Short and efficient synthesis of (+)-subersic acids

Article abstract of DOI:10.1016/j.tet.2003.09.048

An efficient synthesis of (+)-subersic acid, the unnatural enantiomer, has been achieved from sclareol and p-hydroxybenzoic acid.

Full text of DOI:10.1016/j.tet.2003.09.048

Tetrahedron 59 (2003) 9173–9177
Short and efficient synthesis of (1)-subersic acids
*
Pilar Basabe, Alberto Diego, Sergio Delgado, David Dıez, Isidro S. Marcos and Julio G. Urones
´
´ ´ ´ ´
Departamento de Quımica Organica, Facultad de Ciencias Quımicas, Universidad de Salamanca, Plaza de los Caıdos 1-5,
37008 Salamanca, Spain
Received 27 June 2003; revised 2 September 2003; accepted 16 September 2003
Abstract—An efficient synthesis of (þ)-subersic acid, the unnatural enantiomer, has been achieved from sclareol and p-hydroxybenzoic
acid.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
synthesis (Scheme 1) was the coupling of the diterpene part
with the lithiated arene unit.
(2)-Subersic acid was isolated from the sponge Suberea sp.
by Crews and co-worker.1 The natural product was an
inhibitor of human 15-lipoxygenase, assay that has been
employed to discover new marine-sponge derived bioactive
compounds. The availability of inhibitors could provide
biomolecules that are useful as pharmacological agents.
The synthesis of the aromatic fragment 6 is summarized in
Scheme 2. The starting methyl 4-hydroxybenzoate 2 by
treatment with Br23 gives the bromo derivated 3. Protection
of the 3 as methoxymethyl ether4 and subsequent DIBAL
reduction5 of 4, gives alcohol 5 in excellent yield. The
alcohol 5 was transformed6 in the THP derivative 6.
Recently Mori and co-workers2 reported the synthesis and
absolute configuration of (2)-subersic acid. The acid 1 was
synthesized from (S)-3-hydroxy-2,2-dimethylcyclohexa-
none and p-hydroxybenzoic acid. The stereochemistry was
established as (5R,10R).
The diterpene fragment 11 necessary for the final coupling
was obtained from sclareol according to Scheme 3. Sclareol
was acetylated in quantitative yield with acetyl chloride and
N,N-dimethylaniline, affording the diacetyl derivative 7
whose isomerization with bis-(acetonitrile)palladium (II)
chloride7,8 led to diacetate 8 (92%).
Treatment of 8 with HI in benzene9 gives the monoacetate 9.
The hydrolysis of the acetoxy group of 9 and subsequent
10,11
halogenation with CBr4/PPh3
11.
gave the allylic bromide
Scheme 4 shows the final stage of the synthesis to give (þ)-
subersic acid. The lithiated arene unit was generated from
the bromo derivative 6 by treatment with t-BuLi. It was then
alkylated with the bromide 11 to give the coupling product
that was transformed to 12 by removing the THP protective
group.
Oxidation of 12 with MnO2 gives the aldehyde 13 in
excellent yield. Treatment of 13 with sodium chlorite12 and
removing of protective group furnished (þ)-subersic acid,
[a]2D0¼þ49 (c¼0.78, CHCl3), (2)-subersic acid,1
[a]2D0¼246 (c¼0.5, CHCl3)
2. Results and discussion
In this work we report the synthesis of (þ)-subersic acid
from naturally occurring (2)-sclareol. The key step of the
The efficiency of this synthesis allows the availability of the
target molecule for activity test as human 15-lipoxygenase
inhibitor, that is currently in progress.
Keywords: (þ) subersic acid; meroterpenes; sclareol.
*
Corresponding author. Tel.: þ34-923294474; fax: þ34-923294574;
e-mail: pbb@usal.es
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.09.048

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P. Basabe et al. / Tetrahedron 59 (2003) 9173–9177
Scheme 1.
Scheme 2. (a) Br2, DCM, rt, 24 h, 95%; (b) DMM, P2O5, CHCl3, rt, 10 min, 99%; (c) DIBAL-H, DCM, 2788C, 1 h, 99%; (d) DHP, HCl/dioxane 4 M, rt,
10 min, 99%.
Scheme 3. (a) AcCl, N,N-dimethylaniline, DCM, rt, 24 h, 97%; (b) PdCl2(MeCN)2, THF, rt, 4 h, 92%; (c) HI, C6H6, rt, 11 h, 48%; (d) K2CO3/MeOH 3%, rt,
98%; (e) CBr4, PPh3, DCM, 08C, 10 min, 99%.

P. Basabe et al. / Tetrahedron 59 (2003) 9173–9177
9175
Scheme 4. (a) 6, tBuLi, THF, 2788C!rt, 3 h; (b) pTsOH, MeOH, rt, 1 h, 26% (from 11); (c) MnO2, DCM, rt, 3 h, 85%; (d) NaClO2, tBuOH, rt, 2 h; (e) HCl
6 M, THF, 458C, 3 h, 47% (from 13).
3. Experimental
J¼8.4 Hz, H-5), 3.89 (3H, s, COOMe); 13C NMR d: 166.0
(COOMe), 156.6 (C-4), 134.3 (C-2), 131.2 (C-6), 124.1
(C-1), 116.1 (C-5), 110.3 (C-3), 52.5 (COOMe); EIMS m/z:
232, 230 (M)þ (34, 34), 201 (80), 199 (81), 171 (6), 152
(42), 121 (100), 93 (22), 69 (26); HREIMS: calcd for
C8H7O3Br (M)þ: 229.9578, found: 229.9580.
3.1. General
Unless otherwise stated, all chemicals were purchased as the
highest purity commercially available and were used
without further purification. Melting points were deter-
mined with a Kofler hot stage melting point apparatus and
are uncorrected. IR spectra were recorded on a BOMEM
3.1.2. 3-Bromo-4-methoxymethoxybenzoic acid methyl
ester (4). To an ice cooled solution of 3 (1.71 g, 7.4 mmol)
in dry CHCl3 (50 mL) and dimethoxymethane (50 mL) was
added P2O5 (10 g, 70.4 mmol). The reaction was stirred for
10 min at rt and then, the mixture was poured into ice and
the aqueous layer extracted with Et2O. The organic layer
were collected and washed with aq. solution of NaHCO3
10% and water, dried over Na2SO4 and concentrated to
afford 4 (2.03 g, 99%) as a pale yelow solid. Mp: 568C
(hexane–Et2O); IR (film): 1723, 1599, 1495, 1435, 1289,
1
100 FT IR spectrophotometer. H and 13C NMR spectra
were performed in deuterochloroform and referenced to the
residual peak of CHCl3 at d 7.26 ppm and d 77.0 ppm for 1H
and 13C, respectively, using a Bruker WP-200 SY and a
BRUKER DRX 400 MHz. Chemical shifts are reported in d
ppm and coupling constants (J) are given in Hz. MS were
performed in a VG-TS 250 spectrometer at 70 eV ionizing
voltage. Mass Spectra are presented as m/z (% rel. int.).
HRMS were recorded in a VG Platform spectrometer
using Electronic Impact (EI) or Fast Atom Bombardment
(FAB) technique. Optical rotations were determined in a
Perkin–Elmer 241 polarimeter in 1 dm cells. Diethyl
ether, THF and benzene were distilled from sodium, and
pyridine and dichloromethane were distilled under argon
from CaH2.
1
1258, 1161, 1115, 1044, 980, 766 cm21; H NMR d: 8.24
(1H, d, J¼2.2 Hz, H-2), 7.94 (1H, dd, J¼2.2, 8.4 Hz, H-6),
7.16 (1H, d, J¼8.4 Hz, H-5), 5.31 (2H, s, OCH2O), 3.89
(1H, s, COOMe), 3.52 (3H, s, OCH3); 13C NMR d: 165.9
(COOMe), 157.6 (C-4), 135.1 (C-2), 130.6 (C-6), 125.0
(C-1), 114.9 (C-5), 112.6 (C-3), 95.0 (OCH2O), 56.8
(OCH3), 52.4 (COOMe); EIMS m/z 276, 274 (M)þ (44,
56), 245 (22), 196 (58), 125 (848), 107 (30), 77 (75), 63
(100); HREIMS: calcd for C10H11O4Br (M)þ: 273.9841,
found: 273.9817.
3.1.1. 3-Bromo-4-hydroxybenzoic acid methyl ester (3).
To a solution of 2 (1.19 g, 7.8 mmol) in dry DCM (90 mL)
was added bromine (0.4 mL, 78.8 mmol) at 258C dropwise.
The mixture was stirred at rt for 24 h. After this time an aq.
solution of Na2S2O3 10% was added and the aqueous layer
extracted with DCM, dried over Na2SO4 and evaporated to
give 3 (1.71 g, 95%) as pale yellow solid. Mp: 1058C
(hexane–Et2O); IR (KBr): 3351, 1690, 1508, 1292, 1265,
3.1.3. (3-Bromo-4-methoxymethoxyphenyl)methanol (5).
To a solution of 4 (210 mg, 0.8 mmol) in dry DCM (14 mL)
under argon, was added a solution of DIBAL-H in toluene
(1.5 M, 1.3 mL, 1.9 mmol) at 2788C. The solution was
stirred for 1 h and was quenched by addition of MeOH and
water. A saturated solution of tartrate Naþ and Kþ was
added, the mixture was stirred for an additional hour and the
1
1044, 970, 764 cm21; H NMR d: 8.19 (1H, d, J¼2.2 Hz,
H-2), 7.92 (1H, dd, J¼2.2, 8.4 Hz, H-6), 7.05 (1H, d,

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P. Basabe et al. / Tetrahedron 59 (2003) 9173–9177
aqueous layer was extrated with AcOEt. The collected
organic layer were washed with an aq. solution of NaHCO3
10% and water, dried over Na2SO4, concentrated under
reduced pressure to give 5 (188 mg, 99%) as a pale brown
oil. IR (film): 3380, 1605, 1495, 1404, 1244, 1202, 1159,
3.1.6. 15-Hydroxy-13E,8(9)-labdadiene (10). A solution
of K2CO3 in methanol (3%, 56 mL) was added to 9 (1.86 g,
5.6 mmol) and the reaction was stirred vigorously at rt for
4 h until no starting material remained. Then water was
added and the mixture was concentrated to remove the
methanol and the aqueos layer was extracted with Et2O. The
organic layer was washed with water, dried over Na2SO4
and evaporated to provide 10 (1.59 g, 98%) as a colourless
oil. [a]2D0¼þ62 (c¼0.46, CHCl3); IR (film): 3352, 1669,
1086, 1044, 924, 816 cm21 1H NMR d: 7.56 (1H, d,
;
J¼1.8 Hz, H-2), 7.23 (1H, dd, J¼1.8, 8.4 Hz, H-6), 7.11
(1H, d, J¼8.4 Hz, H-5), 5.23 (2H, s, OCH2O), 4.60 (2H, s,
H-7), 3.51 (3H, s, OCH3); 13C NMR d: 153.4 (C-4), 136.2
(C-1), 132.3 (C-2), 127.4 (C-6), 116.4 (C-5), 113.1 (C-3),
95.4 (OCH2O), 64.4 (C-7), 56.6 (OCH3); EIMS m/z: 248,
246 (M)þ (96, 100), 218 (36), 186 (18), 167 (14), 137 (15),
108 (19), 94 (27), 65 (55); HREIMS: calcd for C9H11O3Br
(M)þ: 245.9892, found: 245.9878.
1
1458, 1443, 1375, 1003 cm21; H NMR d: 5.42 (1H, t,
J¼6.9 Hz, H-14), 4.15 (2H, d, J¼6.9 Hz, H-15), 2.15–1.90
(6H, m, H-12, H-11 and H-7), 1.85–1.78 (1H, m, Ha-1) 1.70
(3H, s, Me-16), 1.70–1.37 (5H, m, H-2, H-6 and Ha-3), 1.57
(3H, s, Me-17), 1.20–1.10 (3H, m, Hb-3, Ha-1 and H-5),
0.94 (3H, s, Me-20), 0.88 (3H, s, Me-18), 0.83 (3H, s, Me-
19); 13C NMR d: 140.6 (C-13), 140.1 (C-9), 126.0 (C-8),
122.6 (C-14), 59.3 (C-15), 51.9 (C-5), 41.8 (C-3), 40.1
(C-12), 39.0 (C-10), 37.0 (C-1), 33.6 (C-7), 33.3 (C-4 and
C-18), 26.7 (C-11), 21.7 (C-19), 20.1 (C-20), 19.4 (C 17),
19.0 (C-6 and C-2), 16.3 (C-16); EIMS m/z: 290 (M)þ(7),
245 (5), 205 (100), 149 (48), 109 (93), 69 (82); HREIMS:
calcd for C20H34O (M)þ: 290.2610, found: 290.2599.
3.1.4. Tetrahydropyranyloxy derivative of (3-bromo-4-
methoxymethoxyphenyl)methanol (6). To a solution of
DHP (527 mg, 6.3 mmol) in dry DCM (1 mL) was added a
solution of HCl in dioxane (4 M, 30 mL, 0.12 mmol) and
1 min later 5 (664 mg, 2.69 mmol) was added diluted in
DCM (20 mL). The reaction was stirred vigorously for
10 min and then an aq. solution of NaHCO3 10% was added
and the aqueous layer was extracted with AcOEt. The
organic layer was washed with an aq. solution of NaHCO3
10% and water, dried over Na2SO4 and evaporated to afford
an oily residue. The purification by Florisilw chromato-
graphy with hexane–AcOEt (95:5) as eluent gave 6
(887 mg, 99%) as a colourless oil. IR (film): 1497, 1244,
1202, 1159, 1121, 1082, 1044, 991, 907, 870, 816 cm21; 1H
NMR d: 7.56 (1H, d, J¼2.2 Hz, H-2), 7.23 (1H, dd, J¼2.2,
8.4 Hz, H-6), 7.11 (1H, d, J¼8.4 Hz, H-5), 5.24 (2H, s,
OCH2O), 4.69 (1H, d, J¼12.2 Hz, Ha-7), 4.68 (1H, t,
J¼3.2 Hz, H-20), 4.40 (1H, d, J¼12.2 Hz, Hb-7), 3.90–3.40
(2H, m), 3.51 (3H, s, OCH3), 1.90–1.45 (6H, m); 13C NMR
d: 153.4 (C-4), 133.6 (C-1), 133.2 (C-2), 128.3 (C-6), 116.2
(C-5), 113.0 (C-3), 97.9 (C-20), 95.4 (OCH2O), 67.9 (C-7),
62.40 (C-60), 56.6 (OCH3), 30.7 (C-30), 25.6 (C-50), 19.5
(C-4 ); EIMS m/z: 332, 330 (M)þ (13, 14), 231 (34), 229
(35), 199 (14), 151 (10), 115 (8), 85 (100); HREIMS: calcd
for C14H19O4Br (M)þ: 330.0467, found: 330.0448.
3.1.7. 15-Bromo-13E,8(9)-labdadiene (11). To a solution
of 10 (233 mg, 0.66 mmol) in dry DCM (5.5 mL) was added
CBr4 (230 mg, 0.79 mmol) and PPh3 (289 mg, 1.10 mmol)
at 08C portionwise. The reaction was stirred for 10 min at rt
and diluted with hexane. The mixture was filtered through a
short pad of Celitee, the solvent was evaporated and hexane
was added to the residue in order to remove the PPh3, the
process was repeated three times to give 11 (229 mg, 99%)
as pale yellow oil. IR (film): 1653, 1456, 1387, 1375, 1200,
1119 cm21; 1H NMR d: 5.55 (1H, t, J¼8.4 Hz, H-14), 4.03
(2H, d, J¼8.4 Hz, H-15), 2.20–1.05 (15H, m), 1.74 (3H, s,
Me-16), 1.57 (3H, s, Me-17), 0.94 (3H, s, Me-20), 0.88 (3H,
s, Me-18), 0.83 (3H, s, Me-19); 13C NMR d: 144.5 (C-13),
139.9 (C-9), 126.2 (C-8), 119.8 (C-14), 51.8 (C-5), 41.8
(C-3), 40.2 (C-12), 39.0 (C-10), 37.0 (C-1), 33.6 (C-7), 33.3
(C-4 and C-18), 29.8 (C-15), 26.5 (C-11), 21.7 (C-19), 20.1
(C-20), 19.5 (C 17), 19.0 (C-6 and C-2), 16.0 (C-16); EIMS
m/z: 354, 352 (M)þ (8, 10), 277 (22), 205 (100), 149 (48),
109 (68), 69 (50); HREIMS: calcd for C20H33Br (M)þ:
352.1766, found: 352.1778.
3.1.5. 15-Acetoxy-13E,8(9)-labdadiene (9). To a stirred
solution of 8 (4.55 g, 11.6 mmol) in dry benzene (265 mL)
was added HI (19 mL). After 1 h the mixture was diluted
with Et2O and the organic layer was washed successively
with aqueous solution of NaHCO3 10%, NaHSO3 40%
and water, dried over Na2SO4 and evaporated to give an
oily residue. The purification by silica gel chromatog-
raphy with hexane–AcOEt (95:5) as eluent gave 9
(1.86 g, 48%) as colourless oil. [a]2D0¼þ53 (c¼0.78,
3.1.8. Coupling reaction of 11 with 6:12. To a solution of 6
(433 mg, 1.3 mmol) in THF (4 mL) was added a solution of
tBuLi in pentane (1.7 M, 1.6 mL, 2.8 mmol) at 2788C
under argon. The reaction was stirred for 1 h and 11
(132 mg, 0.4 mmol) was added diluted in THF (4 mL) via
cannula. After 1 h the reaction was quenched by addition of
a saturated aq. solution of NH4Cl (2 mL) and extracted with
Et2O. The organic layer was washed with brine, dried over
Na2SO4 and evaporated to provide an oily residue. This
residue was redissolved in methanol (2 mL) and pTsOH
(245 mg, 1.3 mmol) was added. The mixture was stirred for
1 h then water was added and concentrated under reduced
pressure. The aqueous layer was extracted with Et2O, the
organic layer was washed with aq. solution of NaHCO3 10%
and water, dried over Na2SO4 and evaporated to give an oily
residue. Flash chromatography with benzene–AcOEt (98:2)
as eluent gave 12 (32 mg, 26%) as a colourless oil.
[a]2D0¼þ22 (c¼0.16, CHCl3); IR (film): 3397, 1507, 1458,
CHCl3); IR (film): 1748, 1458, 1387, 1235, 1022 cm21
;
1H NMR d: 5.36 (1H, t, J¼7.0 Hz, H-14), 4.60 (2H, d,
J¼7.0 Hz, H-15), 2.20–1.06 (15H, m), 2.07 (3H, s,
CH3COO), 1.74 (3H, s, Me-16), 1.58 (3H, s, Me-17), 0.94
(3H, s, Me-20), 0.89 (3H, s, Me-18), 0.84 (3H, s, Me-19);
13C NMR d: 171.3 (CH3COO), 143.3 (C-13), 140.2 (C-9),
126.3 (C-8), 117.8 (C-14), 61.6 (C-15), 52.1 (C-5), 42.0
(C-3), 40.4 (C-12), 39.2 (C-10), 37.2 (C-1), 33.8 (C-7), 33.5
(C-4 and C-18), 26.8 (C-11), 21.9 (C-19), 21.3 (CH3COO),
20.3 (C-20), 19.7 (C 17), 19.3 (C-6 and C-2), 16.8 (C-16);
EIMS m/z: 272 (M260)þ (64), 257 (100), 229 (10), 204
(78), 119 (45), 77 (55); HREIMS: calcd for C22H36O2 (M)þ:
332.2715, found: 332.2738.
1
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P. Basabe et al. / Tetrahedron 59 (2003) 9173–9177
9177
NMR d: 7.16 (1H, d, J¼2.0 Hz, H-21), 7.15 (1H, dd, J¼9.2,
2.0 Hz, H-19), 7.04 (1H, d, J¼9.2 Hz, H-18), 5.20 (2H, s,
OCH2O), 4.60 (2H, s, H-22), 3.47 (3H, s, MeO), 3.35 (2H, d,
J¼7.1 Hz, H-15), 2.00–1.80 (5H, m, H-12, H-7 and Ha-1),
1.75 (3H, s, Me-23), 1.60–1.40 (5H, m, H-2, H-6 and Ha-3),
1.57 (3H, s, Me-24), 1.40–1.20 (5H, m, H-11, Hb-3, Hb-1,
H-5), 0.93 (3H, s, Me-25), 0.88 (3H, s, Me-26), 0.83 (3H, s,
Me-27); 13C NMR d: 154.5 (C-17), 140.4 (C-9), 137.0
(C-13), 134.0 (C-20), 131.1 (C-16), 129.5 (C-21), 128.8 (C-
19), 125.7 (C-8), 121.6 (C-14), 113.9 (C-18), 94.3
(OCH2O), 65.2 (C-22), 55.9 (CH3O), 51.9 (C-5), 41.8
(C-3), 40.4 (C-12), 39.0 (C-10), 37.0 (C-1), 33.6 (C-7), 33.3
(C-4 and C-26), 29.6 (C-15), 28.6 (C-11), 21.6 (C-27), 20.1
(C-25), 19.5 (C-24), 19.0 (C-6 and C-2), 16.1 (C-23); EIMS
m/z 441 (MþH)þ (1), 423 (6), 391 (11), 205 (22), 149 (64);
HREIMS: calcd for C29H45O3 (MþH)þ: 441.3369, found:
441.3367.
and brine, dried over Na2SO4 and concentrated to afford a
residue. The purification by silica gel chromatography with
CHCl3 as eluent gave (þ)-subersic acid (9 mg, 47%) as
colourles solid. [a]D20¼þ49 (c¼0.78, CHCl3). IR (film):
3308, 1684, 1607, 1456, 1410, 1387, 1277, 1175, 1123,
1099, 739 cm21; 1H NMR d: 7.90 (1H, d, J¼2.1 Hz, H-21),
7.89 (1H, dd, J¼9.0, 2.1 Hz, H-19), 6.86 (1H, d, J¼9.0 Hz,
H-18), 5.35 (1H, t, J¼7.1 Hz, H-14), 3.42 (2H, d, J¼7.1 Hz,
H-15), 2.15–1.90 (7H, m, H-12, H-11, H-7 and Ha-1), 1.83
(3H, s, Me-23),1.60–1.35 (5H, m, H-2, Ha-3 and H-6), 1.58
(3H, s, Me-24), 1.25–1.10 (3H, m, Hb-1,Hb-3 and H-5),
0.95 (3H, s, Me-25), 0.88 (3H, s, Me-26), 0.87 (3H, s, Me-
27); 13C NMR d: 171.1 (C-22), 159.4 (C-17), 140.6 (C-13),
140.1 (C-9), 132.6 (C-21), 130.4 (C-19), 126.8 (C-16),
126.0 (C-8), 121.6 (C-20), 120.0 (C-14), 115.7 (C-18), 51.9
(C-5), 41.8 (C-3), 40.4 (C-12), 39.0 (C-10), 37.0 (C-1), 33.6
(C-7), 33.3 (C-4 and C-26), 29.6 (C-15), 27.0 (C-11), 21.6
(C-27), 20.1 (C-25), 19.5 (C-24), 19.0 (C-6 and C-2), 16.4
(C-23); FABMS m/z 411 (Mþ1)þ (1), 341 (4), 313 (4), 219
(5), 154 (32). HRFABMS: calcd for C27H39O3: 411.2899,
found: 411.2893. The assignments for the spectra, 1H NMR
and 13C NMR for subersic acid were done by 2D correlation
experiments HMQC and HMBC.
3.1.9. Oxidation of 12:13. To a solution of 12 (32 mg,
0.07 mmol) in dry DCM (10 mL) was added MnO2
(212 mg, 2.4 mmol). The reaction was stirred at rt for 3 h
and then was filtered through a short pad of silica gel and
Celitee, the solvent was removed to afford an oily residue.
Column chromatography on silica gel with hexane–AcOEt
(95:5) as eluent gave 13 (28 mg, 85%) as colourless oil.
[a]2D0¼þ25 (c¼0.65, CHCl3); IR (film): 1651, 1435, 1364,
1248, 1152, 1119, 1080, 949 cm21; 1H NMR d: 9.87 (1H, s,
H-22), 7.70 (1H, d, J¼2.0 Hz, H-21), 7.29 (1H, dd, J¼8.8,
2.0 Hz, H-19), 7.17 (1H, d, J¼8.8 Hz, H-18), 5.30 (2H, s,
OCH2O), 5.30 (1H, t, J¼7.0 Hz, H-14), 3.48 (3H, s, MeO),
3.38 (2H, d, J¼7.0 Hz, H-15), 2.15–1.10 (15H, m), 1.75
(3H, s, Me-23), 1.57 (3H, s, Me-24), 0.93 (3H, s, Me-25),
0.87 (3H, s, Me-26), 0.82 (3H, s, Me-27); 13C NMR d: 191.6
(C-22), 160.2 (C-17), 140.6 (C-13), 138.3 (C-9), 131.8
(C-20), 131.1 (C-21), 130.6 (C-16), 130.4 (C-19), 126.1
(C-8), 120.9 (C-14), 113.4 (C-18), 94.1 (OCH2O), 56.5
(CH3O), 52.1 (C-5), 42.0 (C-3), 40.7 (C-12), 39.2 (C-10),
37.2 (C-1), 33.8 (C-7), 33.6 (C-4 and C-26), 28.8 (C-15),
27.4 (C-11), 21.9 (C-27), 20.3 (C-25), 19.7 (C-24), 19.3
(C-6 and C-2), 16.5 (C-23).
Acknowledgements
The authors thank the CYCIT for financial support (BQU
2002-02049).
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