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L.-A. Tziveleka et al. / Bioorg. Med. Chem. 10 (2002) 935–939
hydroxy group on the octaprenyl side chain as an
enhancing moiety. It was found that changes in the
prenyl chain result in important alterations of their
antioxidant activity. These structural requirements pro-
mote the antioxidant potency of these compounds that
may be potentially interesting antioxidant supplement
candidates.
none (10) and the aldehyde 2-[24-oxy]-octaisopentyl-1,4-
diacetoxy-benzene (8), respectively. The structures of
the derivatives were confirmed by their spectral char-
acteristics.
Derivatives 3–5 and 10 were prepared as earlier descri-
bed, and their spectral features were in accordance with
previously reported data.4 Derivatives 4, 7 and 8 are
reported for first time and their spectroscopic data are
shown below.
Experimental
Chemistry
2-[24-hydroxy]-octaprenyl-1,4-diacetoxy-benzene
(4).
Ac2O (200 mL) was added to a solution of 2 (669.4 mg,
1.0 mmol) in pyridine (5 mL) in a molar ratio of 2.1:1,
and the mixture was stirred overnight at room tem-
perature. In the resulting mixture EtOAc and H2O were
added, and the organic layer was separated, washed
with water, dried over anhydrous Na2SO4, and con-
centrated in vacuo. The residue (706.2 mg) was chro-
matographed on silica gel (cyclohexane/EtOAc) to
afford 538.7 mg of 4 (71% yield), as a colorless oil; IR
(in CHCl3): 3611, 2927, 1759, 1490, 1447, 1371, 1224,
1170, 1013 cmÀ1; UV (C6H14): lmax (e)=267 (803) nm;
1H NMR (CDCl3): d 6.89–7.02 (3H, m), 5.28 (1H, t,
J=7.3 Hz), 5.20 (1H, t, J=7.3 Hz), 5.09 (6H, m), 4.08
(2H, s), 3.20 (2H, d, J=6.9 Hz), 2.27 (3H, s), 2.26
(3H, s), 1.98–2.11 (28H, m), 1.65 (6H, s), 1.57 (18H, br);
13C NMR (CDCl3): d 169.4 (s), 169.3 (s), 148.2 (s), 146.3
(s), 138.3 (s), 137.6 (s), 135.4 (s), 135.2 (s, Â2), 134.9 (s,
Â2), 134.4 (s), 131.3 (s), 128.6 (d), 124.9 (d), 124.3 (d),
124.2 (d), 124.0 (d), 123.9 (d, Â2), 122.9 (d), 122.6 (d),
120.6 (d), 119,9 (d), 60.3 (t), 39.9 (t), 39.7 (t, Â4), 35.2 (t,
Â2), 28.5 (t), 26.9 (t), 26.7 (t, Â2), 26.6 (t, Â2), 26.5 (t),
26.2 (t), 25.7 (q), 21.1 (q), 20.8 (q), 17.7 (q), 16.2 (q,),
16.0 (q).
General details. UV spectra were determined in spectro-
scopic grade C6H14 on a Shimadzu UV model 160A. IR
spectra were obtained using a Paragon 500 Perkin-
Elmer spectrophotometer. 1H and 13C NMR spectra
were recorded using a Bruker AC 200 and DRX 400
spectrometers. Chemical shifts are given on a d (ppm)
scale using TMS as internal standard (s, singlet; d,
doublet; t, triplet; m, multiplet; br, broad). High reso-
lution FAB Mass Spectra data were recorded on a
JEOL AX505HA Mass Selective Detector and were
provided by the University of Notre Dame, Department
of Chemistry and Biochemistry, Notre Dame, Indiana.
Column chromatography was performed with Kieselgel
60 (Merk); TLCs were performed with Kieselgel 60 F254
(Merk aluminum support plates).
Sponge material. I. spinosula was collected by Scuba (2–
15 m) from Saronicos Gulf, Greece and kept frozen
until analysed. A voucher specimen is deposited at the
Herbarium of the Laboratory of Pharmacognosy
(ATPH/MO/35).
Extraction and isolation. The organism was initially
freeze dried (452.0 g) and then exhaustively extracted at
room temperature with mixtures of CH2Cl2/MeOH (3:1,
v/v). The organic extract (21.3 g) after evaporation of
the solvents was subjected to vacuum column chroma-
tography using silica gel and a step gradient system
ranging from 100% CH2Cl2 to 100% EtOAc. Metabo-
lites 1 (4.28 g) and 2 (3.36 g) were isolated as oils from
the non polar fractions, and their structural confirma-
tion was based on previously reported spectral data.4,5
2-[24-hydroxy]-octaisopentyl-1,4-diacetoxy-benzene (7).
A solution of 4 (480.6 mg, 0.64 mmol) in EtOH (10
mL) was hydrogenated using 10% Pd/C under H2
atmospheric pressure. The mixture was stirred overnight
at 50 ꢀC. Then the catalyst was removed by filtration,
and the solvent was evaporated to give 489.8 mg of pure
7 (99% yield), as a colorless oil; IR (in CHCl3): 3660,
2928, 1759, 1463, 1371, 1220, 1209, 1171 cmÀ1; UV
(C6H14): lmax (e)=267 (1046) nm; FABHRMS m/z
771.6874 [M+H]+ (calcd. for C50H90O5 770.6792); m/z
(% rel. int.) 123 (100), 165 (78), 207 (9), 263 (6), 333 (4),
403 (2), 473 (1) 557 (1), 668 (20), 686 (6), 711 (3), 728
Chemical modifications and spectral data. Hydro-
quinone derivatives were prepared by simple chemical
manipulations, such as oxidation, acetylation of the
hydroxyl groups, and hydrogenation of the chain dou-
ble bonds (Fig. 1). Polyprenylated hydroquinones 1 and
2 were treated with Ac2O in dry pyridine to afford the
corresponding acetylated products, 2-octaprenyl-1,4-
diacetoxy-benzene (3) and 2-[24-hydroxy]-octaprenyl-
1,4-diacetoxy-benzene (4). Reduction of the metabolite
1, as well as of the previously referred products 3 and 4,
with H2 using 10% Pd/C as a catalyst produced the
saturated analogues 2-octaisopentyl-1,4-hydroquinone
(5), 2-octaisopentyl-1,4-diacetoxy-benzene (6) and 2-[24-
1
(14), 753 (1); H NMR (CDCl3): d 6.89–7.02 (3H, m),
3.52 (2H, d, J=4.75), 2.44 (2H, m), 2.29 (3H, s), 2.26
(3H, s), 1.05–1.43 (52H, m), 0.86 (3H, d, J=6.5 Hz),
0.84 (18H, br), 0.81 (3H, d, J=6.5 Hz); 13C NMR
(CDCl3): d 169.4 (s), 169.3 (s), 148.2 (s), 146.2 (s),
136.2 (s), 123.0 (d, Â2), 122.8 (d, Â4), 119.7 (d, Â2),
65.7 (t), 39.3 (t), 37.4 (t, Â4), 37.3 (t), 37.2 (t), 37.1 (t),
32.8 (t, Â4), 32.7 (t, Â3), 28.0 (t), 27.8 (t), 24.8 (t, Â2),
24.5 (t, Â2), 24.4 (t), 24.3 (t), 22.7 (q), 22.6 (q), 21.1 (q),
20.9 (q), 19.7 (q, Â4), 19.6 (q), 19.5 (q).
hydroxy]-octaisopentyl-1,4-diacetoxy-benzene
(7),
2-[24-oxy]-octaisopentyl-1,4-diacetoxy-benzene (8).
A
respectively. Oxidation of 1, 2 and 7 with CrO3 in 70%
acetic acid led to the formation of quinones 2-octapre-
nyl-1,4-quinone (9), 2-[24-hydroxy]-octaprenyl-1,4-qui-
quantity of 7 (360.2 mg, 0.47 mmol), dissolved in ace-
tone (3 mL) was added to a solution of CrO3 (100 mg,
1.0 mmol) in 70% HOAc (10 mL). The resulting mix-