The β-epoxy ketone 12: colorless prisms from EtOAc, mp
221–222 ЊC; νmax 1715, 1692; δH 7.71 (1H, s, H-14), 6.60 (1H, s,
H-17), 6.41 (1H, s, H-7), 4.53 (1H, d, J 4.3, H-2), 4.11 (1H, ddd,
J 13.0, 6.3, 4.5, Hβ-10), 3.78 (1H, d, J 4.3, H-1), 3.26 (1H, ddd,
J 13.0, 9.1, 5.2, Hα-10), 3.20, 2.94 (each 1H, d, J 16.7, H-4), 3.04
(1H, ddd, J 16, 9.1, 6.3, Hβ-11), 2.72 (1H, ddd, J 16.0, 5.2, 4.5,
Hα-11); m/z (EI) 327 (Mϩ, 56%), 298 (100) (Found: C, 65.75; H,
5.24; N, 4.14%).
100 mg, 2.35 mmol) and imidazole (3 mg, 0.04 mmol) in THF
(20 ml) was heated at reflux for 1 h under a nitrogen atmos-
phere. CH3I (95%; 6 ml, 40 mmol) and Bu4NHSO4 (50 mg,
0.15 mmol) were added to the cooled mixture and the mixture
heated at reflux for a further 2 h. After removal of the precipi-
tates by filtration, the filtrate was acidified with 1% aq. HCl
and extracted with CHCl3. The product was chromatographed
(EtOAc) to give 16 (31 mg). The precipitate (sodium salt of 4)
was remethylated as described above to give a further crop of
16 (69 mg) (total yield: 100 mg, 62%). The 3α-methoxy-1,2α-
epoxide 16 crystallized in colorless needles from EtOAc, mp
169–170 ЊC; νmax 1685; δH 6.74 (1H, s, H-14), 6.59 (1H, s, H-17),
6.49 (1H, s, H-7), 4.27 (1H, d, J 3.9, H-1), 3.93 (1H, ddd, J 12.7,
8.5, 7.3, Hβ-10), 3.87, 3.84 (each 3H, s, 2 × OMe), 3.83 (1H, dd,
J 3.9, 1.9, H-2), 3.73 (1H, ddd, J 11.1, 5.3, 1.9, H-3), 3.56 (1H,
ddd, J 12.7, 7.3, 5.0, Hα-10), 3.40 (3H, s, OMe), 3.08 (1H, ddd,
J 16.0, 8.5, 7.3, Hα-11), 2.97 (1H, ddd, J 16.0, 7.3, 5.0, Hβ-11),
2.38 (1H, dd, J 12.0, 5.3, Hβ-4), 1.58 (1H, dd, J 12, 11.1, Hα-4);
m/z (EI) 343 (Mϩ, 98%), 257 (100) (Found: Mϩ, 343.1427; C,
66.16; H, 6.18; N, 3.97. C19H21NO5 requires M, 343.1418; C,
66.46; H, 6.16; N, 4.08%).
Reduction of the ꢀ-epoxy ketone 11
(1) With reagent A. NaBH4 (33 mg, 1.22 mmol) was added to
a mixture of 11 (200 mg, 0.61 mmol) and CeCl3ؒ7H2O (330 mg,
1.22 mmol) in MeOH (20 ml) at 0 ЊC. The mixture was stirred
for 10 min at 0 ЊC. After decomposition of excess of hydride
with ice, the mixture was extracted with CHCl3. The products
were separated by MPLC (CHCl3–MeOH 9:1) to give the 1,2α-
epoxy-3β-alcohol 13 (142 mg, 71%) and the 1,2α-epoxy-3α-
alcohol 4 (27 mg, 13%).
(2) With reagent B. Bu4NBH4 (24 mg, 0.36 mmol) was added
to a solution of 11 (30 mg, 0.09 mmol) in MeOH (6 ml) at 0 ЊC.
The mixture was stirred for 15 h at 0 ЊC and worked up as
described above to afford the 1,2α-epoxy-3β-alcohol 13 (32 mg,
100%) as colorless prisms, mp 244–246 ЊC (from EtOAc); νmax
3430, 1715, 1693; δH (CDCl3–CD3OD 3:1) 6.91 (1H, s, H-14),
6.73 (1H, s, H-17), 6.45 (1H, s, H-7), 4.39 (1H, m, H-3), 4.27
(1H, d, J 3.2, H-1), 3.87 (1H, ddd, J 13.0, 8.6, 7.2, Hβ-10), 3.86
(6H, s, 2 × OCH3), 3.64 (1H, br d, J 3.2, H-2), 3.54 (1H, ddd,
J 13.0, 6.9, 4.8, Hα-10), 3.08 (1H, ddd, J 16.2, 8.6, 6.9, Hβ-11),
2.98 (1H, ddd, J 16.2, 7.2, 4.8, Hα-11), 2.47 (1H, d, J 14.1,
Hβ-4), 1.80 (1H, dd, J 14.1, 4.9, Hα-4); m/z (EI) 329 (Mϩ,
93%), 257 (100) (Found: C, 65.65; H, 5.85; N, 4.14. C18H19NO5
requires C, 65.64; H, 5.82; N, 4.25%).
( )-8-Oxoerythratidine 17
A 0.1 M solution of SmI2 in THF (2 ml, 0.2 mmol) was added
to a solution of 16 (35 mg, 0.10 mmol) in THF (2 ml)–MeOH
(1 ml) at Ϫ90 ЊC and the mixture was stirred for 5 min at the
same temperature. The reaction was quenched by addition of
pH 8 phosphate buffer, and the mixture was extracted with
CHCl3. Purification of the product by PTLC (CHCl3–MeOH
14:1) gave ( )-8-oxoerythratidine 17 (26 mg, 74%) as colorless
prisms, mp 183–185 ЊC (from EtOAc); νmax 3375, 1703, 1681;
δH 6.68 (1H, s, H-17), 6.48 (1H, s, H-14), 6.06 (1H, dd, J 3.6, 2.4,
H-1), 4.53 (1H, ddd, J 4.3, 3.6, 2.4, H-2), 4.24 (1H, ddd, J 13.1,
8.7, 5.7, Hβ-10), 3.86, 3.82 (each 3H, s, 2 × OMe), 3.55 (1H,
ddd, J 12.8, 4.3, 3.6, H-3), 3.42 (1H, ddd, J 13.1, 8.6, 6.5, Hα-
10), 3.35 (3H, s, OMe), 3.04 (1H, ddd, J 16.3, 8.7, 6.5, Hα-11),
3.01 (1H, d, J 19.4, Hα-7), 2.97 (1H, ddd, J 16.3, 8.6, 5.7,
Hβ-11), 2.91 (1H, dt, J 19.4, 2.4, Hβ-7), 2.21 (1H, dd, J 11.5,
3.6, Hβ-4), 1.99 (1H, dd, J 12.8, 11.5, Hα-4); m/z (EI) 345 (Mϩ,
30%), 287 (100) (Found: C, 65.77; H, 6.71; N, 3.98. C19H23NO5
requires C, 66.07; H, 6.71; N, 4.06%).
Reduction of the ꢁ-epoxy ketone 12
(1) With reagent A. The reduction of 12 (20 mg, 0.06 mmol)
with NaBH4 (3.3 mg, 0.12 mmol) and CeCl3ؒ7H2O (33 mg, 0.12
mmol) in MeOH (6 ml) was carried out and worked up as
described for 11 to give a mixture (14 mg, 70%) of the 3β-
alcohol 14 and the 3α-alcohol 15 (14:15 = 5:2, determined by
1H NMR), which were separated by RHPLC (CHCl3).
(2) With reagent B. The reduction of 12 (33 mg, 0.101 mmol)
with Bu4NBH4 (26 mg, 0.404 mmol) in MeOH (10 ml) as
described for 11 gave a mixture (32.5 mg, 98%) of 14 and 15
(14:15 3:1, determined by 1H NMR).
The 1,2β-epoxy-3β-alcohol 14: Colorless needles, mp 236–
237 ЊC (from EtOAc); νmax 3405, 1657; δH (CDCl3–CD3OD 3:1)
7.72 (1H, s, H-14), 6.58 (1H, s, H-17), 6.25 (1H, s, H-7), 4.27
(1H, d, J 4.7, H-1), 4.05 (1H, m, H-3), 4.03 (1H, ddd, J 13.1,
6.8, 4.5, Hβ-10), 3.91, 3.84 (each 3H, s, 2 × OMe), 3.81 (1H, br
d, J 4.7, H-2), 3.34 (1H, ddd, J 13.1, 8.9, 5.4, Hα-10), 3.01 (1H,
ddd, J 16.2, 8.9, 6.8, Hβ-11), 2.77 (1H, ddd, J 16.2, 5.4, 4.5,
Hα-11), 2.35 (1H, dd, J 14.2, 9.2, Hα-4), 2.26 (1H, dd, J 14.2,
5.6, Hβ-4); m/z (EI) 329 (Mϩ, 98%), 257 (100) (Found: C, 65.43;
H, 5.85; N, 4.01%).
The 1,2β-epoxy-3α-alcohol 15: Colorless prisms, mp 227–
230 ЊC (from EtOAc); νmax 3405, 1657; δH (CDCl3–CD3OD 3:1)
7.48 (1H, s, H-14), 6.66 (1H, s, H-17), 6.47 (1H, s, H-7), 4.17
(1H, d, J 3.9, H-1), 4.08 (1H, dd, J 9.8, 5, H-3), 3.87, 3.85 (each
3H, s, 2 × OCH3), 3.86 (1H, ddd, J 12.3, 8.4, 6.8, Hβ-10), 3.68
(1H, br d, J 3.9, H-2), 3.55 (1H, ddd, J 12.3, 6.7, 5.8, Hα-10),
3.04 (1H, ddd, J 15.8, 8.4, 6.7, Hβ-11), 2.98 (1H, ddd, J 15.8,
6.8, 5.8, Hα-11), 2.60 (1H, dd, J 12.7, 5.0, Hβ-4), 1.77 (1H, dd,
J 12.7, 9.8, Hα-4); m/z (EI) 329 (Mϩ, 96%), 257 (100) (Found:
Mϩ, 329.1267. C18H19NO5 requires M, 329.1262).
AlH3 Reduction of 17
A solution of AlH3 (2.5 ml) [prepared from LiAlH4 (42 mg, 1.11
mmol) and AlCl3 (48 mg, 0.36 mmol) in Et2O (6 ml)] was added
to a solution of 17 (33 mg, 0.10 mmol) in THF (3 ml) at 0 ЊC.
The mixture was stirred for 3.5 h at 0 ЊC under a nitrogen
atmosphere. Reaction was quenched with ice–water, and the
mixture was basified (pH 12) by addition of 28% NH4OH
and extracted with diethyl ether. The extract was dried over
K2CO3 and concentrated in vacuo to give a mixture of
( )-erythratidine 1 and ( )-erysotrine 2 (10 mg, 1:2 = 1:1,
determined by 1H NMR). The aqueous layer was extracted with
CHCl3 and concentated to dryness to give another crop of 1
(20.4 mg). Yield of 1 was 25.5 mg (80%) and that of 2 was 4.9 mg
(16%).
( )-Erythratidine 1: a pale yellow gum, δH 6.62 (1H, s, H-17),
6.49 (1H, s, H-14), 5.85 (1H, m, H-1), 4.48 (1H, m, H-2), 3.86,
3.80 (each 3H, s, 2 × OMe), 3.69 (1H, ddd, J 12.8, 4.3, 3.7,
H-3), 3.51 (1H, ddd, J 14.3, 11.0, 7.2, Hβ-10), 3.36 (3H, s,
OMe), 3.15 (1H, dd, J 14.3, 8.0, 1.4, Hα-10), 3.00 (1H, ddd,
J 17.1, 11.0, 8.0, Hα-11), 2.95 (1H, td, J 9.0, 2.8, Hβ-8), 2.67 (1H,
td, J 9.0, 7.0, Hα-8), 2.58 (1H, ddd, J 17.1, 7.2, 1.4, Hβ-11), 2.48
(1H, dtd, J 16.0, 9.0, 1.5, Hα-7), 2.24 (1H, m, Hβ-7), 2.06 (1H,
dd, J 11.3, 3.7, Hβ-4), 1.82 (1H, dd, J 12.8, 11.3, Hα-4); m/z (EI)
331 (Mϩ, 6%), 300 (14), 274 (18), 273 (100), 272 (20), 258 (24),
257 (95), 256 (31), 244 (47), 242 (14), 149 (11), 83 (11) (Found:
Mϩ, 331.1787. Calc. for C19H25NO4: M, 331.1782). The picrate
crystallized in yellow prisms, mp 217–219 ЊC (from acetone)
6,7-Didehydro-1,2ꢀ-epoxy-3ꢀ,15,16-trimethoxy-8-oxoerythrinan
16
A mixture of 4 (156 mg, 0.47 mmol), NaH (60% oil dispersion;
1510
J. Chem. Soc., Perkin Trans. 1, 2000, 1505–1511