4544
V. Kumar et al. / Tetrahedron 67 (2011) 4539e4546
which on column purification afforded the pure coupling product
13 as a white semisolid (72 mg, 72%).
IR (neat):
CD3OD)
n
¼3443, 2924, 1692, 1216, 1032 cmꢀ1; 1H NMR (300 MHz,
d
6.75 (1H, dd, J¼1.4, 5.6 Hz), 4.39 (1H, t, J¼4.3 Hz), 4.33
Eluent for column chromatography: EtOAc/hexane (3/47, v/v);
(1H, d, J¼9.9 Hz), 3.73 (1H, dd, J¼3.8, 9.9 Hz), 1.82 (3H, s); 13C NMR
D28
[
n
a
]
þ41.7 (c 0.34, CHCl3); Rf 0.55 (1/4 EtOAc/hexane); IR (KBr):
(75 MHz, CD3OD) d 200.5 (CO), 143.1 (]CH), 136.9 (qC), 75.1 (CH),
¼3022, 2924,1686,1523,1216,1091cmꢀ1;1HNMR (300 MHz, CDCl3)
73.9 (CH), 67.5 (CH), 15.7 (CH3); DART-HRMS: [MþH]ꢃþ, found
d
7.45e7.25 (15H, m), 6.58 (1H, br s); 5.09 (1H, d, J¼11.3 Hz), 4.96 (1H,
159.0640. C7H11O4 requires 159.0657.
d, J¼11.0 Hz), 4.83e4.67 (4H, m), 4.32e4.29 (1H, m), 4.03e3.89 (2H,
m), 1.82 (3H, s); 13C NMR (75 MHz, CDCl3)
d
197.6 (CO), 143.0 (]CH),
4.1.11. Compound 15. A mixture of compound 9 (207 mg, 0.5 mmol),
40% aqueous formaldehyde (0.1 mL,1 mol), 0.1 mL of THF, and DMAP
(7 mg, 0.05 mmol), was stirred for 5 days at room temperature. 1 N
HCl was then added to this reaction mixture to acidify it. It was then
extracted with ethyl acetate (3ꢂ10 mL). The combined organic layer
was washed with water (2ꢂ5 mL) and brine (2ꢂ5 mL), dried over
Na2SO4, and concentrated under reduced pressure to a residue,
which on purification using column chromatography provided
compound 15 (52 mg, 31%).
138.4 (qC),138.1 (ArqC),138.0 (ArqC),135.1 (ArqC),128.6,128.5,128.3,
128.2, 128.0, 127.98, 127.87, 127.82 (ArC), 84.8 (CH), 84.0 (CH), 78.7
(CH), 75.6 (CH2), 74.7 (CH2),þ73.6 (CH2),15.3 (CH3); Mass (ESI-MS) mþ/z
þ
428; found 446 [MþNH4]ꢃ , 429 [MþH]ꢃ ; DART-HRMS: [MþH]ꢃ
,
found 429.2069. C28H29O4 requires 429.2066.
4.1.8. Compound 14. A steel seal tube was charged with Pd2(dba)3
(9 mg, 0.0096 mmol), triphenylarsine (5.6 mg, 0.0184 mmol),
copper (I) iodide (3.4 mg, 0.018 mmol), tetramethyltin (97 mg,
0.54 mmol), iodide 12 (100 mg, 0.184 mmol), and THF (2.5 mL). The
seal tube containing the above reaction mixture was flushed with
nitrogen before the tube was sealed. The reaction mixture in the
seal tube was then heated at 80 ꢁC for 36 h. It was cooled to room
temperature and the resulting reaction mixture was diluted with
ether (50 mL), washed with 10% aqueous Na2S2O3 and 10% aqueous
potassium fluoride. The organic phase was separated, dried
(Na2SO4), and concentrated under reduced pressure to give color-
less oil, which was purified by silica gel column chromatography to
afford 14 as a white solid (54 mg, 68% yield).
Colorless semisolid, eluent for column chromatography:
EtOAc/hexane (6/19, v/v); Rf 0.40 (2/3 EtOAc/hexane); IR (KBr):
n
¼3424, 2925, 2858, 2367, 1678, 1613, 1490, 1222, 1145, 1079,
1025 cmꢀ1 1H NMR (300 MHz, CDCl3)
7.41e7.28 (10H, m), 6.62
(1H, d, J¼2.6 Hz), 6.56 (1H, d, J¼2.5 Hz), 5.63 (1H, s, OH), 5.08 (2H,
s), 5.01 (2H, s), 4.73 (2H, s); 13C NMR (75 MHz, CDCl3)
152.5
;
d
d
(ArqC), 146.5 (ArqC), 138.4 (ArqC), 137.4 (ArqC), 136.4 (ArqC), 129.1
(ArC), 128.9 (ArC), 128.8 (ArC), 128.33 (ArC), 128.27 (ArC), 128.19
(ArC), 127.9 (ArC), 126.9 (ArqC), 105.9 (ArC), 101.4 (ArC), 71.5
(CH2), 71.0 (CH2), 62.1 (CH2); DART-HRMS: [M]ꢃþ, found 336.1359.
C21H20O4 requires 336.1362.
Colorless oil, eluent for column chromatography: EtOAc/hexane
28
(3/47, v/v); [
ane); IR (neat):
a
]
ꢀ260.2 (c 0.23, CHCl3); Rf 0.56 (1/4 EtOAc/hex-
4.1.12. Compound 16. To a stirred solution of iodide 5 (0.75 g,
1.55 mmol) in THF (15 mL) was added tBuOK (0.52 g, 4.66 mmol) in
portion wise at 0 ꢁC over 2 h and allowed the reaction to stir at
room temperature for 24 h. The reaction mixture was then diluted
with ethyl acetate (15 mL) and washed with H2O (2ꢂ10 mL) and
brine (2ꢂ10 mL). The organic layer was separated, dried (Na2SO4),
and concentrated under reduced pressure to give a residue (0.6 g).
To a solution of above residue (0.6 g) in pyridine (4 mL) was
added acetic anhydride (0.3 mL, 3.3 mmol) at 0 ꢁC and allowed this
reaction mixture to warm to room temperature. After 5 h, the re-
action mixture was concentrated under reduced pressure to a res-
idue, which on column chromatography purification yielded
compound 16 (394 mg, 64%).
D
n
¼3023, 2920, 2853, 2371,1687,1217,1064 cmꢀ1; 1H
NMR (300 MHz, CDCl3)
d
7.39e7.25 (15H, m), 6.59 (1H, d, J¼3.1 Hz),
4.90 (1H, d, J¼11.5 Hz), 4.79 (2H, dd, J¼7.7, 12.2 Hz), 4.69e4.63 (3H,
m), 4.35e4.33 (2H, m), 3.95 (1H, dd, 1H, J¼3.3, 7.9 Hz), 1.80 (3H, s);
13C NMR (75 MHz, CDCl3)
d 197.4 (CO), 140.8 (]CH), 138.5 (qC and
ArqC), 138.3 (ArqC), 136.5 (ArqC), 128.83, 128.75, 128.72, 128.4,
128.2, 128.1 (ArC), 80.5 (CH), 79.0 (CH), 74.2 (CH2), 73.6 (CH2), 72.95
þ
(CH), 72.89 (CH2), 16.0 (CH3); DART-HRMS: [MþH]ꢃ
, found
429.2077. C28H29O4 requires 429.2066.
4.1.9. (þ)-4-epi-Gabosine A (1). A solution of BCl3 (0.70 mL, 1 M in
DCM) was added to a stirred solution of tribenzylated compound 13
(50 mg, 0.117 mmol) in dry DCM (5 mL) at 0 ꢁC under argon atmo-
sphere and allowed the reaction to stir at same temperature for 4 h.
After completion of reaction, methanol was added to the reaction
mixture. Evaporation of the solvent containing the reaction mixture at
reduced pressure provided a residue, which was purified using silica
gel column chromatography to a white semisolid 1 (12 mg, 64% yield).
Colorless oil, eluent for column chromatography: EtOAc/hex-
28
ane (3/47, v/v); [
hexane); IR (KBr):
a
n
]
þ26.1 (c 0.63, CHCl3); Rf 0.6 (1/4 EtOAc/
D
¼3020, 2361, 1743, 1663, 1216, 1051 cmꢀ1
;
1H
NMR (300 MHz, CDCl3)
d
7.32e7.26 (10H, m), 5.38 (1H, td, J¼2.1,
9.3 Hz), 4.89 (1H, d, J¼11.6 Hz), 4.83 (1H, d, J¼12.1 Hz), 4.71e4.64
(4H, m), 4.45 (1H, t, J¼1.7 Hz), 3.96 (1H, t, J¼9.5 Hz), 3.68 (1H,
dd, J¼3.3, 9.5 Hz), 3.43 (3H, s, OMe), 2.02 (3H, s); 13C NMR
Eluent for column chromatography: EtOAc/hexane (4/1, v/v);
28
[
a]
þ291.2 (c 0.323, MeOH); Rf 0.21 (4/1 EtOAc/MeOH); IR (KBr):
(75 MHz, CDCl3) d 170.0 (CO), 151.6 (qC), 138.8 (ArqC), 138.1
D
n
¼3447, 2923, 1690, 1218, 1073 cmꢀ1
;
1H NMR (300 MHz, CD3OD)
(ArqC), 128.9, 128.7, 128.5, 128.4, 128.1, 128.0 (ArC), 99.3 (CH),
96.5 (]CH2), 79.5 (CH), 79.3 (CH), 75.7 (CH2), 74.0 (CH2), 71.5
d
6.64 (1H, br s), 4.28 (1H, br d, J¼8.0 Hz), 3.96 (1H, d, J¼10.9 Hz),
3.52 (1H, dd, J¼8.4, 10.7 Hz), 1.80 (3H, s, CH3); 13C NMR (100 MHz,
(CH), 56.0 (CH3), 21.1 (CH3); Mass (ESI-MS) m/z 398; found 416
[MþNH4]þ
;
DART-HRMS: [MþH]þ, found 399.1796. C23H27O6
ꢃ
CD3OD)
d
200.1 (CO), 147.9 (]CH), 134.7 (qC), 80.0 (CH), 78.0 (CH),
72.5 (CH), 15.2 (CH3); DART-HRMS: [MþH]ꢃþ, found 159.0637.
requires 399.1808.
C7H11O4 requires 159.0657.
4.1.13. Compound 17. Similar synthetic procedure as adopted for
compound 16 was followed to obtain 17 from iodide 5. Yield: 60%,
colorless oil, eluent for column chromatography: EtOAc/hexane (1/
4.1.10. (ꢀ)-Gabosine A (2). A solution of BCl3 (0.76 mL, 1 M in DCM)
was added to a solution of tribenzylated compound 14 (54 mg,
0.126 mmol) in DCM at 0 ꢁC under argon atmosphere. The reaction
mixture was stirred at same temperature for 4 h. Afterward
methanol was added to the reaction mixture. The solution con-
taining the reaction mixture was evaporated at reduced pressure to
give a residue, which was purified by using silica gel column
chromatography to give 2 (13.6 mg, 68% yield).
28
9, v/v); [
a
]
ꢀ30.6 (c 0.98, CHCl3); Rf 0.6 (1/4 EtOAc/hexane); IR
D
(neat):
n
¼3021, 2363, 1746, 1663, 1218, 1053 cmꢀ1
;
1H NMR
(300 MHz, CDCl3)
d
7.33e7.26 (10H, m), 5.79 (1H, d, J¼8.6 Hz),
4.80e4.77 (2H, m), 4.72e4.68 (2H, m), 4.65e4.52 (2H, m), 4.45 (1H,
brs), 3.87e3.81 (2H, m), 3.41 (3H, s, OMe), 2.08 (3H, s); 13C NMR
(50 MHz, CDCl3) d 170.0 (CO), 153.1 (qC), 138.5 (ArqC), 138.4 (ArqC),
Colorless oil, eluent for column chromatography: EtOAc/hexane
128.8, 128.2, 128.1, 128.0, 127.9 (ArC), 101.1 (CH), 96.4 (CH2), 77.1
(CH), 75.1 (CH), 73.6 (CH2), 72.8 (CH2), 69.9 (CH), 55.9 (CH3), 21.3
28
(4/1, v/v); [
a]
ꢀ402.0 (c 0.08, MeOH); Rf 0.22 (4/1 EtOAc/MeOH);
D