Syntheses of (+)-Trienomycins A and F
J. Am. Chem. Soc., Vol. 118, No. 35, 1996 8327
(w), 3340 (w), 2960 (s), 2940 (s), 2860 (s), 1690 (m), 1610 (s) cm-1
(25% ethyl acetate/hexanes) afforded 43 (39.2 mg, 62% yield) as a
colorless oil: IR (CHCl3) 1725 (s), 1590 (s), 1455 (s) cm-1; 1H NMR
(500 MHz, C6D6) δ 9.54 (dd, J ) 2.9, 1.4 Hz, 1 H), 7.39-7.38 (m, 1
H), 7.29-7.28 (m, 1 H), 6.71 (s, 1 H), 6.70-6.67 (m, 1 H), 5.20-
5.14 (m, 1 H), 4.77 (d, J ) 5.8 Hz, 1 H), 3.76-3.72 (m, 1 H), 3.31 (d,
J ) 5.7 Hz, 1 H), 3.05 (s, 3 H), 2.52-2.07 (m, 8 H), 1.79 (br s, 3 H),
1.60 (s, 3 H), 1.32 (s, 3 H), 1.27 (s, 3 H), 1.00 (s, 9 H), 0.63 (d, J )
6.9 Hz, 3 H), 0.21 (s, 3 H), 0.20 (s, 3 H); 13C NMR (125 MHz, C6D6)
δ 199.7, 172.4, 169.4, 156.6, 144.5, 139.1, 134.7, 125.7, 118.2, 114.7,
111.4, 101.1, 88.0, 77.5, 70.2, 69.6, 56.7, 47.7, 41.0, 37.1, 36.4, 29.9,
25.8, 24.3, 24.1, 21.1, 20.4, 18.4, 12.3, -4.4; high-resolution mass
spectrum (CI, NH3) m/z 635.3744 [(M + NH4)+; calcd for C33H55N2O8-
Si: 635.3727].
;
1H NMR (500 MHz, CDCl3) δ 7.78 (br s, 1 H), 7.66-7.61 (m, 4 H),
7.46-7.24 (complex m, 11 H), 7.03, 6.99 (diastereomers, br s, br s, 1
H), 6.74, 6.71 (diastereomers, br s, br s, 1 H), 6.30, 6.21 (diastereomers,
br s, br s, 1 H), 4.72, 4.69 (diastereomers, t, J ) 6.8 Hz, t, J ) 7.1 Hz,
1 H), 4.52, 4.50 (diastereomers, d, J ) 5.5 Hz, d, J ) 5.6 Hz, 1 H),
3.76, 3.73 (diastereomers, dd, J ) 11.1, 4.0 Hz, dd, J ) 12.5, 3.9 Hz,
1 H), 3.71-3.56 (complex series of m, 6 H), 3.46, 3.42 (diastereomers,
ddd, J ) 9.1, 9.1, 2.7 Hz, ddd, J ) 9.5, 9.5, 2.8 Hz, 1 H), 3.37, 3.35
(diastereomers, s, s, 3 H), 3.21, 3.07 (diastereomers, m, m, 1 H), 2.53-
2.45 (m, 1 H), 2.38 (dd, J ) 15.0, 7.7 Hz, 1 H), 1.75-1.59 (complex
series of m, 3 H), 1.50, 1.47 (diastereomers, s, s, 3 H), 1.33, 1.28
(diastereomers, s, s, 3 H), 1.28, 1.27 (diastereomers, s, s, 3 H), 1.06,
1.05 (diastereomers, s, s, 9 H), 0.89 (s, 9 H), 0.87 (s, 9 H), 0.71, 0.63
(diastereomers, d, J ) 6.9 Hz, d, J ) 6.9 Hz, 3 H), 0.05, 0.04
(diastereomers, s, s, 6 H), 0.03 (s, 6 H); 13C NMR (125 MHz, CDCl3)
δ 168.9, 155.9, 138.9, 138.8, 137.6, 137.4, 136.8, 135.5, 133.8, 133.1,
132.7, 132.6, 129.9, 128.9, 128.5, 128.4, 127.7, 120.2, 120.1, 116.6,
114.4, 114.1, 111.5, 100.5, 78.8, 71.4, 71.2, 71.0, 70.9, 70.5, 70.1, 63.9,
59.4, 57.7, 40.5, 40.4, 39.9, 37.8, 37.7, 26.5, 26.1, 25.9, 25.8, 24.6,
23.9, 21.2, 21.1, 19.4, 18.2, 18.1, 12.1, 12.0, -5.3, -5.4, -5.5; high-
resolution mass spectrum (FAB, NBA) m/z 1014.4825 [(M - t-Bu)+;
calcd for C55H80NO9SSi3: 1014.4862]. Anal. Calcd for C59H89NO9-
SSi3: C, 65.98; H, 8.29; N, 1.30. Found: C, 65.97; H, 8.16; N, 1.25.
Aminal 44. A solution of acetate 43 (30.0 mg, 0.05 mmol) in
anhydrous MeOH (1 mL) was cooled to -20 °C, treated with anhydrous
K2CO3 (7.0 mg, 0.05 mmol) stirred for 1 h, and then poured into ethyl
acetate (10 mL). The resultant solution was washed with saturated
aqueous NH4Cl (5 mL), dried over MgSO4, filtered, and concentrated
in vacuo. Flash chromatography (50% ethyl acetate/hexanes) provided
44 (22.6 mg, 81% yield) as a 4:1 diastereomer mixture: colorless oil;
IR (CHCl3) 3610-3310 (br, w), 2930 (s), 1710 (s), 1590 (s), 1480 (s),
1400 (s) cm-1; 1H NMR (500 MHz, C6D6) δ 9.47 (dd, J ) 3.0, 1.5 Hz,
1 H), 7.57-7.55 (m, 1 H), 7.34-7.32 (m, 1 H), 6.80-6.78 (m, 1 H),
5.35 (d, J ) 5.9 Hz, 1 H), 5.23-5.17 (m, 1 H), 4.77 (d, J ) 5.8 Hz,
1 H), 3.67 (ddd, J ) 8.6, 8.6, 3.5 Hz, 1 H), 3.31 (d, J ) 5.6 Hz, 1 H),
2.87 (s, 3 H), 2.60-2.30 (complex series of m, 8 H), 1.81 (br s, 3 H),
1.62-1.55 (m, 1 H), 1.30 (s, 3 H), 1.25 (s, 3 H), 1.01 (s, 9 H), 0.63 (d,
J ) 6.9 Hz, 3 H), 0.25 (s, 3 H), 0.24 (s, 3 H); 13C NMR (125 MHz,
C6D6) δ 200.6, 200.1, 171.5, 169.8, 156.5, 156.4, 144.2, 144.0, 139.9,
139.7, 134.8, 134.7, 125.8, 117.8, 117.6, 115.0, 114.9, 111.9, 111.7,
101.1, 88.5, 83.1, 80.1, 73.5, 70.4, 70.3, 69.6, 69.5, 56.7, 56.2, 47.7,
41.0, 40.9, 36.6, 36.5, 36.0, 30.3, 30.2, 25.9, 24.5, 24.4, 24.1, 21.1,
21.0, 18.4, 12.3, -4.3; high-resolution mass spectrum (FAB, NBA)
m/z 500.2495 [(M - t-Bu - H2O)+; calcd for C27H38NO6Si: 500.2468].
TBS Ether (+)-46. A solution of alcohol (-)-35 (329 mg, 0.53
mmol) in CH2Cl2 (5.3 mL) was treated with imidazole (94 mg, 1.38
mmol) and chloro-tert-butyldimethylsilane (105 mg, 0.69 mmol). The
resultant heterogeneous mixture was stirred at room temperature for
20 min, diluted with ether (50 mL), and washed with water and brine
(10 mL each). The combined aqueous phases were extracted with ether
(50 mL), and the combined organic solutions were dried over MgSO4,
filtered, and concentrated in vacuo. Flash chromatography (25% ethyl
acetate/hexanes) gave (+)-46 (364 mg, 94% yield) as a colorless oil:
[R]2D3 +1.2° (c 0.95, CHCl3); IR (CHCl3) 3430 (w), 3330 (w), 1713
(s), 1690 (s), 1605 (s), 1465 (s), 1430 (s), 1320 (s), 1310 (s) cm-1; 1H
NMR (500 MHz, CDCl3) δ 7.84 (br s, 1 H), 7.63 (dd, J ) 8.0, 1.3 Hz,
4 H), 7.54 (dd, J ) 8.2, 0.9 Hz, 2 H), 7.49 (apparent t, J ) 7.4 Hz, 1
H), 7.42-7.38 (m, 2 H), 7.36-7.32 (m, 6 H), 6.89 (br s, 1 H), 6.82 (br
s, 1 H), 6.22 (br s, 1 H), 4.05 (s, 2 H), 3.65-3.61 (m, 2 H), 3.59-3.56
(m, 1 H), 3.35 (s, 3 H), 2.46 (dd, J ) 14.9, 3.4 Hz, 1 H), 2.38 (dd, J
) 14.9, 7.7 Hz, 1 H), 1.05 (s, 9 H), 0.87 (s, 9 H), 0.03 (s, 6 H); 13C
NMR (125 MHz, CDCl3) δ 169.0, 155.9, 139.0, 137.9, 135.5, 133.4,
132.5, 129.9, 129.6, 128.7, 128.5, 127.8, 117.7, 115.0, 111.5, 78.8,
63.9, 62.6, 57.7, 39.8, 26.5, 25.8, 19.4, 18.2, -5.5; high-resolution mass
spectrum (FAB, NBA) m/z 754.3035 [(M + Na)+; calcd for
C40H53NO6SSi2Na: 754.3030]. Anal. Calcd for C40H53NO6SSi2: C,
65.66; H, 7.25; N, 1.92. Found: C, 65.58; H, 7.36; N, 1.73.
Desulfonylated Arene (+)-48. A mixture of sulfone 47 (55 mg,
0.051 mmol), Na2HPO4 (29 mg, 0.21 mmol), and anhydrous methanol
(1 mL) was cooled to -20 °C and stirred for 20 min. Excess 5%
Na(Hg) (∼250 mg) was then added. The reaction mixture was stirred
vigorously at -20 °C for 15 min, diluted with ethyl acetate (10 mL),
and filtered through a plug of silica gel with ethyl acetate as eluant.
After concentration in vacuo, the residue was dissolved in ethyl acetate
(10 mL) and the solution was washed with water and brine (5 mL each),
dried over anhydrous MgSO4, filtered, and concentrated in vacuo. Flash
chromatography (15% ethyl acetate/hexanes) afforded (+)-48 (45 mg,
94% yield) as a colorless oil: [R]2D3 +2° (c 0.6, CHCl3); IR (CHCl3)
3440 (w), 3340 (w), 2960 (s), 2860 (s), 1730 (m), 1685 (m), 1465 (s),
1
1430 (s), 1255 (s) cm-1; H NMR (500 MHz, CDCl3) δ 7.84 (br s, 1
H), 7.71 (apparent d, J ) 6.8 Hz, 4 H), 7.42-7.33 (complex series of
m, 6 H), 6.99 (br s, 1 H), 6.76 (br s, 1 H), 6.28 (br s, 1 H), 5.10 (t, J
) 6.6 Hz, 1 H), 4.64 (d, J ) 5.7 Hz, 1 H), 3.69-3.62 (complex series
of m, 5 H), 3.47 (apparent dt, J ) 9.0, 9.0 Hz, 1 H), 3.40 (s, 3 H), 2.52
(dd, J ) 14.9, 3.3, 1 H), 2.44 (dd, J ) 15.0, 7.8, 1 H), 2.39 (t, J ) 7.8
Hz, 2 H), 2.09 (m, 2 H), 1.80-1.60 (complex series of m, 3 H), 1.64
(s, 3 H), 1.31 (s, 3 H), 1.30 (s, 3 H), 1.10 (s, 9 H), 0.90 (s, 9 H), 0.89
(s, 9 H), 0.75 (d, J ) 6.9 Hz, 3 H), 0.06 (s, 6 H), 0.05 (s, 3 H); 13C
NMR (125 MHz, CDCl3) δ 168.9, 155.8, 143.8, 138.7, 135.5, 134.5,
132.9, 129.8, 127.7, 125.0, 115.6, 112.7, 108.7, 100.4, 78.9, 70.9, 69.3,
64.0, 59.5, 57.8, 41.0, 39.9, 37.7, 36.0, 29.2, 26.5, 25.9, 25.8, 24.6,
24.1, 20.8, 19.4, 18.2, 18.1, 12.2, -5.3, -5.4; high-resolution mass
spectrum (FAB, NBA) m/z 954.5496 [(M + Na)+; calcd for
C53H85NO7Si3Na: 954.5532]. Anal. Calcd for C53H85NO7Si3: C,
68.31; H, 9.13; N, 1.50. Found: C, 68.41; H, 9.03; N, 1.39.
N-Protected Amide (+)-49. At 0 °C a solution of amide (+)-48
(76 mg, 0.082 mmol) in anhydrous THF (1.6 mL) was treated with
KH (65 mg, 1.63 mmol, washed with THF). After 5 min chloromethyl
2,2,2-trichloroethyl ether (16 µL, 0.12 mmol) was added, and the
reaction mixture was then warmed to ambient temperature, stirred for
20 min, cooled to 0 °C, and slowly quenched with saturated aqueous
NaHCO3 (5 mL). The biphasic mixture was extracted with ether (20
mL), and the organic phase was washed with brine (5 mL), dried over
MgSO4, filtered, and concentrated in vacuo. Flash chromatography
(15% ethyl acetate/hexanes) furnished (+)-49 (83.2 mg, 93% yield) as
a colorless oil: [R]2D3 +4.0° (c 1.03, CHCl3); IR (CHCl3) 2920 (s),
2850 (s), 1720 (w), 1655 (m), 1585 (s), 1450 (s) cm-1; 1H NMR (500
MHz, CDCl3) δ 7.68-7.66 (m, 4 H), 7.41-7.33 (complex series of m,
6 H), 6.60 (m, 1 H), 6.58 (m, 1 H), 6.39 (m, 1 H), 5.16-5.08 (complex
series of m, 3 H), 4.63 (d, J ) 5.7 Hz, 1 H), 4.14 (m, 2 H), 3.68-3.65
(complex series of m, 3 H), 3.54 (m, 1 H), 3.49-3.47 (m, 2 H), 3.32
(s, 3 H), 2.44 (t, J ) 7.8 Hz, 2 H), 2.19-2.10 (complex series of m,
4 H), 1.77-1.58 (complex series of m, 3 H), 1.64 (s, 3 H), 1.30 (s, 6
H), 1.09 (s, 9 H), 0.89 (s, 9 H), 0.84 (s, 9 H), 0.76 (d, J ) 6.9 Hz, 3
H), 0.04 (s, 3 H), 0.01 (s, 3 H), 0.00 (s, 3 H); 13C NMR (125 MHz,
Coupling Product 47. A solution of sulfone (+)-46 (700 mg, 0.96
mmol) in anhydrous THF (10 mL) was cooled to -78 °C, and sodium
bis(trimethylsilyl)amide (0.8 M in THF, 2.6 mL) was added dropwise.
The resultant deep yellow solution was stirred at -78 °C for 10 min,
and then freshly prepared iodide (-)-38 (310 mg, 0.66 mmol) in THF
(2.5 mL plus 2-mL rinse) was introduced via a cannula. After 10 min
at -78 °C, the reaction mixture was transferred by cannula into a cold
(0 °C), vigorously stirred mixture of pH 7 buffer and ether (1:1, 100
mL). The mixture was warmed to room temperature, the layers were
separated, and the aqueous phase was extracted with ether (2 × 50
mL). The combined organic solutions were dried over MgSO4, filtered,
and concentrated in vacuo. Flash chromatography (20% ethyl acetate/
hexanes) provided 47 (645 mg, 91% yield) as a white foam. Further
elution (30% ethyl acetate/hexanes) gave recovered (+)-46 (123 mg).
NMR analysis revealed a 1.5:1 diastereomer ratio: IR (CHCl3) 3440