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N. Saito et al. / Tetrahedron 60 (2004) 3873–3881
hydride (1.0 M, 0.2 ml, 0.2 mmol) was added dropwise over
10 min at 220 8C, and stirring was continued at 220 8C for
4 h. After quenching by the addition of water (0.1 ml) and
chloroform (10 ml), stirring was continued at room
temperature overnight. The reaction mixture was diluted
with brine (30 ml) and extracted with chloroform
(30 ml£3). The combined extracts were washed with brine
(30 ml), dried, and concentrated in vacuo to give a residue
(19.2 mg) that was subjected to chromatography on a silica
gel (1.5 g) column with hexane–ethyl acetate (3:1) as the
eluent to give the alcohol (3: 4.7 mg, 34.3%) and 1m
(3.4 mg, 21.3% recovery).
(s, C-16), 61.5 (t, C-22), 61.0 (q, OCH3), 60.9 (q, OCH3),
58.7 (t, C-21), 58.7 (d, C-1), 57.2 (d, C-13), 54.8 (d, C-3),
52.2 (d, C-11), 41.1 (q, NCH3), 26.2 (t, C-4), 22.7 (t, C-14),
8.7 (q, 6-CH3), 8.7 (q, 16-CH3); FAB-MS (m-nitrobenzyl
alcohol) m/z (%) 469 (Mþþ1, 6), 437 (3), 391 (3), 307 (17),
289 (12), 220 (30), 218 (20), 154 (100), 136 (72); HR-
FABMS m/z 469.1970 [Mþþ1] (calcd for C25H29N2O7,
469.1975).
1.1.3. 9-[Acetoxymethyl]-7-cyano-6,7,9,14,14a,15-hexa-
hydro-2,11-dimethoxy-3,12,16-tri-methyl-(6S,7S,9R,
14aS,15R)-(2)-6,15-imino-4H-isoquino[3,2-b][3]benza-
zocine-1, 4,10,13(9H)-tetrone (6). Acetyl chloride (9.4 ml,
0.13 mmol) was added to a solution of 3 (16.4 mg,
0.033 mmol), triethylamine (9.2 ml, 0.0066 mmol), and
4-dimethylaminopyridine (8.1 mg, 0.0066 mmol) in
dichloromethane (4 ml) at 0 8C, and the reaction mixture
was stirred at 25 8C for 1 h. The reaction mixture was
diluted with water (20 ml) and extracted with dichloro-
methane (20 ml£3). The combined extracts were washed
with brine (20 ml), dried, and concentrated in vacuo to give
a residue (18.7 mg), the purification of which by flash silica
gel column chromatography (hexane–ethyl acetate 5:1)
afforded the acetate (6, 12.9 mg, 72.9%) as an amorphous
powder. [a]2D5¼294.5 (c 0.2, CHCl3); CD D 1 nm, (c
94.3 mM, methanol, 24 8C) 23.5 (351), 21.5 (300), 27.0
(280), þ4.5 (256), 21.3 (230), 20.6 (222); IR (CHCl3)
3026, 2964, 2854, 1741, 1656, 1615, 1449, 1375, 1310,
1233, 1162 cm21; UV lmax (log 1) 269 (4.59), 370 (3.13)
nm; 1H NMR (CDCl3, 500 MHz) d 4.44 (1H, d, J¼2.4 Hz,
21-H), 4.43 (1H, dd, J¼11.3, 3.4 Hz, 22-H), 4.36 (1H, ddd,
J¼3.7, 3.1, 2.4 Hz, 1-H), 4.01 (3H, s 17-OCH3), 3.99 (3H, s,
7-OCH3), 3.91 (1H, d, J¼2.7 Hz, 11-H), 3.82 (1H, dd,
J¼11.3, 3.6 Hz, 22-H), 3.18 (1H, dd, J¼7.9, 2.4 Hz, 13-H),
3.16 (1H, ddd, J¼11.2, 2.7, 2.1 Hz, 3-H), 2.84 (1H, dd,
J¼16.8, 2.1 Hz, 4-Ha), 2.66 (1H, dd, J¼21.1, 7.9 Hz,
14-Ha), 2.27 (3H, s, NCH3), 2.25 (1H, d, J¼21.1 Hz,
14-Hb), 1.96 (3H, s, 16-CH3), 1.94 (3H, s, 6-CH3), 1.76
(3H, s, COCH3), 1.29 (1H, ddd, J¼16.8, 11.2, 2.7 Hz,
4-Hb); 13C NMR (CDCl3, 125 MHz) d 186.1 (s, C-15),
185.4 (s, C-5), 182.5 (s, C-18), 181.0 (s, C-8), 169.9 (s, CO),
155.5 (s, C-7), 155.2 (s, C-17), 142.2 (s, C-20), 141.8 (s,
C-10), 135.4 (s, C-9), 134.9 (s, C-19), 128.7 (s, C-6), 128.7
(s, C-16), 116.9 (s, CN), 63.6 (t, C-22), 61.1 (q, OCH3), 61.0
(q, OCH3), 59.7 (d, C-21), 55.8 (d, C-1), 54.6 (d, C-13), 54.5
(d, C-3), 54.3 (d, C-11), 41.5 (q, NCH3), 25.3 (t, C-4), 21.3
(t, C-14), 20.5 (q, COCH3), 8.8 (q, 6-CH3), 8.6 (q, 16-CH3);
EIMS m/z (%) 535 (Mþ, 7), 260 (8), 243 (6), 221 (19), 220
(100), 218 (24), 204 (12); HR-EIMS m/z 535.1953 [Mþ]
(calcd for C28H29N3O8, 535.1955).
Compound 3. [a]2D5¼2270.6 (c 1.0, CHCl3); CD D 1 nm (c
103.3 mM, methanol, 24 8C) 22.9 (352), 21.5 (300), 210.2
(280), þ3.2 (257), 21.8 (230); IR (CHCl3) 3631, 3368,
3015, 2945, 2840, 1656, 1449, 1375, 1311, 1189 cm21; UV
1
lmax (log 1) 269 (4.61), 370 (3.11) nm; H NMR (CDCl3,
500 MHz) d 4.15 (1H, d, J¼2.4 Hz, 21-H), 4.07 (1H, d,
J¼2.6 Hz, 11-H), 4.03, 3.98 (each, 3H, s, 7-OCH3 and
17-OCH3), 3.89 (1H, ddd, J¼3.7, 3.1, 2.4 Hz, 1-H), 3.71
(1H, dd, J¼11.3, 3.1 Hz, 22-H), 3.48 (1H, dd, J¼11.3,
3.7 Hz, 22-H), 3.41 (1H, dd, J¼7.6, 2.4 Hz, 13-H), 3.17
(1H, ddd, J¼11.6, 2.6, 2.4 Hz, 3-H), 2.92 (1H, dd, J¼17.4,
2.4 Hz, 4-Ha), 2.82 (1H, dd, J¼21.1, 7.6 Hz, 14-Ha), 2.30
(3H, s, NCH3), 2.27 (1H, d, J¼21.1 Hz, 14-Hb), 1.93 (6H, s,
6-CH3 and 16-CH3), 1.42 (1H, ddd, J¼17.4, 11.6, 2.4 Hz,
4-Hb); 13C NMR (CDCl3, 125 MHz) d 186.3 (s, C-15),
185.5 (s, C-5), 182.3 (s, C-18), 181.4 (s, C-8), 155.5 (s, C-7),
155.4 (s, C-17), 141.7 (s, C-20), 141.4 (s, C-10), 136.1 (s,
C-9), 135.6 (s, C-19), 128.8 (s, C-6), 128.6 (s, C-16), 116.9
(s, CN), 64.2 (t, C-22), 61.1 (q, OCH3), 61.0 (q, OCH3), 59.1
(d, C-21), 58.0 (d, C-1), 54.5 (d, C-13), 54.3 (d, C-3), 54.2
(d, C-11), 41.5 (q, NCH3), 25.4 (t, C-4), 21.5 (t, C-14), 8.7
(q, 6-CH3), 8.7 (q, 16-CH3); FAB-MS (Magic bullet) m/z
(%) 494 (Mþþ1, 8), 309 (20), 220 (15), 155 (59), 154 (17),
152 (13), 137 (10), 135 (24), 121 (13), 118 (100), 102 (42),
101 (14), 89 (15), 87 (12), 85 (77), 69 (12), 55 (14); HR-
FABMS m/z 494.1910 [Mþþ1] (calcd for C26H28N3O7,
494.1927).
1.1.2. 6,7,9,14,14a,15-Hexahydro-9-(hydroxymethyl)-
2,11-dimethoxy-3,12,16-trimethyl-(6S,9R,14aS,15R)-
(2)-6,15-imino-4H-isoquino[3,2-b][3]benzazocine-
1,4,10,13(9H)-tetrone (5). [a]2D5¼2109.8 (c 0.2, CHCl3);
CD D 1 nm (c 129.6 mM, methanol, 24 8C) 22.5 (346),
21.4 (300), 29.1 (281), þ1.9 (254), 21.3 (230), 20.6
(223); IR (CHCl3) 2943, 1656, 1615, 1450, 1376, 1311,
1237, 1153 cm21; UV lmax (log 1) 269 (4.35), 370 (3.14)
1
nm; H NMR (CDCl3, 270 MHz) d 4.06 (1H, dd, J¼2.7,
0.5 Hz, 11-H), 4.01, 3.96 (each, 3H, s, 7-OCH3 and
17-OCH3), 3.75 (1H, dd, J¼11.2, 3.7 Hz, 22-H), 3.52 (1H,
dd, J¼11.2, 1.0 Hz, 22-H), 3.51 (1H, ddd, J¼3.7, 2.9,
1.0 Hz, 1-H), 3.18 (1H, m, 13-H), 3.03 (1H, dd, J¼11.0,
2.4 Hz, 21-Hb), 2.81 (1H, ddd, J¼11.7, 2.7, 2.4 Hz, 3-H),
2.81 (1H, dd, J¼18.1, 2.4 Hz, 4-Ha), 2.80 (1H, dd, J¼11.0,
2.4 Hz, 21-Ha), 2.80 (1H, dd, J¼21.0, 7.6 Hz, 14-Ha), 2.26
(3H, s, NCH3), 2.24 (1H, d, J¼21.0 Hz, 14-Hb), 1.94, 1.92
(each 3H, s, 6-CH3 and 16-CH3), 1.41 (1H, ddd, J¼18.1,
11.7, 2.9 Hz, 4-Hb); 13C NMR (CDCl3, 67.5 MHz) d 185.9
(s, C-15), 185.8 (s, C-5), 182.6 (s, C-18), 182.1 (s, C-8),
155.6 (s, C-7), 155.5 (s, C-17), 142.8 (s, C-20), 142.0 (s,
C-10), 137.3 (s, C-9), 136.3 (s, C-19), 128.8 (s, C-6), 128.6
1.1.4. 9-[(Acetoxy)methyl]-6,7,9,14,14a,15-hexahydro-7-
hydroxy-2,11-dimethoxy-3,12,16-trimethyl-(6S,7S,
9R,14aS,15R)-(2)-6,15-imino-4H-isoquino[3,2-b][3]-
benzazocine-1,4,10,13(5H)-tetrone
(jorumycin:
2).
Compound 6 (28.5 mg, 0.053 mmol) was dissolved in a
mixture of acetonitrile and water [3:2 (v/v), 5 ml], and silver
nitrate (225.1 mg, 1.33 mmol) was added. After stirring at
40 8C for 2 h, the reaction mixture was filtered and then
washed with chloroform (50 ml), and the combined filtrates
were concentrated in vacuo. The residue was diluted with
water (20 ml) and extracted with chloroform (20 ml£3).
The combined extracts were washed with brine (20 ml),