2814
T. Ogura, T. Usuki / Tetrahedron 69 (2013) 2807e2815
0.204 mmol, 69%) as a colorless solid; Rf 0.50 (hexane/EtOAc¼3:1);
mp 75e76 ꢁC; IR (neat, cmꢀ1) 2932, 1646, 1604, 1507, 1247, 1173,
t, J¼7.3 Hz, H7), 2.36 (2H, t, J¼6.4 Hz, H4), 1.62 (2H, m, H6), 1.57 (2H,
m, H5); 13C NMR (125 MHz, pyridine-d5) 209.6 (C3), 157.3 (C40 or
d
1035, 981, 818; 1H NMR (300 MHz, CDCl3)
d
7.53e7.43 (3H, m, H5/7/
C400), 157.1 (C40 or C400), 133.1 (C10 or C100), 132.2 (C10 or C100), 130.0
(C20/60/200/600), 116.2 (C30/50/300/500), 44.8 (C2), 42.8 (C4), 35.2 (C7),
31.7 (C5), 29.5 (C1), 23.7 (C6); EI-HRMS (m/z) calcd for C19H22O3
[M]þ 298.1569, found 298.1588.
19), 7.10 (2H, d, J¼8.5 Hz, H15/18), 6.91 (2H, d, J¼8.6 Hz, H2/4), 6.82
(2H, d, J¼8.5 Hz, H1/16), 6.61 (1H, d, J¼16.2 Hz, H8), 3.84 (3H, s,
OMe), 3.78 (3H, s, OMe), 2.69e2.54 (4H, m, H10/13), 1.80e1.58 (4H,
m, H11/12); 13C NMR (CDCl3, 75 MHz)
d 200.6, 161.7, 142.3, 134.5,
130.1, 129.4, 127.4, 124.2, 114.5, 113.9, 55.5, 55.4, 40.8, 35.0, 31.5,
24.2; EI-HRMS (m/z) calcd for C21H24O3 [M]þ 324.1725, found
324.1718.
4.17. Centrolobol (4)12
To a solution of acerogenin G (3, 30.3 mg, 0.102 mmol) in MeOH
cooled to
0
ꢁC was added sodium borohydride (35.1 mg,
4.14. 1,7-Bis-(4-methoxyphenyl)-heptan-3-one (24)
0.928 mmol). After being stirred at room temperature for 20 min,
the reaction mixture was diluted with water and extracted with
EtOAc. The combined organic layers were washed with brine, dried
over Na2SO4, and concentrated in vacuo. Purification by silica gel
column chromatography (hexane/EtOAc¼1:1) afforded 4 (29.7 mg,
A mixture of 31 (185 mg, 0.570 mmol) and 10% Pd/C (74.0 mg) in
CHCl3 (3 mL) was stirred under H2 atmosphere using a balloon at
room temperature for 10 h. The reaction mixture was filtered
through a pad of Celite and washed with CHCl3. The filtrate was
then concentrated in vacuo. Purification by silica gel column
chromatography (hexane/EtOAc¼5:1) afforded 24 (154 mg,
0.472 mmol, 83%) as a colorless solid; Rf 0.60 (hexane/EtOAc¼3:1);
98.9
m
mol, 97%) as a colorless powder; Rf 0.31 (hexane/EtOAc¼1:1);
25
mp 116e119 ꢁC; [
a
]
ꢀ1.1 (c 0.9, MeOH); IR (neat, cmꢀ1) 3566,
D
3483, 1642, 1596, 1495, 1245, 1166, 1030; 1H NMR (500 MHz, ace-
tone-d6)
d
8.04 (2H, br s, ArOH), 7.06e6.97 (4H, m, H20/60/200/600),
1H NMR (300 MHz, CDCl3)
d
7.13e7.02 (4H, m, H5/15/18/19), 6.81
6.73 (4H, d, J¼8.3 Hz, H30/50/300/500), 3.54 (1H, m, H3), 3.48 (1H, m,
OH), 2.69 (1H, m, H1a), 2.60e2.45(3H, m, H1b/7), 1.78e1.26 (8H, m,
(4H, d, J¼8.6 Hz, H1/2/4/16), 3.78 (6H, s, OMe), 2.83 (2H, t, J¼7.5 Hz,
H7), 2.67 (2H, t, J¼7.6 Hz, H8), 2.54 (2H, t, J¼7.1 Hz, H13), 2.38 (2H, t,
J¼6.9 Hz, H10), 1.66e1.47 (4H, m, H11/12); 13C NMR (CDCl3,
H2/4/5/6); 13C NMR (125 MHz, acetone-d6) 156.14 (C40/400), 134.25
d
(C10 or C100), 134.20 (C10 or C100), 130.04 (C20/60 or C200/600), 130.01
(C20/60 or C200/600), 115.87 (C30/50 or C300/500), 115.83 (C30/50 or C300/
500), 70.81 (C3), 40.74 (C2), 38.32 (C4), 35.68 (C7), 32.80 (C6), 31.87
(C1), 26.09 (C5); EI-HRMS (m/z) calcd for C19H24O3 [M]þ 300.1725,
found 300.1714.
75 MHz)
d 210.4, 158.1, 134.4, 133.3, 129.4, 113.9, 55.4, 44.7, 43.0,
34.9, 31.3, 29.1, 23.5; EIMS (m/z) calcd for C21H26O3 [M]þ 326.19,
found 326.20.
4.15. 1,7-Bis-(3-iodo-4-methoxyphenyl)-heptan-3-one (23)
4.18. 3,17-Dimethoxy-tricyclo[12.3.1.12,6]nonadeca-
1(17),2(19),3,5,14(18),15-hexaen-9-one (5)
To a solution of 1,7-bis-(4-methoxyphenyl)-heptan-3-one (24,
277.6 mg, 0.850 mmol) in CHCl3 (8 mL) was added silver tri-
fluoroacetate (750 mg, 3.40 mmol). To the stirred suspension was
added a solution of iodine (863 mg, 3.40 mmol) in CHCl3 (20 mL)
dropwise over 15 min. The suspension was stirred at room tem-
perature for 30 min and then filtered through a pad of Celite. To the
filtrate was added saturated Na2SO3 solution until the reaction
mixture turned to colorless. The aqueous layer was extracted with
CH2Cl2, and the combined organic layers were dried over Na2SO4,
and concentrated in vacuo. Twice of purification by silica gel col-
umn chromatography (hexane/EtOAc¼8:1) afforded 23 (372 mg,
To a mixture of 1,7-bis-(3-iodo-4-methoxyphenyl)-heptan-3-
one (23, 59.8 mg, 0.103 mmol), PdCl2(dppf) (7.6 mg, 10
mmol),
bis(pinacolato)diboron (32.0 mg, 0.126 mmol) and AcOK (102 mg,
1.04 mmol) was added degassed DMSO (10.3 mL). The reaction
mixture was stirred at 100 ꢁC for 24 h. After cooling to 0 ꢁC, satu-
rated NH4Cl solution was added and extracted with EtOAc. The
combined organic layer was dried over Na2SO4 and concentrated in
vacuo. Purification by silica gel short column chromatography
(hexane/EtOAc¼1:1) and silica gel column chromatography (hex-
0.644 mmol, 76%) as
a
colorless powder; Rf 0.43 (hexane/
ane/EtOAc¼5:1) afforded 5 (11.4 mg, 35.1
mmol, 34%) as a colorless
EtOAc¼3:1); mp 57e58 ꢁC; IR (neat, cmꢀ1) 2930, 1705, 1600, 1488,
powder; Rf 0.41 (hexane/EtOAc¼3:1); mp 147e148 ꢁC; IR (neat,
1252,1050, 805; 1H NMR (300 MHz, CDCl3)
d
7.61e7.54 (2H, m, H18/
cmꢀ1) 2933, 1699, 1505, 1461, 1260, 1032, 816; 1H NMR (300 MHz,
19), 7.14e7.04 (2H, m, H5/15), 6.78e6.66 (2H, m, H4/16), 3.85 (3H, s,
OMe), 3.84 (3H, s, OMe), 2.79 (2H, t, J¼7.0 Hz, H7), 2.66 (2H, t,
J¼6.9 Hz, H8), 2.50 (2H, t, J¼7.2 Hz, H13), 2.38 (2H, t, J¼6.6 Hz, H10),
pyridine-d5) d 7.16e7.06 (2H, m, H5/15), 7.00e6.82 (4H, m, H4/16/
18/19), 3.77 (3H, s, OMe), 3.75 (3H, s, OMe), 3.38e2.34 (8H, m, H7/8/
10/13), 1.90e1.56 (4H, m, H11/12); 13C NMR (75 MHz, pyridine-d5)
1.64e1.44 (4H, m, H11/12); 13C NMR (CDCl3, 75 MHz)
d
209.8, 156.7,
d 213.1, 156.2, 155.7, 135.0, 133.0, 131.7, 130.2, 129.6, 129.4, 128.6,
139.3, 139.2, 136.6, 135.5, 129.6, 129.5, 111.0, 110.9, 86.1, 86.0, 56.5,
44.4, 42.9, 34.4, 31.1, 28.4, 23.3; EI-HRMS (m/z) calcd for C21H24I2O3
[M]þ 577.9815, found 577.9823.
112.1, 111.9, 55.9, 46.5, 42.6, 32.0, 29.6, 25.9, 21.5; EI-HRMS (m/z)
calcd for C21H24O3 [M]þ 324.1725, found 324.1718.
4.19. Acerogenin E (1)1h
4.16. Acerogenin G (3)1f
To a solution of 3,17-dimethoxy-tricyclo[12.3.1.12,6]nonadeca-
To a solution of 1,7-bis-(4-methoxyphenyl)-heptan-3-one (24,
95.6 mg, 0.293 mmol) in CH2Cl2 (5 mL) cooled to ꢀ78 ꢁC was
dropwisely added BBr3 (1 M in CH2Cl2, 1.46 mL, 1.46 mmol). The
temperature was gradually raised to 0 ꢁC. After stirring for 4 h,
saturated NaHCO3 solution was added at 0 ꢁC. The aqueous layer
was extracted with EtOAc, dried over Na2SO4, and then concen-
trated in vacuo. Purification by silica gel column chromatography
1(17),2(19),3,5,14(18),15-hexaen-9-one (5, 13.3 mg, 41.0 mmol) in
CH2Cl2 (1.5 mL) cooled to ꢀ78 ꢁC was added BBr3 (1 M in CH2Cl2,
205 mL, 0.205 mmol). The temperature was allowed to gradually
rise to 0 ꢁC. After stirring for 3 h, saturated NaHCO3 solution was
added at 0 ꢁC. The aqueous layer was extracted with EtOAc, dried
over Na2SO4, and then concentrated in vacuo. Purification by silica
gel column chromatography (hexane/EtOAc¼2:1) afforded
1
(hexane/EtOAc¼2:1) afforded 3 (71.9 mg, 0.241 mmol, 82%) as
(11.4 mg, 38.5 mmol, 94%) as a colorless powder; Rf 0.54 (hexane/
25
25
a colorless amorphous; Rf 0.46 (hexane/EtOAc¼1:1); [
a]
ꢀ0.1 (c
EtOAc¼1:1); mp 230e232 ꢁC; [
a
]
ꢀ0.3 (c 0.8, MeOH); IR (neat,
D
D
0.8, MeOH); IR (neat, cmꢀ1) 3600, 3097, 1644, 1494, 1248, 1047; 1H
cmꢀ1) 3280, 2939, 1694, 1507, 1403, 1243, 819; 1H NMR (500 MHz,
NMR (500 MHz, pyridine-d5)
d
7.24e7.02 (8H, m, H20/30/50/60/200/300/
pyridine-d5)
d 7.26e7.05 (6H, m, H4/5/15/16/18/19), 4.99 (2H, br s,
500/600), 2.94 (2H, t, J¼7.5 Hz, H1), 2.71 (2H, t, J¼7.5 Hz, H2), 2.53 (2H,
ArOH), 3.08 (2H, m, H7), 2.80 (2H, t, J¼5.1 Hz, H8), 2.75e2.61 (4H,