2 days, the reaction was quenched with 5% NH4OH. The aque-
ous layer was extracted several times with CHCl3. The combined organic
layers were dried over Na2SO4, filtered, and concentrated under reduced
pressure. The residue was purified by flash chromatography (silica gel,
50!60% ethyl acetate/hexanes) to give 43 (2.9 mg, 88%) as an amor-
phous solid: [a]2D8 =+45.0 (c=0.110 in benzene); IR (film): n˜max =3427,
2874, 1631, 1452, 1380, 1268, 1073, 755 cmꢀ1 1H NMR (500 MHz,
;
CD3CN): d=6.45 (dd, J=11.6, 10.9 Hz, 1H), 6.38 (dd, J=11.6, 11.3 Hz,
1H), 5.83 (dddd, J=17.1, 10.1, 6.3, 6.3 Hz, 1H), 5.70 (dd, J=12.9, 2.7 Hz,
1H), 5.56 (m, 1H), 5.46 (dd, J=10.9, 8.3 Hz, 1H), 5.38 (dd, J=12.9,
1.9 Hz, 1H), 5.05 (ddd, J=17.1, 3.5, 1.7 Hz, 1H), 4.98 (ddd, J=10.1, 3.5,
1.5 Hz, 1H), 4.31 (d, J=8.3 Hz, 1H), 4.21 (ddd, J=9.4, 2.7, 1.9 Hz, 1H),
3.51 (ddd, J=10.6, 8.8, 4.9 Hz, 1H), 3.47–3.39 (m, 4H), 3.34 (dd, J=11.3,
4.9 Hz, 1H), 3.21 (dd, J=11.3, 4.1 Hz, 1H), 3.18–3.12 (m, 3H), 3.05–3.00
(m, 2H), 2.96–2.93 (m, 2H), 2.67 (s, 1H), 2.55 (t, J=5.3 Hz, 1H), 2.08
(m, 1H), 1.96–1.83 (m, 4H), 1.78–1.40 (m, 17H), 1.30 (s, 3H), 1.27 (s,
3H), 1.24 (s, 3H), 1.21 (s, 3H), 1.20 ppm (s, 3H); 13C NMR (125 MHz,
CD3CN): d=140.6, 137.5, 131.5, 131.1, 129.3, 127.5, 126.0, 115.6, 85.6,
83.3, 83.1, 82.9, 82.0, 80.5, 80.2, 79.9, 79.7, 77.1, 76.8, 76.5, 75.0, 74.3, 73.1,
72.7 (2), 62.5, 54.8, 44.7, 39.2, 39.3, 33.1, 32.9, 32.3, 30.8, 29.8, 29.4, 28.6,
25.0, 21.9, 21.4, 20.8, 18.7, 15.9 ppm; HRMS (FAB): m/z calcd for
C43H64O10Na [M++Na]: 763.4397; found: 763.4404.
2943, 2873, 1631, 1385, 1268, 1072, 755 cmꢀ1 1H NMR (500 MHz,
;
CD3CN): d=6.46 (dd, J=11.5, 10.9 Hz, 1H), 6.38 (dd, J=11.5, 11.5 Hz,
1H), 5.83 (dddd, J=17.2, 10.3, 6.3, 6.3 Hz, 1H), 5.70 (dd, J=12.6, 2.3 Hz,
1H), 5.55 (m, 1H), 5.46 (m, 1H), 5.39 (dd, J=12.6, 1.7 Hz, 1H), 5.05 (dd,
J=17.2, 3.5 Hz, 1H), 4.98 (dd, J=10.3, 3.5 Hz, 1H), 4.31 (d, J=8.0 Hz,
1H), 4.21 (m, 1H), 3.74 (dd, J=12.0, 4.6 Hz, 1H), 3.67 (m, 1H), 3.59 (m,
1H), 3.51 (ddd, J=10.3, 9.2, 5.2 Hz, 1H), 3.42 (ddd, J=10.9, 9.7, 5.2 Hz,
1H), 3.36–3.30 (m, 3H), 3.29 (s, 3H), 3.23–3.13 (m, 3H), 3.07–3.00 (m,
2H), 2.96–2.93 (m, 2H), 2.82 (d, J=1.8 Hz, 1H), 2.65 (s, 1H), 2.09 (m,
1H), 1.97–1.90 (m, 3H), 1.86–1.69 (m, 4H), 1.64–1.38 (m, 12H), 1.30 (s,
3H), 1.29 (s, 3H), 1.25 (s, 3H), 1.22 (s, 3H), 1.20 ppm (s, 3H); 13C NMR
(125 MHz, CD3CN): d=140.6, 137.5, 131.5, 131.1, 129.3, 127.5, 126.0,
115.6, 85.6, 83.1, 82.9, 81.9, 80.4, 80.2, 79.7, 77.0, 76.8, 76.7, 76.5, 75.9,
75.3, 74.5, 73.1 (2), 72.7 (2), 71.2, 58.5, 54.7, 44.1, 38.2, 36.6, 33.0, 32.9,
32.2, 29.3, 27.9, 26.4, 25.0, 21.7, 21.3, 20.8, 18.7, 15.9 ppm; HRMS (FAB):
m/z calcd for C44H66O11Na [M++Na]: 793.4503; found: 793.4524.
Alcohol 46: HF·pyridine (0.15 mL) was added to a solution of tris-silyl
ether 45 (11.1 mg, 0.0090 mmol) in THF (0.9 mL) cooled to 08C. The re-
sulting mixture was stirred at 08C for 15 min and then warmed to room
temperature. The reaction mixture was stirred for 3.5 h and then poured
into cold saturated aqueous NaHCO3. The aqueous layer was extracted
several times with CHCl3. The combined organic layers were dried over
Na2SO4, filtered, and concentrated under reduced pressure. The residue
was purified by flash chromatography (silica gel, 20!40% ethyl acetate/
hexanes) to give primary alcohol 46 (7.7 mg, 86%) as a colorless oil:
[a]2D8 =+14.2 (c=0.093 in benzene); IR (film): n˜max =3436, 2929, 2857,
1-Deoxygambierol (44): HF·pyridine (0.3 mL) was added to a solution of
compound 48 (10.6 mg, 0.0108 mmol) in THF (0.9 mL) cooled to 08C.
The resulting mixture was stirred at room temperature for 5 days and
then poured into cold saturated aqueous NaHCO3. The aqueous layer
was extracted with CHCl3. The combined organic layers were dried over
Na2SO4, filtered, and concentrated under reduced pressure. The residue
was purified by flash chromatography (silica gel, 40!60% ethyl acetate/
1623, 1465, 1382, 1255, 1078, 878, 777 cmꢀ1 1H NMR (500 MHz, C6D6):
;
d=6.11 (dd, J=7.4, 6.9 Hz, 1H), 6.01 (d, J=6.9 Hz, 1H), 5.89 (dd, J=
13.2, 2.9 Hz, 1H), 5.76 (dd, J=13.2, 1.7 Hz, 1H), 4.52 (d, J=7.4 Hz, 1H),
4.34 (m, 1H), 3.99 (dd, J=12.6, 4.0 Hz, 1H), 3.85 (m, 1H), 3.65 (m, 1H),
hexanes) to give a diol (7.4 mg, 91%) as an amorphous solid: [a]D28
+35.5 (c=0.110 in CHCl3); H NMR (500 MHz, CDCl6): d=6.47 (d, J=
7.4 Hz, 1H), 6.22 (dd, J=8.0, 7.4 Hz, 1H), 5.75 (dd, J=12.6, 2.9 Hz, 1H),
=
1
Chem. Eur. J. 2004, 10, 4894 – 4909
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4907