H. Kikuchi et al. / Tetrahedron 65 (2009) 469–477
475
(3H, s), 3.00 (1H, dd, J¼12.8, 11.6 Hz), 2.80 (1H, dd, J¼12.8, 4.4 Hz),
2.66–2.75 (1H, m), 2.53 (1H, dd, J¼11.6, 4.4 Hz), 2.39 (2H, t,
J¼7.3 Hz), 2.18–2.33 (2H, m), 2.02–2.12 (1H, m), 1.93 (3H, s), 1.82–
1.99 (4H, m), 1.76 (3H, s), 1.70 (3H, s), 1.67 (3H, s), 1.55–1.73 (3H, m),
1.19–1.44 (12H, m), 1.03 (3H, s), 0.99 (3H, s), 0.83 (3H, t, J¼7.0 Hz);
J¼12.9, 11.8 Hz), 2.79 (1H, dd, J¼12.9, 4.3 Hz), 2.69 (1H, td, J¼13.4,
5.3 Hz), 2.51 (1H, dd, J¼11.8, 4.3 Hz), 2.29–2.37 (1H, m), 2.12 (3H,
s), 2.05–2.28 (3H, m), 1.94 (3H, s), 1.79–1.95 (3H, m), 1.77 (3H, s),
1.69 (3H, s), 1.67 (3H, s), 1.57 (1H, m), 1.30–1.48 (5H, m), 1.08 (3H,
d, J¼7.0 Hz), 1.04 (3H, d, J¼7.0 Hz), 1.01 (3H, s), 0.95 (3H, s); 13C
13C NMR (100 MHz, pyridine-d5)
d
173.2, 166.5, 164.8, 156.0, 148.9,
NMR (125 MHz, pyridine-d5) d 170.7, 169.5, 166.4, 164.8, 156.1,
131.2, 125.0, 114.7, 110.5, 109.0, 99.7, 75.6, 57.9, 55.4, 40.3, 39.5, 38.1,
37.8, 34.8, 34.3, 31.8, 31.2, 29.3, 29.2, 25.8, 25.5, 24.5, 23.3, 23.2, 22.9,
22.8, 22.1, 18.6, 17.5, 17.1, 14.2, 10.9; EIMS m/z 598 [M]þ, 454, 409,
373, 327, 299, 258, 197, 185, 153 (base); HREIMS m/z 598.4212
(598.4233 calcd for C37H58O6).
148.8, 131.2, 124.9, 114.7, 110.5, 109.0, 99.7, 77.5, 77.1, 57.9, 55.4,
40.3, 39.3, 37.8, 37.7, 34.2, 31.2, 30.4, 25.8, 24.4, 23.3, 23.1, 22.8,
22.0, 20.4, 18.9, 18.6, 17.7, 17.2, 17.1, 10.9; EIMS m/z 614 [M]þ, 569,
409, 153 (100%); HREIMS m/z 614.3799 (614.3819 calcd for
C36H54O8).
((1S,2S,4aR,5R,8aR)-5-((4-(Methoxymethoxy)-5,6-dimethyl-2-
oxo-2H-pyran-3-yl)methyl)-1,4a-dimethyl-6-methylene-1-(4-methyl-
pent-3-enyl)decahydronaphthalen-2-yl) cyclohexylacetate (8e):
4.8. ((1S,2S,4aR,5R,8aR)-5-((4-Hydroxy-5,6-dimethyl-2-oxo-
2H-pyran-3-yl)methyl)-1,4a-dimethyl-6-methylene-1-(4-
methylpent-3-enyl)decahydronaphthalen-2-yl) (R)-2-acetoxy-
3-methylbutanoate (metarhizin B (2))
colorless oil; 1H NMR (500 MHz, pyridine-d5)
d 5.17–5.21 (1H, m),
5.12–5.16 (1H, m), 5.15 (1H, d, J¼5.9 Hz), 5.08 (1H, d, J¼5.9 Hz), 4.69
(1H, br s), 4.55 (1H, br s), 3.60 (3H, s), 2.99 (1H, dd, J¼12.9, 11.7 Hz),
2.80 (1H, dd, J¼12.9, 4.4 Hz), 2.66–2.74 (1H, m), 2.54 (1H, dd, J¼11.7,
4.4 Hz), 2.18–2.30 (2H, m), 2.26 (2H, d, J¼7.1 Hz), 2.02–2.10 (1H, m),
1.82–1.97 (5H, m), 1.94 (3H, s), 1.71–1.79 (2H, m), 1.77 (3H, s), 1.71
(3H, s), 1.67 (3H, s), 1.51–1.65 (4H, m), 1.31–1.42 (4H, m), 1.16–1.26
(2H, m), 1.04 (3H, s), 1.02–1.10 (1H, m), 1.00 (3H, s), 0.93–0.98 (2H,
To a solution of 7 (5.5 mg, 8.9
mmol) in MeOH (2.0 mL) was
added 28% sodium methoxide in MeOH (10
mL). After being stirred
for 2 h at room temperature, the reaction mixture was neutralized
with Dowex 50w (Hþ form). The solvent was evaporated off, and
the residue was resolved in 15 mM hydrogen chloride solution in
MeOH (1.0 mL) at 0 ꢁC. After being stirred for 3 h, this solution was
poured into saturated sodium bicarbonate solution and extracted
with EtOAc three times. The combined organic layer was washed
with brine, dried over sodium sulfate, and evaporated. The residue
was subjected to recycle preparative HPLC (column, JAIGEL-GS310
m); 13C NMR (125 MHz, pyridine-d5)
d 172.4, 166.4, 164.8, 156.0,
148.9,131.1,125.0,114.7,110.5,109.0, 99.7, 75.6, 57.9, 55.4, 42.6, 40.3,
39.5, 38.1, 37.8, 35.3, 34.3, 33.2, 33.1, 31.3, 26.4, 26.33, 26.30, 25.8,
24.5, 23.4, 23.2, 22.9, 22.1, 18.6, 17.6, 17.2, 10.9; EIMS m/z 596 [M]þ,
409, 373, 327, 299, 258, 197, 153 (base); HREIMS m/z 596.4084
(596.4077 calcd for C37H56O6).
((1S,2S,4aR,5R,8aR)-5-((4-(Methoxymethoxy)-5,6-dimethyl-2-
oxo-2H-pyran-3-yl)methyl)-1,4a-dimethyl-6-methylene-1-(4-methyl-
pent-3-enyl)decahydronaphthalen-2-yl) 3-methylbutanoate (8f):
(
f
20.0 mmꢂ500 mm); solvent, EtOAc) to give 2 (3.0 mg, 5.6
63% from 7).
Synthetic 2: [
mmol,
a
]
ꢀ41.4 (c 0.30, pyridine); other spectral data
D
colorless oil; 1H NMR (400 MHz, pyridine-d5)
d
5.17–5.23 (1H, m),
were identical with those of the natural 2.
5.12 (1H, m), 5.09 (1H, d, J¼6.0 Hz), 5.07 (1H, d, J¼6.0 Hz), 4.68
(1H, br s), 4.54 (1H, br s), 3.59 (3H, s), 2.99 (1H, dd, J¼13.0, 11.6 Hz),
2.80 (1H, dd, J¼13.0, 4.4 Hz), 2.69 (1H, td, J¼13.6, 5.3 Hz), 2.52
(1H, dd, J¼11.6, 4.4 Hz), 2.04–2.25 (6H, m), 1.94 (3H, s), 1.78–1.93
(4H, m), 1.77 (3H, s), 1.69 (3H, s), 1.66 (3H, s), 1.57–1.63 (1H, m),
1.33–1.42 (4H, m), 1.03 (3H, s), 0.98 (3H, s), 0.93 (6H, d, J¼6.5 Hz);
In similar procedure, compounds 9g (yield 64%) and 9h (77%)
were prepared from 8g and 8h, respectively.
((1S,2S,4aR,5R,8aR)-5-((4-Hydroxy-5,6-dimethyl-2-oxo-2H-pyran-
3-yl)methyl)-1,4a-dimethyl-6-methylene-1-(4-methylpent-3-enyl)de-
cahydronaphthalen-2-yl) (2R)-2-hydroxybutanoate (9g): colorless
amorphous solid; 1H NMR (400 MHz, pyridine-d5)
d 5.13 (1H, dd,
13C NMR (100 MHz, pyridine-d5)
d
172.4, 166.4, 164.8, 156.0,
J¼8.9, 7.0 Hz), 5.01–5.06 (1H, m), 4.74 (1H, br s), 4.67 (1H, br s), 4.50
(1H, dd, J¼6.9, 5.0 Hz), 3.23 (1H, dd, J¼13.0, 11.2 Hz), 2.97 (1H, dd,
J¼13.0, 4.5 Hz), 2.80–2.88 (1H, m), 2.66 (1H, dd, J¼11.2, 4.5 Hz),
2.21–2.26 (1H, m), 1.88–2.14 (6H, m), 1.98 (3H, s), 1.91 (3H, s), 1.76–
1.84 (2H, m), 1.61 (3H, s), 1.50–1.60 (1H, m), 1.54 (3H, s), 1.25–1.44
(4H, m), 1.15 (3H, t, J¼7.4 Hz), 1.03 (3H, s), 0.94 (3H, s); 13C NMR
148.9, 131.2, 125.0, 114.7, 110.5, 109.0, 99.7, 75.6, 57.9, 55.4, 43.8,
40.3, 39.5, 38.1, 37.8, 34.3, 31.3, 26.0, 25.8, 24.5, 23.3, 23.2, 22.9, 22.4,
22.3, 22.1, 18.6, 17.6, 17.2, 10.9; EIMS m/z 556 [M]þ, 511, 409,
258, 197, 153 (100%); HREIMS m/z 556.3754 (556.3764 calcd for
C34H52O6).
((1S,2S,4aR,5R,8aR)-5-((4-(Methoxymethoxy)-5,6-dimethyl-2-
oxo-2H-pyran-3-yl)methyl)-1,4a-dimethyl-6-methylene-1-(4-methyl-
pent-3-enyl)decahydronaphthalen-2-yl) (2R)-2-acetoxybutanoate
(100 MHz, pyridine-d5) d 174.8, 165.9, 165.3, 155.0, 149.3, 130.9,
125.1, 110.1, 107.3, 103.6, 76.5, 72.3, 55.5, 40.4, 39.7, 38.2, 38.0, 34.3,
31.6, 28.5, 25.9, 24.6, 23.4, 23.2, 22.9, 22.2, 18.5, 17.6, 17.3, 11.1, 10.0;
EIMS m/z 514 [M]þ, 411, 395, 329, 299, 258, 243, 153 (100%);
HREIMS m/z 514.3286 (514.3294 calcd for C31H46O6).
(8g): colorless oil; 1H NMR (400 MHz, pyridine-d5)
d 5.22–5.29 (1H,
m), 5.13–5.17 (2H, m), 5.09 (1H, d, J¼6.2 Hz), 5.07 (1H, d, J¼6.2 Hz),
4.67 (1H, br s), 4.53 (1H, br s), 3.59 (3H, s), 2.97 (1H, dd, J¼13.0,
11.6 Hz), 2.77 (1H, dd, J¼13.0, 4.2 Hz), 2.67 (1H, td, J¼13.0, 6.8 Hz),
2.51 (1H, dd, J¼11.6, 4.2 Hz), 2.15–2.30 (2H, m), 2.05–2.15 (1H, m),
2.10 (3H, s), 1.92–1.97 (1H, m), 1.94 (3H, s), 1.81–1.92 (3H, m), 1.77
(3H, s), 1.70 (3H, s), 1.68 (3H, s), 1.30–1.60 (7H, m), 1.01 (3H, t,
J¼7.4 Hz), 1.00 (3H, s), 0.95 (3H, s); 13C NMR (100 MHz, pyridine-d5)
((1S,2S,4aR,5R,8aR)-5-((4-Hydroxy-5,6-dimethyl-2-oxo-2H-pyran-
3-yl)methyl)-1,4a-dimethyl-6-methylene-1-(4-methylpent-3-enyl)de-
cahydronaphthalen-2-yl) (2S)-2-hydroxy-3-methylbutanoate (9h):
colorless amorphous solid; 1H NMR (400 MHz, pyridine-d5)
d 5.16
(1H, dd, J¼8.8, 7.1 Hz), 5.08–5.12 (1H, m), 4.74 (1H, br s), 4.66 (1H, br
s), 4.35 (1H, d, J¼4.2 Hz), 3.22 (1H, dd, J¼13.0, 11.4 Hz), 2.96 (1H,
dd, J¼13.0, 4.5 Hz), 2.80–2.89 (1H, m), 2.64 (1H, dd, J¼11.4, 4.5 Hz),
2.30–2.38 (1H, m), 2.21–2.26 (1H, m), 2.05–2.17 (1H, m), 1.90–2.04
(3H, m), 1.97 (3H, s), 1.91 (3H, s), 1.75–1.84 (2H, m), 1.64 (3H,
s), 1.53–1.62 (1H, m), 1.55 (3H, s), 1.31–1.44 (3H, m), 1.24–1.31 (1H,
m), 1.18 (3H, d, J¼6.8 Hz), 1.13 (3H, d, J¼6.8 Hz), 1.03 (3H, s), 0.97
d
170.4, 170.1, 166.4, 164.7, 156.1, 148.8, 131.1, 125.1, 114.7, 110.5,
109.0, 99.7, 77.0, 73.9, 57.9, 55.3, 40.3, 39.4, 37.8, 37.7, 34.1, 31.2, 25.8,
24.8, 24.3, 23.3, 23.1, 22.9, 22.1, 20.4, 18.4, 17.6, 17.1, 10.9, 9.5; EIMS
m/z 600 [M]þ, 555, 409, 153 (100%); HREIMS m/z 600.3647
(600.3662 calcd for C35H52O8).
((1S,2S,4aR,5R,8aR)-5-((4-(Methoxymethoxy)-5,6-dimethyl-2-
oxo-2H-pyran-3-yl)methyl)-1,4a-dimethyl-6-methylene-1-(4-methylpent-
3-enyl)decahydronaphthalen-2-yl) (2S)-2-acetoxy-3-methylbutanoate
(3H, s); 13C NMR (100 MHz, pyridine-d5)
d 174.5, 165.9, 165.3, 155.0,
149.3, 130.9, 125.0, 110.1, 107.2, 103.6, 76.4, 76.3, 55.5, 40.3, 39.4,
38.0, 37.8, 34.1, 32.6, 31.5, 25.8, 24.5, 23.3, 23.0, 22.8, 22.0, 19.6, 18.7,
17.7, 17.1,16.9,10.9; EIMS m/z 528 [M]þ, 426, 410, 395, 329, 299, 258,
243, 153 (100%); HREIMS m/z 528.3444 (528.3451 calcd for
C32H48O6).
(8h): colorless oil; 1H NMR (500 MHz, pyridine-d5)
d 5.14–5.26
(2H, m), 5.08–5.11 (1H, m), 5.09 (1H, d, J¼5.9 Hz), 5.07 (1H, d,
J¼5.9 Hz), 4.67 (1H, br s), 4.53 (1H, br s), 3.59 (3H, s), 2.97 (1H, dd,