Pyranosylated Indolocarbazoles
J. Am. Chem. Soc., Vol. 119, No. 41, 1997 9659
148.7, 140.1, 136.8, 130.8, 129.4, 127.0, 126.4, 125.3, 124.8, 124.3,
123.7, 120.7, 120.4, 120.2, 120.0, 119.6, 116.0, 115.5, 114.5, 111.6,
111.5, 107.1, 90.7, 83.2, 79.5, 60.6, 57.4, 56.1, 56.0, 49.9, 46.5, 33.6,
30.1; high-resolution mass spectrum (FAB) m/z 604.2449 [calcd for
C36H34N3O6 (M + H) 604.2448].
3H), 3.72 (s, 3H), 3.62 (s, 3H), 3.55 (ddd, J ) 2.3, 6.1, 10.1 Hz, 1H),
2.37 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ 168.8, 148.9, 148.1,
140.3, 136.5, 130.4, 129.9, 127.8, 125.7, 125.0, 124.7, 123.5, 122.7,
120.8, 120.2, 119.9, 119.9, 118.7, 115.5, 114.8, 114.1, 112.0, 111.7,
108.8, 95.6, 87.3, 83.1, 71.7, 65.6, 61.6, 55.5, 55.5, 49.6, 45.5, 29.0;
high-resolution mass spectrum (FAB) m/z 620.2390 [calcd for C36H34N3O7
(M + H) 620.2397].
(+)-RK286c (3). To a stirred solution of ether (+)-52 (10 mg, 0.017
mmol, 1.0 equiv) in anisole or thioanisole (80 µL) was added TFA
(0.5 mL). After the reaction had proceeded to completion as evidenced
by TLC (ca. 24 h), H2O (1.0 mL) was added and the derived mixture
extracted with CH2Cl2 (3 × 5mL). The combined organic layers were
washed with saturated aqueous NaHCO3 (5 mL), dried over Na2SO4,
and evaporated to a residue which was purified by preparative TLC
(5% MeOH/CH2Cl2) to provide (+)-RK-286c (3, 6 mg, 75% yield) as
a pale white powder: mp >255 °C (dec); [R]20D +41 (c 0.18, EtOAc);
IR (thin film/NaCl) 3354.0 (br m), 2920.4 (s), 2851.6 (m), 1677.2 (s),
1636.0 (m), 1585.3 (m), 1456.2 (s), 1352.8 (s), 1318.7 (s), 1231.7 (m),
(+)-MLR-52 (5). To a stirred solution of diol (+)-54 (10 mg, 0.016
mmol, 1.0 equiv) in anisole or thioanisole (80 µL) was added TFA
(0.5 mL). The reaction was monitored by TLC and after 16 h had
proceeded to completion. The reaction mixture was treated with H2O
(1.0 mL) and then extracted with CH2Cl2 (3 × 5 mL). The combined
organic layers were washed with saturated aqueous NaHCO3 (5 mL),
dried over Na2SO4, and evaporated to a residue. Purification by
preparative TLC (5% MeOH/CH2Cl2) provided (+)-MLR-52 (5, 6 mg,
77% yield) as a white solid: mp >260 °C (dec); [R]20 +65 (c 0.1,
D
1
1117.3 (m), 743.8 (s) cm-1; H NMR (500 MHz, DMSO-d6) δ 9.27
MeOH); IR (thin film/NaCl) 3348.5 (br m), 2922.9 (s), 2851.9 (m),
1638.2 (s), 1586.6 (m), 1455.5 (s), 1373.5 (m), 1336.6 (m), 1320.8
(d, J ) 7.9 Hz, 1H), 8.47 (br s, 1H), 7.99 (d, J ) 8.5 Hz, 1H), 7.94 (d,
J ) 7.7 Hz, 1H), 7.59 (d, J ) 8.2 Hz, 1H), 7.45 (app t, J ) 7.4 Hz,
1H), 7.40 (app t, J ) 7.5 Hz, 1H), 7.26 (app t, J ) 7.5 Hz, 2H), 6.78
(d, J ) 5.3 Hz, 1H), 4.95 (d, J ) 17.6 Hz, 1H), 4.89 (d, J ) 17.7 Hz,
1H), 4.25 (br s, 1H), 4.17 (br s, 1H), 3.83 (d, J ) 2.7 Hz, 1H), 3.41 (s,
3H), 2.60 (ddd, J ) 3.2, 5.6, 14.8 Hz, 1H), 2.41 (dd, J ) 3.3, 14.8 Hz,
1H), 2.31 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ 139.7, 136.1,
129.5, 125.5, 124.7, 124.1, 123.9, 122.6, 120.6, 119.5, 118.9, 118.6,
115.7, 108.6, 90.9, 82.3, 79.5, 58.8, 56.4, 45.3, 33.9, 29.9; high-
resolution mass spectrum (FAB) m/z 454.1766 [calcd for C27H24N3O4
(M + H) 454.1767].
(m), 1275.0 (m), 1224.7 (m), 1200.3 (w), 1119.5 (s), 740.8 (s) cm-1
;
1H NMR (500 MHz, DMSO-d6) δ 9.31 (d, J ) 7.9 Hz, 1H), 8.61 (br
s, 1H), 7.99 (d, J ) 7.7 Hz, 1H), 7.96 (d, J ) 8.7 Hz, 1H), 7.62 (d, J
) 8.2 Hz, 1H), 7.53 (app t, J ) 7.5 Hz, 1H), 7.45 (td, J ) 0.8, 7.7 Hz,
1H), 7.32 (app t, J ) 7.4 Hz, 1H), 7.32 (app t, J ) 7.4 Hz, 1H), 6.58
(d, J ) 1.6 Hz, 1H), 6.12 (d, J ) 4.0 Hz, 1H), 5.06 (d, J ) 5.9 Hz,
1H), 4.99 (d, J ) 17.6 Hz, 1H), 4.95 (d, J ) 17.5 Hz, 1H), 4.13 (d, J
) 10.3 Hz, 1H), 4.12 (dd, J ) 1.6, 2.6 Hz, 1H), 3.62 (s, 3H), 3.56
(ddd, J ) 2.6, 6.2, 10.3 Hz, 1H), 3.28 (s, 3H), 2.38 (s, 3H); 13C NMR
(125 MHz, DMSO-d6) δ 171.8, 140.2, 136.4, 132.6, 127.8, 125.8, 125.5,
124.8, 124.6, 123.6, 122.7, 120.9, 120.1, 119.7, 119.3, 115.4, 114.9,
114.3, 108.7, 95.6, 87.2, 83.1, 71.7, 65.6, 61.6, 45.4, 29.0; high-
resolution mass spectrum (FAB) m/z 470.1717 [calcd for C27H24N3O5
(M + H) 470.1716].
Olefin (+)-53. To a stirred solution of ether (+)-52 (112 mg, 0.186
mmol, 1.0 equiv) in CDCl3 (2.0 mL) was added Martin’s sulfurane
(187 mg, 0.28 mmol, 1.5 equiv). The reaction rapidly proceeded to a
less polar product as evidenced by TLC and after 20 min was complete.
Solvent was evaporated and the residue subjected to flash chromatog-
raphy (2:1 hexanes/EtOAc eluent) to provide olefin (+)-53 (96 mg,
Oxime (-)-55. A suspension of ketone (+)-12 (100 mg, 0.17 mmol,
1.0 equiv), hydroxylamine hydrochloride (165 mg, 2.38 mmol, 14.0
equiv), and NaOAc (167 mg, 2.04 mmol, 12 equiv) in 80% aqueous
EtOH (35.0 mL) was heated gently to reflux for 30 min. Following
cooling to room temperature, the sovent was removed in Vacuo and
the residue purified by flash chromatography (1:1 hexanes/EtOAc
eluent) to provide oxime (-)-55 (98 mg, 95% yield) as a yellow
powder: mp >270 °C (dec); [R]20D -18 (c 0.1, CH2Cl2); IR (thin film/
NaCl) 3324.0 (br m), 2995.0 (w), 2911.3 (m), 1660.0 (s), 1589.7 (m),
1513.5 (s), 1461.1 (s), 1417.9 (m), 1399.0 (m), 1349.2 (s), 1315.5 (m),
88% yield) as a white solid: mp 185-187 °C; [R]20 +36 (c 0.1,
D
MeOH); IR (thin film/NaCl) 2920.5 (s), 2851.5 (s), 1709.8 (m), 1674.3
(s), 1589.0 (m), 1513.7 (m), 1457.5 (s), 1222.9 (m), 1026.6 (m), 745.3
1
(m) cm-1; H NMR (500 MHz, DMSO-d6, 315 K) δ 9.31 (d, J ) 7.9
Hz, 1H), 8.11 (d, J ) 8.6 Hz, 1H), 7.91 (d, J ) 7.7 Hz, 1H), 7.86 (d,
J ) 8.2 Hz, 1H), 7.50 (td, J ) 1.0, 7.34 Hz, 1H), 7.43 (app t, J ) 7.8
Hz, 1H), 7.31 (app t, J ) 7.0 Hz, 1H), 7.28 (app t, J ) 7.1 Hz, 1H),
7.13 (d, J ) 1.9 Hz, 1H), 7.02 (s, 1H), 6.93 (d, J ) 8.6 Hz, 1H), 6.92
(d, J ) 8.6 Hz, 1H), 6.09 (d, J ) 10.4 Hz, 1H), 5.77 (dt, J ) 2.3, 10.4
Hz, 1H), 4.95 (s, 2H), 4.85 (d, J ) 15.1 Hz, 1H), 4.81 (d, J ) 15.1
Hz, 1H), 4.48 (d, J ) 1.4 Hz, 1H), 3.74 (s, 3H), 3.71 (s, 3H), 3.57 (s,
3H), 2.20 (s, 3H); 13C NMR (125 MHz, acetone-d6) δ 169.9, 150.5,
149.7, 141.3, 137.4, 131.8, 131.2, 130.5, 127.7, 127.1, 126.4, 126.2,
125.5, 125.3, 124.3, 121.5, 121.2, 121.1, 120.5, 120.4, 118.0, 117.1,
115.9, 112.8, 112.8, 109.1, 91.5, 80.8, 78.8, 57.7, 56.0, 56.0, 50.5, 46.5,
28.0; high-resolution mass spectrum (FAB) m/z 586.2343 [calcd for
C36H32N3O5 (M + H) 586.2342].
Diol (+)-54. To a stirred solution of 4-methylmorpholine-N-oxide
(6 mg, 0.05 mmol, 1.2 equiv) and OsO4 (0.6 mL of a 2.5% solution in
t-BuOH, 0.05 mmol, 1.2 equiv) in 4:1 acetone:H2O (2 mL) was added
a solution of olefin (+)-53 (25 mg, 0.043 mmol, 1.0 equiv) in acetone
(1 mL). The reaction was monitored by TLC and after 16 h had
proceeded to completion. At this time, NaHSO3 (100 mg) in H2O (1.0
mL) was added, and the resulting black solution was stirred for 20
min, filtered, and extracted with CH2Cl2 (3 × 15 mL). The combined
organic layers were dried over Na2SO4, evaporated to a residue, and
purified by flash chromatography (1:1 hexanes/EtOAc eluent) to provide
diol (+)-54 (23 mg, 84% yield) as a white powder: mp 227-230 °C;
[R]20D +17 (c 0.1, MeOH); IR (thin film/NaCl) 3411.2 (br m), 2929.3
(m), 2849.4 (w), 2656.3 (m), 1590.0 (m), 1514.0 (m), 1461.2 (s), 1350.9
(m), 1273.6 (s), 1127.1 (s), 1025.0 (m), 743.3 (s) cm-1; 1H NMR (500
MHz, DMSO-d6) δ 9.36 (d, J ) 7.9 Hz, 1H), 7.95 (d, J ) 8.6 Hz,
1H), 7.94 (d, J ) 7.6 Hz, 1H), 7.64 (d, J ) 8.1 Hz, 1H), 7.55 (app t,
J ) 7.6 Hz, 1H), 7.45 (app t, J ) 7.7 Hz, 1H), 7.35 (app t, J ) 7.5 Hz,
1H), 7.29 (app t, J ) 7.5 Hz, 1H), 7.02 (s, 1H), 6.94 (s, 2H), 6.59 (d,
J ) 1.6 Hz, 1H), 6.13 (d, J ) 3.8 Hz, 1H), 5.07 (d, J ) 6.0 Hz, 1H),
4.99 (d, J ) 17.8 Hz, 1H), 4.95 (d, J ) 17.8 Hz, 1H), 4.83 (s, 2H),
4.12 (d, J ) 10.1 Hz, 1H), 4.12 (dd, J ) 2.3, 3.8 Hz, 1H), 3.74 (s,
1
1260.0 (s), 1234.6 (m), 1124.4 (m), 1027.2 (m), 741.7 (s) cm-1; H
NMR (500 MHz, DMSO-d6) δ 10.30 (s, 1H), 9.34 (d, J ) 7.9 Hz,
1H), 8.08 (d, J ) 8.6 Hz, 1H), 7.90 (d, J ) 7.6 Hz, 1H), 7.71 (d, J )
8.3 Hz, 1H), 7.51 (app t, J ) 7.6 Hz, 1H), 7.42 (app t, J ) 7.9 Hz,
1H), 7.32 (app t, J ) 7.7 Hz, 1H), 7.28 (app t, J ) 7.4 Hz, 1H), 7.04
(d, J ) 6.3 Hz, 1H), 7.03 (s, 1H), 6.95 (d, J ) 8.4 Hz, 1H), 6.93 (d,
J ) 8.2 Hz, 1H), 5.56 (m, 2H), 4.97 (d, J ) 18.1 Hz, 1H), 4.93 (d, J
) 16.9 Hz, 1H), 4.85 (d, J ) 15.0 Hz, 1H), 4.45 (d, J ) 15.0 Hz, 1H),
3.75 (s, 3H), 3.72 (s, 3H), 3.61 (d, J ) 13.9 Hz, 1H), 3.01 (dd, J )
5.8, 14.3 Hz, 1H), 2.46 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ
168.8, 148.9, 148.1, 147.4, 140.2, 136.1, 130.5, 129.6, 128.1, 125.4,
125.3, 124.7, 124.6, 123.6, 122.8, 120.5, 120.1, 119.9, 119.6, 118.5,
116.0, 114.8, 113.9, 112.1, 111.9, 108.9, 97.4, 82.0, 74.9, 55.5, 55.5,
49.5, 45.5, 29.6, 28.6; high-resolution mass spectrum (FAB) m/z
603.2238 [calcd for C35H31N4O6 (M + H) 603.2244].
Methyl Ether (-)-56. To a mixture of oxime (-)-55 (90 mg, 0.15
mmol, 1.0 equiv), MeI (88 µL, 1.42 mmol, 9.5 equiv), and powdered
KOH (88 mg, 1.58 mmol, 10.5 equiv) in THF (15 mL) was added
n-Bu4NBr (10 mg, 0.03 mmol, 0.2 equiv). The mixture was stirred
under N2 for 30 min, solvent was removed in Vacuo, and the residue
was subjected to flash chromatography (1:1 hexanes/EtOAc eluent) to
provide methyl ether (-)-56 (85 mg, 90% yield) as a yellow powder:
mp >270 °C (dec); [R]20 -22 (c 0.1, CH2Cl2); IR (thin film/NaCl)
D
2998.0 (w), 2926.3 (m), 1674.1 (s), 1590.0 (m), 1513.7 (s), 1460.9 (s),
1418.2 (m), 1397.9 (s), 1349.4 (s), 1316.2 (s), 1262.1 (m), 1225.6 (m),
1
1044.3 (m), 743.5 (m) cm-1; H NMR (500 MHz, DMSO-d6, 345 K)
δ 9.36 (d, J ) 8.0 Hz, 1H), 7.99 (d, J ) 8.6 Hz, 1H), 7.93 (d, J ) 7.8
Hz, 1H), 7.68 (d, J ) 8.3 Hz, 1H), 7.51 (app t, J ) 7.6 Hz, 1H), 7.44
(app t, J ) 7.8 Hz, 1H), 7.33 (app t, J ) 7.2 Hz, 1H), 7.30 (app t, J
) 7.1 Hz, 1H), 7.04 (s, 1H), 7.02 (d, J ) 5.6 Hz, 1H), 6.97 (d, J ) 9.4