The Journal of Organic Chemistry
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n-hexanes, ethyl acetate) 0.27; [α]D +31.1 (c 0.28, MeOH); ECD
(MeOH; c 0.9 mg/10 mL) λ (Δε) 220 (+3.2), 240 (0), 247 (−1.8),
262 (0), 285 (+0.3) nm; UV (MeOH) λmax (log ε) 274 (0.19) nm;
νmax(film)/cm−1 2926 and 2851 (CH), 1595 and 1506 (CC), 1469,
1239, 1210, 1124 and 1010; δH (400 MHz; CDCl3; Me4Si) 1.14 (3H,
d, J = 6.8 Hz, H-9), 3.31 (2H, d, J = 6.8 Hz, H-7′), 3.85 (3H, s, OMe),
3.87 (6H, s, 2 × OMe), 3.89 (3H, s, OMe), 4.58 (1H, qd, J = 2.4, 6.8
Hz, H-8), 5.07−5.14 (3H, m, H-7 and H-9′), 5.92−6.02 (1H, m, H-
8′), 6.39 (1H, d, J = 2.0 Hz, H-6′), 6.52 (1H, d, J = 2.0 Hz, H-2′) and
6.61 (2H, s, H-2 and H-6); δC (100 MHz; CDCl3) 12.6 (C-9), 40.0
(C-7′), 56.1 (OMe), 56.2 (OMe), 60.9 (OMe), 73.2 (C-8), 77.2 (C-
7), 103.2 (C-2 and C-6), 105.1 (C-6′), 109.7 (C-2′), 115.8 (C-9′),
129.5 (C-1), 132.2 (C-4′), 132.5 (C-1′), 137.4 (C-8′), 137.7 (C-4),
143.4 (C-3′), 149.2 (C-5′) and 153.4 (C-3 and C-5); m/z (ESI+): 409
(MNa+, 100%) and 360 (67); HRMS (ESI+) Found (MNa+):
409.1610 C22H26NaO6 requires 409.1622. All NMR data was in
agreement with literature values.19
ethyl acetate) 0.36; [α]D +32.4 (c 0.80, MeOH); ECD (MeOH; c 1.1
mg/10 mL) λ (Δε) 221 (+2.0), 230 (0), 244 (−3.1), 275 (0), 283
(+0.1) nm; UV (MeOH) λmax (log ε) 271 (0.41) nm; νmax(film)/cm−1
2938 (CH), 1593 and 1497 (CC), 1475, 1253, 1127, 1088, 1007,
767 and 717; δH (400 MHz; CDCl3; Me4Si) 1.16 (3H, d, J = 6.8 Hz,
CH3), 3.85 (3H, s, OMe), 3.88 (6H, s, 2 × OMe), 3.90 (3H, s, OMe),
4.61 (1H, qd, J = 2.4, 6.8 Hz, H-3), 5.12 (1H, d, J = 2.4 Hz, H-2), 6.55
(1H, dd, J = 1.2, 8.4 Hz, H-6), 6.62 (2H, s, H-2′ and H-6′), 6.66 (1H,
dd, J = 1.2, 8.4 Hz, H-8) and 6.81 (1H, t, J = 8.4 Hz, H-7); δC (100
MHz; CDCl3) 12.6 (CH3), 56.2 (OMe), 56.2 (OMe), 60.9 (OMe),
73.3 (C-3), 77.0 (C-2), 103.2 (C-2′ and C-6′), 104.6 (C-6), 110.0 (C-
8), 120.0 (C-7), 131.5 (C-4a), 132.4 (C-1′), 137.8 (C-4′), 143.7 (C-
8a), 149.5 (C-5) and 153.4 (C-3′ and C-5′); m/z (ESI+): 369 (MNa+,
100%) and 360 (60); HRMS (ESI+) Found (MNa+): 369.1304
C19H22NaO6 requires 369.1309.
(−)-Eusiderin G, 25. To a solution of (-)-eusiderin L 23 (49.0 mg,
0.131 mmol) in dry toluene (6 mL), under an atmosphere of nitrogen
at room temperature, was added (triphenylphosphoranylidene)-
acetaldehyde (44.0 mg, 0.134 mmol). The solution was heated at
reflux for 3 days and the solvent was removed in vacuo. The crude
product was purified by flash chromatography (3:1 n-hexanes, ethyl
acetate) to yield the title product 25 (13.8 mg, 27% (95% brsm.)) as a
pale yellow oil. Rf (1:1 n-hexanes, ethyl acetate) 0.68; [α]D −19.4 (c
0.54, MeOH); ECD (MeOH; c 0.9 mg/10 mL) λ (Δε) 227 (+4.4),
257 (0), 317 (−0.7), 360 (0), 380 (+0.2) nm; νmax(film)/cm−1 2988
and 2902 (CH), 1673 (CO), 1591 and 1506 (CC), 1236, 1125,
1103, 1066 and 911; δH (400 MHz; CDCl3; Me4Si) 1.30 (3H, d, J =
6.4 Hz, H-9), 3.87 (3H, s, OMe), 3.90 (6H, s, 2 × OMe), 3.95 (3H, s,
OMe), 4.16−4.23 (1H, m, H-8), 4.58 (1H, d, J = 8.0 Hz, H-7), 6.57
(1H, dd, J = 7.6, 15.6 Hz, H-8′), 6.59 (2H, s, H-2, H-6), 6.76 (1H, d, J
= 2.0 Hz, H-6′), 6.89 (1H, d, J = 2.0 Hz, H-2′) 7.34 (1H, d, J = 15.6
Hz, H-7′) and 9.65 (1H, d, J = 7.6 Hz, C-9′); δC (100 MHz; CDCl3)
17.2 (C-9), 56.2 (OMe), 56.3 (OMe), 60.9 (OMe), 74.7 (C-8), 81.0
(C-7), 104.0 (C-6′), 104.4 (C-2 and C-6), 111.2 (C-2′), 126.5 (C-1′),
127.3 (C-8′), 131.8 (C-1), 136.1 (C-4′), 138.7 (C-4), 144.6 (C-3′),
149.1 (C-5′), 152.8 (C-7′), 153.6 (C-3 and C-5) and 193.5 (C-9′); m/
z (ESI+): 423 (MNa+, 100%), 360 (80) and 267 (15); HRMS (ESI+)
Found (MNa+): 423.1413 C22H24NaO7 requires 423.1414. The
1HNMR data was in agreement with literature values.33 (−)-Eusiderin
L 23 (35.4 mg, 0.095 mmol) was also recovered from the reaction in a
separate fraction.
(−)-Eusiderin L, 23, and (2R,3R)-3-Methyl-2-(3′,4′,5′-trime-
thoxyphenyl)-5-methoxy-1,4-benzodioxane, 22. To a stirred
solution of bromide 19a (30.0 mg, 0.07 mmol) in dry THF (1.20 mL),
under an atmosphere of nitrogen at −78 °C, was added t-BuLi (1.4 M
in THF, 0.10 mL, 0.14 mmol). After 5 min, dry DMF (0.065 mL, 0.85
mmol) was added and the mixture stirred at −78 °C for 1 h and then
allowed to warm to room temperature and left for a further 1 h. Sat.
aq. NH4Cl (3 mL) was added and the aqueous mixture extracted with
ethyl acetate (3 × 8 mL). The combined organic extracts were dried
(MgSO4) and the solvent removed in vacuo. The crude product was
purified by flash chromatography (4:1 n-hexanes, ethyl acetate) to
yield the title product 23 (19.0 mg, 73%) as a colorless oil. Rf (2:1 n-
hexanes, ethyl acetate) 0.46; [α]D −4.8 (c 1.70, MeOH); ECD
(MeOH; c 1.1 mg/10 mL) λ (Δε) 220 (+3.1), 245 (+0.6), 275 (0),
305 (−0.6), 318 (0), 332 (+0.9) nm; νmax(film)/cm−1 2939 (CH),
1686 (CO), 1590 and 1500 (CC), 1463, 1326, 1228, 1124, 1102
and 728; δH (400 MHz; CDCl3; Me4Si) 1.32 (3H, d, J = 6.4 Hz, H-9),
3.87 (3H, s, OMe), 3.90 (6H, s, 2 × OMe), 3.97 (3H, s, OMe), 4.18−
4.25 (1H, m, H-8), 4.59 (1H, d, J = 7.6 Hz, H-7), 6.59 (2H, s, H-2, H-
6), 7.12 (1H, d, J = 2.0 Hz, H-6′), 7.16 (1H, d, J = 2.0 Hz, H-2′) and
9.80 (1H, s, CHO); δC (100 MHz; CDCl3) 17.1 (C-9), 56.2 (OMe),
56.3 (OMe), 60.8 (OMe), 74.9 (C-8), 80.8 (C-7), 103.2 (C-6′), 104.5
(C-2 and C-6), 114.4 (C-2′), 129.2 (C-1′), 131.6 (C-1), 138.7 (C-4),
138.8 (C-4′), 144.4 (C-3′), 149.4 (C-5′), 153.6 (C-3 and C-5) and
190.7 (C-7′); m/z (ESI+): 397 (MNa+, 100%) and 360 (30); HRMS
(ESI+) Found (MNa+): 397.1252 C20H22NaO7 requires 397.1258.
The 1HNMR data was in agreement with literature values.19 In a
separate fraction, 22 (5.2 mg, 21%) was collected as a white solid. Rf
(2:1 n-hexanes, ethyl acetate) 0.29; mp: 138.5−142 °C; [α]D −9.2 (c
1.20, MeOH); ECD (MeOH; c 1.1 mg/10 mL) λ (Δε) 222 (+2.4),
234 (0), 238 (−0.3), 244 (0), 278 (+0.3) nm; UV (MeOH) λmax (log
ε) 272 (0.31) nm; νmax(film)/cm−1 2938 (CH), 1594 (CC), 1475,
1252, 1125, 1096, 1008 and 767; δH (400 MHz; CDCl3; Me4Si) 1.27
(3H, d, J = 6.4 Hz, CH3), 3.86 (3H, s, OMe), 3.88 (6H, s, 2 × OMe),
3.91 (3H, s, OMe), 4.11−4.15 (1H, m, H-3), 4.57 (1H, d, J = 7.6 Hz,
H-2), 6.54 (1H, dd, J = 1.2, 8.0 Hz, H-6), 6.59 (2H, s, H-2′, H-6′),
6.63 (1H, dd, J = 1.6, 8.4 Hz, H-8), 6.79 (1H, t, J = 8.0 Hz, H-7); δC
(100 MHz; CDCl3) 17.3 (CH3), 56.1 (OMe), 56.2 (OMe), 60.8
(OMe), 74.1 (C-3), 81.0 (C-2), 104.2 (C-6), 104.5 (C-2′ and C-6′),
109.9 (C-8), 120.2 (C-7), 132.4 (C-1′), 133.2 (C-4a), 138.5 (C-4′),
144.6 (C-8a), 148.8 (C-5) and 153.6 (C-3′ and C-5′); m/z (ESI+):
369 (MNa+, 100%), 360 (30) and 347 (30); HRMS (ESI+) Found
(MNa+): 369.1300 C19H22NaO6 requires 369.1309.
(−)-Eusiderin M, 5. To a solution of (−)-eusiderin G 25 (10.8 mg,
0.027 mmol) in dry methanol (2 mL), under an atmosphere of
nitrogen at room temperature was added NaBH4 (1.0 mg, 0.027
mmol) and the mixture stirred for 15 min. Water (2 mL) was added
and the mixture was extracted with ether (3 × 5 mL). The combined
organic extracts were dried (MgSO4) and the solvent removed in
vacuo. The crude product was purified by flash chromatography (2:1 n-
hexanes, ethyl acetate) to yield the title product 5 (10.5 mg, 96%) as a
colorless oil. Rf (1:1 n-hexanes, ethyl acetate) 0.37; [α]D −16.9 (c 0.77,
MeOH); ECD (MeOH; c 1.0 mg/10 mL) λ (Δε) 229 (+2.6), 241 (0),
254 (−0.9), 304 (0), 346 (+0.1) nm; νmax(film)/cm−1 3517 (OH),
2942 (CH), 1593 and 1508 (CC), 1463, 1345, 1229, 1146, 1125,
1103 and 727; δH (400 MHz; CDCl3; Me4Si) 1.27 (3H, d, J = 6.0 Hz,
H-9), 3.86 (3H, s, OMe), 3.89 (6H, s, 2 × OMe), 3.92 (3H, s, OMe),
4.10−4.16 (1H, m, H-8), 4.30 (2H, d, J = 5.6 Hz, H-9′), 4.56 (1H, d, J
= 8.0 Hz, H-7), 6.21−6.27 (1H, m, H-8′), 6.48 (1H, d, J = 15.6 Hz, H-
7′), 6.58 (2H, s, H-2, H-6), 6.60 (1H, d, J = 2.0 Hz, H-6′) and 6.68
(1H, d, J = 2.0 Hz, H-2′); δC (100 MHz; CDCl3) 17.3 (C-9), 56.2
(OMe), 56.2 (OMe), 60.8 (OMe), 63.7 (C-9′), 74.3 (C-8), 81.1 (C-
7), 102.4 (C-6′), 104.5 (C-2 and C-6), 108.2 (C-2′), 127.2 (C-8′),
129.3 (C-1′), 131.0 (C-7′), 132.3 (C-4′), 133.0 (C-1), 138.6 (C-4),
144.4 (C-3′), 148.8 (C-5′) and 153.6 (C-3 and C-5); m/z (ESI+): 425
(MNa+, 100%), 399 (40), 360 (40) and 264 (30); HRMS (ESI+)
Found (MNa+): 425.1584 C22H26NaO7 requires 425.1571. The
1HNMR data was in agreement with literature values except for the
(2S,3R)-3-Methyl-2-(3′,4′,5′-trimethoxyphenyl)-5-methoxy-
1,4-benzodioxane, 24. To a solution of bromide 19b (23.0 mg,
0.054 mmol) in dry THF (1.00 mL) under an atmosphere of nitrogen
at −78 °C was added t-BuLi (1.4 M in THF, 0.10 mL, 0.14 mmol) and
the mixture stirred for 10 min. Sat. aq. NH4Cl (3 mL) was added and
the aqueous mixture extracted with ethyl acetate (3 × 8 mL). The
combined organic extracts were dried (MgSO4) and the solvent
removed in vacuo. The crude product was purified by flash
chromatography (4:1 n-hexanes, ethyl acetate) to yield the title
product 24 (15.1 mg, 81%) as a pale yellow oil. Rf (2:1 n-hexanes,
assignment of two protons which should be interchanged.19
(1R,2R)-2-(2′-(Benzyloxy)-4′-bromo-6′-methoxyphenoxy)-1-
(3″,4″-methylenedioxyphenyl)propan-1-ol, 26a and (1S,2R)-2-
(2′-(Benzyloxy)-4′-bromo-6′-methoxyphenoxy)-1-(3″,4″-
I
dx.doi.org/10.1021/jo3015006 | J. Org. Chem. XXXX, XXX, XXX−XXX