Notes
J ournal of Natural Products, 2002, Vol. 65, No. 5 727
(OCH3), 102.8 (C-1), 106.2 (C-5), 117.6 (C-4), 137.4 (C-2), 142.7
(C-3), 156.8 (C-6), 173.9 (CO2H); EIMS m/z (%) 183 (7), 165
(9), 150 (16), 139 (63), 124 (100), 122 (3), 110 (3), 109 (7), 96
(24), 95 (4), 80 (3), 68 (5), 44 (28); HREIMS m/z 183.0534 (M+,
calcd 183.0532 for C8H9NO4).
(3.20), 424 (sh, 2.57). 604 (2.25) nm; 1H NMR (CD3OD, 600
MHz) δ 3.76 (3H, s, OCH3), 4.09 (2H, s, PhCH2N), 5.12 (2H, s,
PhCH2O), 6.91 (1H, s, 6-H), 7.20-7.49 (10H, m, Ph), 7.27 (1H,
s, 6′-H); 13C NMR (151 MHz, CD3OD) δ 44.4 (PhCH2N), 56.6
(OCH3), 68.0 (PhCH2O), 94.7 (C-3′), 103.0 (C-3), 106.4 (C-1),
117.4 (C-6), 126.9 (C-6′), 128.5, 128.8, 129.1, 129.4, 129.8,
130.2, 132.3, 134.7 (each Ph), 140.4 (C-5), 146.9 (C-1′), 148.3
(C-4), 156.6 (C-4′), 161.7 (C-2), 168.9 (C-7 or C-7′), 175.1 (C-7
or C-7′), 177.2 (C-5′), 186.0 (C-2′).
Ca ta lytic Hyd r ogen a tion of 7. Blennione (1) was obtained
from 1.1 mg of 7 in 5 mL of MeOH in a small autoclave
containing 0.5 mg of PtO2 × H2O and a Teflon stirring bar.
After 12 h stirring at 20 °C under 10 atm pressure of H2, the
solution was passed through a fiberglass filter. During this
procedure the solution turned green again. The solvent was
removed in vacuo and the residue purified on a Sephadex LH-
20 column (25 × 1 cm, eluent MeOH) to yield 1 (0.44 mg,
60%): UV/vis (MeOH) λmax 222, 255, 342, 434, 678 nm; 1H
NMR (600 MHz, CD3OD) δ 3.81 (3H, s, OCH3), 7.07 (1H, s),
7.25 (1H, s), identical to natural 1.
Ben zyl 2,5-Dih yd r oxyben zoa te (5). To 2,5-dihydroxy-
benzoic acid (5.00 g, 32.4 mmol) in acetone (200 mL) was slowly
added K2CO3 (4.93 g, 35.7 mmol) and benzyl chloride (4.32 g,
35.7 mmol) in acetone (20 mL).14 After 12 h of stirring at 70
°C, the suspension was cooled to 20 °C and filtered. The solvent
was evaporated in vacuo at 40 °C, and the residue was
dissolved in EtOAc (10 mL) and filtered through a 5 cm layer
of silica gel to give pure benzyl 2,5-dihydroxybenzoate (7.77
g, 98%) as colorless crystals, mp 91 °C: 1H NMR (600 MHz,
3
CDCl3) δ 5.36 (2H, s, PhCH2O), 6.88 (1H, d, J HH ) 8.9 Hz,
3
4
3-H), 6.99 (1H, dd, J HH ) 8.9 Hz, J HH ) 2.8 Hz, 4-H), 7.32
(1H, d, 4J HH ) 2.8 Hz, 6-H), 7.36-7.44 (5H, m, Ph), 10.34 (1H,
s, 2-OH); 13C NMR (151 MHz, CDCl3) δ 67.8 (PhCH2O), 112.9
(C-1), 115.5 (C-6), 119.2 (C-3), 124.9 (C-4), 129.0 (C-2′, C-6′),
129.3 (C-4′), 129.4 (C-3′, C-5′), 135.9 (C-1′), 148.4 (C-5), 156.7
(C-2), 170.2 (PhCH2OCO); EIMS m/z (%) 244 (38), 153 (1), 137
(3), 136 (3), 109 (1), 108 (2), 91 (100), 65 (7), 43 (3); HREIMS
m/z 244.0738 (M+, calcd 244.0736 for C14H12O4).
Ack n ow led gm en t. We thank the Deutsche Forschungs-
gemeinschaft (SFB 369) and the Fonds der Chemischen
Industrie for generous support and Prof. Michael Spiteller,
Dortmund, for the APCIMS measurements.
3-Ben zyla m in o-2-ben zyloxyca r bon yl-1,4-ben zoqu in o-
n e (6). To a solution of benzyl 2,5-dihydroxybenzoate (7.70 g,
31.5 mmol) in CH2Cl2 (100 mL) was added activated MnO2
(5.00 g). After stirring for 24 h at 20 °C, the solid was filtered
off and the solvent removed in vacuo. The residue was
dissolved in 1 mL of EtOAc/hexanes (1:4) and chromato-
graphed on a silica gel column (20 × 3 cm) with the same
solvent mixture. 2-Benzyloxycarbonyl-1,4-benzoquinone (2.90
g, 38%) was obtained as an air-sensitive orange solid: 1H NMR
(600 MHz, CDCl3) δ 5.36 (2H, s, PhCH2O), 6.71 (2H, m, 3-H,
4-H), 7.08 (1H, s, 6-H), 7.36-7.49 (5H, m, Ph); EIMS m/z 244
(6) [M + 2 H]+, 242 (0.3), 91 (100), 65 (9).
To a solution of this quinone (100 mg, 0.42 mmol) in EtOAc
(500 mL) was added activated MnO2 (100 mg). The mixture
was vigorously stirred under argon and treated dropwise with
a solution of benzylamine (45 µL, 0.41 mmol) in 25 mL of
EtOAc (6 drops/min). This operation required 3 h. After 2 h of
further stirring, the mixture was passed through a fiberglass
filter and concentrated in vacuo at 20 °C to 10 mL. Since 6
could not be purified or isolated without decomposition, the
crude solution was used for the next reaction step.
2-Am in o-5-(4-N-b en zyla m in o-5-ca r b oxyb en zyl-3,6-d i-
oxocycloh exa -1,4-d ien yl)-6-h yd r oxy-3-m et h oxyb en zoic
Acid (7). To a solution of 3 (13 mg, 70 µmol) in MeOH (50
mL) was added silica gel (100 mg), and the mixture was placed
in a two-necked 250 mL round-bottom flask and kept under
argon. To the vigorously stirred mixture was added dropwise
crude 6 in EtOAc (10 mL, see above) at 25 °C. The color of the
solution turned greenish brown immediately. After 1 h of
stirring, the silica gel was filtered off and the solvent removed
in vacuo at 30 °C. The brown residue was dissolved in MeOH
(0.5 mL) and chromatographed on a RP-18 HPLC column with
UV detection at λ ) 280 nm (tR ∼30 min) to yield 7 (1.1 mg,
3%): UV/vis (MeOH) λmax (log ꢀ) 214 (3.49), 240 (sh, 3.38), 344
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