908
B. Zhou et al. / Tetrahedron 67 (2011) 904e909
þ
þ
4
4
06 (M , 30), 309 (100); HRMS (EI) calcd for C21
06.1144, found 406.1153.
H27BrO
3
(M ):
nitrate (320 mg, 0.585 mmol) and the mixture was stirred at room
temperature for 5 h. The solvent was evaporated, then CH Cl was
added and the mixture was washed with water and brine. The or-
ganic phase was dried over Na SO and concentrated to give a crude
2
2
4.1.8. 2
b
-Hydroxyl triptophenolide methyl ether (4). To a solution of
2
4
compound 13 (25 mg, 0.06 mmol) in THF (3 mL), t-BuOH (3 mL) and
O (1 mL) were added 2-methyl-2-butene (0.25 mL), NaH
PO .2H O (47 mg, 0.3 mmol) and NaClO (27 mg, 0.3 mmol). The
mixture was stirred at room temperature for 3 h and the solvent
was evaporated, then AcOEt was added and the mixture was
product, which was chromatographed on silica gel (20% EtOAc in n-
hexane) to give pure 17 (104.4 mg, 89%) as a colourless solid, H NMR
1
H
2
2
-
4
2
2
(CDCl
3
, 300 MHz)
d
7.26e7.15 (m, 2H), 5.09 (d, J¼4.2 Hz, 1H), 5.01 (d,
J¼6.9 Hz,1H), 4.84 (m, 3H), 4.60 (d, J¼4.8 Hz,1H), 3.88 (s, 3H), 3.53 (s,
3H), 3.28 (sept, J¼7.2 Hz, 1H), 3.10 (br s, 1H), 3.02 (d, J¼12.9 Hz, 1H),
2.75 (d, J¼14.4 Hz, 1H), 2.20e2.03 (m, 2H), 1.85 (dd, J¼14.4, 5.4 Hz,
2 4
washed with brine. The organic layer was dried over Na SO and
concentrated to give a crude product, which was chromatographed
13
1H),1.30 (d, J¼7.2 Hz, 3H),1.18 (d, J¼7.2 Hz, 3H),1.16 (s, 3H); C NMR
on silica gel (15% EtOAc in n-hexane) to give pure 4 (17.4 mg, 85%) as
3
(CDCl ,100 MHz) d 172.7, 166.1, 156.2, 143.7, 139.8, 129.8, 126.9, 125.9,
ꢁ
25
a colourless solid, mp 192e194 C; [
(
a]
D
þ30 (c 0.06, CH
2
Cl
2
); IR
120.9, 96.5, 70.2, 65.3, 62.7, 62.2, 55.9, 40.3, 37.1, 36.0, 28.0, 26.1, 24.3,
ꢀ
1
1
þ
KBr) 3477, 2962, 2931, 1749, 1675, 1033 cm
,
H NMR (CDCl
3
,
23.7, 23.3; LRMS (EI, 70 eV) m/z (%) 402 (M , 44), 309 (100); HRMS
þ
3
3
2
00 MHz)
d
7.14 (m, 2H), 4.88 (m, 2H), 4.75 (d, J¼7.5 Hz, 1H), 3.73 (s,
(EI) calcd for C23H O
30 6
(M ): 402.2042, found 402.2028.
H), 3.29 (sept, J¼3.9 Hz,1H), 3.14e2.85 (m, 2H), 2.75e2.60 (m, 2H),
.04e1.90 (m, 3H), 1.24 (d, J¼3.9 Hz, 3H), 1.21 (d, J¼3.9 Hz, 3H), 1.18
4.1.12. (3bR,9bS,11S)-7-isopropyl-6-methoxy-11-(methoxymethoxy)-
9b-methyl-3b,4,10,11-tetrahydrophenanthro[2,1-c]furan-1,5
(3H,9bH)-dione (18). To a solution of compound 17 (38 mg,
(
s, 3H); 13C NMR (CDCl
3
, 100 MHz) d 173.7, 165.2, 155.3, 143.8, 139.1,
1
2
27.5, 126.6, 124.3, 120.7, 70.6, 60.5, 60.3, 41.9, 41.5, 36.0, 26.1, 24.0,
þ
3.9, 23.7, 22.9, 19.5; LRMS (EI, 70 eV) m/z (%) 342 (M , 100); HRMS
2 2
0.094 mmol) in anhydrous CH Cl (3 mL) were added pyridinium
þ
(
EI) calcd for C21
H
26
O
4
(M ): 342.1831, found 342.1829.
dichromate (70.6 mg, 0.188 mol) and molecular sieves 4 A (120 mg).
The mixture was stirred at room temperature overnight, diluted
with ethyl acetate, and filtered through a pad of silica gel. The fil-
trate was concentrated under reduced pressure to give a crude
product, which was chromatographed on silica gel (15% EtOAc in
n-hexane) to give pure 18 (36.5 mg, 97%) as a colourless solid, mp
4
.1.9. (3bR,5R,9bS,11S)-5,11-dihydroxy-7-isopropyl-6-methoxy-9b-
methyl-3b,4,5,9b,10,11-hexahydrophenanthro[2,1-c]furan-1(3H)-one
14). To a solution of 4 (100 mg, 0.292 mmol) in acetonitrile (4 mL)
and water (4 mL), was added ammonium ceric nitrate (320 mg,
(
ꢁ
1
0
3
.585 mmol) and the mixture was stirred at room temperature for
h. The solvent was evaporated, then CH Cl was added and the
106e108 C, H NMR (CDCl
3
, 400 MHz)
d
7.47 (d, J¼8.4 Hz, 1H), 7.19
2
2
(d, J¼8.4 Hz, 1H), 5.01 (d, J¼6.8 Hz, 1H), 4.83e4.81 (m, 3H), 4.65
(d, J¼5.6 Hz, 1H), 3.82 (s, 3H), 3.52 (s, 3H), 3.41 (sept, J¼7.2 Hz, 1H),
3.08 (dd, J¼14.0, 7.2 Hz, 1H), 2.80 (m, 3H), 1.97 (dd, J¼14.4, 5.2 Hz,
mixture was washed with water and brine. The organic phase was
dried over Na SO and concentrated to give a crude product, which
was chromatographed on silica gel (20% EtOAc in n-hexane) to give
2
4
1
3
1H), 1.29 (s, 3H), 1.25 (d, J¼7.2 Hz, 3H), 1.19 (d, J¼7.2 Hz, 3H);
C
1
pure 14 (84.6 mg, 81%) as a colourless solid, H NMR (CDCl
3
,
3
NMR (CDCl ,100 MHz) d 194.5,172.1,163.2,158.4,150.8,142.1,132.0,
3
2
3
2
00 MHz)
d
7.27e7.17 (m, 2H), 5.10e5.08 (m, 1H), 5.00e4.81 (m,
126.2, 124.4, 118.7, 96.5, 69.7, 64.4, 62.6, 55.9, 40.1, 39.2, 37.3, 36.1,
þ
H), 4.76 (d, J¼4.5 Hz, 1H), 3.88 (s, 3H), 3.28 (sept, J¼5.1 Hz, 1H),
.12 (br s, 1H), 3.05 (d, J¼8.7 Hz, 1H), 2.69 (d, J¼11.1 Hz, 1H),
.18e1.91 (m, 3H), 1.30 (d, J¼5.1 Hz, 3H), 1.18 (d, J¼5.1 Hz, 3H), 1.16
25.8, 23.7, 23.1, 23.1; LRMS (EI, 70 eV) m/z (%) 400 (M , 37), 385
þ
(100); HRMS (EI) calcd for C23
H
28
O
6
(M ): 400.1886, found
400.1871.
13
(
3
s, 3H); C NMR (CDCl , 100 MHz) d 173.6, 165.3, 156.1, 143.6, 139.8,
1
2
29.7, 127.1, 126.9, 121.3, 70.7, 62.7, 62.2, 60.3, 41.7, 36.9, 36.2, 27.9,
4.1.13. (3bR,9bS,11S)-6,11-dihydroxy-7-isopropyl-9b-methyl-
3b,4,10,11-tetrahydrophenanthro[2,1-c]furan-1,5(3H,9bH)-dione
(19). To a solution of 18 (25 mg, 0.062 mmol) in dichloromethane
þ
6.1, 24.3, 23.6, 23.3; LRMS (EI, 70 eV) m/z (%) 358 (M , 100); HRMS
þ
(
EI) calcd for C21
H
26
O
5
(M ): 358.1780, found 358.1780.
ꢁ
(
2 mL), under nitrogen at ꢀ78 C, was added BBr
3
(0.018 mL,
ꢁ
4
9
.1.10. (3bR,9bS,11S)-7-isopropyl-6-methoxy-11-(methoxymethoxy)-
b-methyl-3b,4,5,9b,10,11-hexahydrophenanthro[2,1-c]furan-1(3H)-
0.186 mol) and the mixture was stirred at ꢀ78 C for 1 h and
warmed to room temperature. An aqueous NaHCO
was added and the extracts were washed with brine. The organic
phase was dried over Na SO and concentrated to give a crude
3
solution (10%)
one (16). To a solution of compound 4 (26 mg, 0.076 mmol) in
CH Cl (3 mL) were added MOMCl (0.029 mL, 0.38 mol) and N,N-
2
2
2
4
Diisopropylethylamine (0.066 mL, 0.38 mmol). The mixture was
stirred at room temperature overnight and water (3 mL) was added.
The mixture was washed with water and brine. The organic phase
product, which was chromatographed on silica gel (20% EtOAc in n-
hexane) to give pure 19 (20.7 mg, 97%) as a white solid, H NMR
1
(CDCl
3
, 300 MHz)
d
13.04 (s,1H), 7.44 (d, J¼8.1 Hz,1H), 6.90 (d, J¼8.1
was dried over Na
2
SO
4
and concentrated to give a crude product,
Hz, 1H), 4.89e4.78 (m, 3H), 3.36 (sept, J¼6.6 Hz, 1H), 3.17e3.10 (m,
which was chromatographed on silica gel (7% EtOAc in n-hexane) to
1H), 2.89e2.73 (m, 3H), 2.62e2.60 (m, 1H), 2.06 (dd, J¼14.4, 6.3 Hz,
ꢁ
25
13
give pure 16 (26.9 mg, 92%) as a colourless solid, mp 90e92 C; [
þ35 (c 0.1, CH Cl ); IR (KBr) 3446, 2962, 2935, 2887, 1753, 1675,
H NMR (CDCl , 400 MHz) 7.12 (s, 2H), 5.01 (d,
a
]
D
1H), 1.31 (s, 3H), 1.25 (d, J¼6.6 Hz, 3H), 1.23 (d, J¼6.6 Hz, 3H);
C
2
2
3
NMR (CDCl ,100 MHz) d 201.8, 172.9, 162.0, 161.7,149.1, 135.9,133.9,
ꢀ
1 1
1027 cm
,
3
d
127.5, 114.2, 113.9, 70.1, 59.5, 40.7, 40.6, 36.0, 36.0, 26.1, 23.2, 22.1,
þ
J¼7.2 Hz, 1H), 4.84 (m, 3H), 4.59 (m, 1H), 3.73 (s, 3H), 3.54 (s, 3H),
22.0; LRMS (EI, 70 eV) m/z (%) 342 (M , 40), 327 (100); HRMS (EI)
þ
3
2
.29 (sept, J¼4.8 Hz, 1H), 3.10e2.89 (m, 2H), 2.78 (d, J¼14.4 Hz, 1H),
.60 (m, 1H), 2.00e1.82 (m, 3H), 1.23 (d, J¼4.8 Hz, 3H), 1.22 (d,
calcd for C20
22
H O
5
(M ): 342.1467, found 342.1467.
13
J¼4.8 Hz, 3H), 1.18 (s, 3H); C NMR (CDCl
3
, 100 MHz)
d
172.8, 166.0,
4.1.14. 7,8- -Epoxy-2
b
b,19-dihydroxy-14-oxo-18 (4/3)abeo-abieta-
1
5
7
C
55.4, 144.0, 139.2, 127.5, 125.5, 124.2, 120.2, 96.4, 70.1, 65.2, 60.5,
5.8, 41.6, 40.2, 35.7, 26.1, 23.9, 23.9, 23.8, 22.7, 19.5; LRMS (EI,
0 eV) m/z (%) 386 (M , 56), 326 (100); HRMS (EI) calcd for
3,9,12-trien-18-oic acid lactone (20). To a solution of 19 (30 mg,
ꢁ
0.088 mmol) in methanol (2 mL) at 0 C was added sodium boro-
þ
hydride (3.3 mg, 0.088 mmol) in three portions. After stirring at
þ
ꢁ
H
23 30
O
5
(M ): 386.2093, found 386.2107.
0 C for 30 min, the mixture was quenched with an aqueous NH
4
Cl
solution (10%) and extracted with EtOAc. The organic layer was
washed with brine and dried over Na SO , and concentrated to give
a crude product. The crude product was dissolved in MeOH (3 mL)
4
.1.11. (3bR,5R,9bS,11S)-5-hydroxy-7-isopropyl-6-methoxy-11-(me-
thoxymethoxy)-9b-methyl-3b,4,5,9b,10,11-hexahydrophenanthro
2,1-c]furan-1(3H)-one (17). To a solution of 16 (113 mg, 0.292 mmol)
in acetonitrile (4 mL) and water (4 mL), was added ammonium ceric
2
4
[
and a solution of NaIO
4
(19.8 mg, 0.092 mmol) in water (1 mL) was
ꢁ
ꢁ
added at 0 C. After stirring at 0 C for 50 min, the mixture was