Sesquiterpene glycosides and phenylpropanoid esters from Phonus arborescens (Carthamus arborescens)

Article abstract of DOI:10.1021/np970122d

The tert-butylmethyl ether extract of the aerial parts of Phonus arborescens (L.) G. Lopez (Carthamus arborescens L.) afforded three new sesquiterpene glycosides, 10-epi-γ-eudesmol β-D-fucopyranoside (1), 10- epi-γ-eudesmol 2'-O-acetyl-β-D-fucopyranoside (2), and 4,5-dioxo-10-epi- 4,5-seco-γ-eudesmol 2'-O-acetyl-β-D-fucopyranoside (3), together with two new phenylpropanoid esters, 3-(3,4-dihydroxyphenyl)propyl myristate (4) and 3-(3,4-dihydroxyphenyl)propyl palmitate (5) in addition to a series of known compounds. The structures of the new compounds were established by spectroscopic and chemical methods.

Full text of DOI:10.1021/np970122d

1026
J . Nat. Prod. 1997, 60, 1026-1030
Sesqu iter p en e Glycosid es a n d P h en ylp r op a n oid Ester s fr om P h on u s
a r bor escen s (Ca r th a m u s a r bor escen s)
Alejandro F. Barrero,*,† Pilar Arteaga,† J ose´ F. Qu´ılez,‡ Ignacio Rodr´ıguez,‡ and M. Mar Herrador†
Instituto de Biotecnologia, Departamento de Qu´ımica Orga´nica, Facultad de Ciencias, Universidad de Granada,
18071 Granada, Spain, and Departamento de Qu´ımica Orga´nica, Facultad de Ciencias Experimentales,
Universidad de Almeria, 04120 Almeria, Spain
Received February 7, 1997X
The tert-butylmethyl ether extract of the aerial parts of Phonus arborescens (L.) G. Lo´pez
(Carthamus arborescens L.) afforded three new sesquiterpene glycosides, 10-epi-γ-eudesmol
â-D-fucopyranoside (1), 10-epi-γ-eudesmol 2′-O-acetyl-â-D-fucopyranoside (2), and 4,5-dioxo-
10-epi-4,5-seco-γ-eudesmol 2′-O-acetyl-â-D-fucopyranoside (3), together with two new phenyl-
propanoid esters, 3-(3,4-dihydroxyphenyl)propyl myristate (4) and 3-(3,4-dihydroxyphenyl)propyl
palmitate (5) in addition to a series of known compounds. The structures of the new compounds
were established by spectroscopic and chemical methods.
In tr od u ction
Continuing our study of the chemical composition of
medicinal plants found in the Spanish South-East and
North Africa,1-4 we present here the results obtained
in the study of Phonus arborescens (L.) G. Lo´pez
(Carthamus arborescens L.) (Fam. Compositae, tribe
Cynereae), a perennial plant which grows in the South
of Spain and Northeast Africa.
Resu lts a n d Discu ssion
Chromatographic separations of the ether extract of
the aerial parts of Phonus arborescens (L.) G. Lo´pez
(Carthamus arborescens L.) led to the isolation of three
new sesquiterpene glycosides, 10-epi-γ-eudesmol â-D-
fucopyranoside (1), 10-epi-γ-eudesmol 2′-O-acetyl-â-D-
fucopyranoside (2), and 4,5-dioxo-10-epi-4,5-seco-γ-
eudesmol 2′-O-acetyl-â-D-fucopyranoside (3), plus two
new phenylpropanoid esters, 3-(3,4-dihydroxyphenyl)-
propyl myristate (4) and 3-(3,4-dihydroxyphenyl)propyl
palmitate (5). The known compounds, 3-(3,4-dihydroxy-
phenyl)propyl stearate (6),5 3-(3,4-dihydroxyphenyl)-
propyl arachidate (7),5 pinocembrin,6,7 5,7-dihydroxy-6-
methoxyflavone,8,9 5-hydroxy-6,7-dimethoxyflavone,9,10
shiromool,11 and germacra-1(10),4-dien-6â-ol12 also were
isolated and identified by comparison of their physical
and spectroscopic data with those reported in the
literature.
Compound 1, a colorless liquid, is the major compo-
nent of the extract. Its molecular formula C21H36O5 was
deduced from its HRCIMS ([M + 1]+, m/z 369.2552). Its
IR spectrum showed hydroxyl group (3398 and 1063
cm-1) and double bond (1652 cm-1) absorptions. The
proton-noise-decoupled 13C-NMR and DEPT spectra
showed signals of five oxygenated methines and of a
methyl geminal to oxygen corresponding to a deoxy
sugar moiety, whereas the rest of the signals indicated
that 1 contained four methyl groups, six methylene
groups, a methine group, and four quaternary carbons
(one oxygenated and two olefinic) corresponding to a
sesquiterpene moiety. Furthermore, the chemical shift
of the methyls in the H-NMR spectrum at δ 1.63, 1.22,
1.19, and 1.04 (one on a double bond, two on an
oxygenated carbon, and the other nonfunctionalized)
allowed us to propose an eudesmane skeleton with a
double bond at C-4 and an oxygenated function at C-
11 for the sesquiterpene moiety.
1
The 1H- and 13C-NMR spectroscopic data of the
triacetylated derivative 1a , obtained by acetylation of
1 with Ac2O/Pyr, indicated that 1 contained a â-fuco-
pyranose moiety. This was deduced from the following
1H-NMR spectrum data: the anomeric proton appears
at δ 4.62 (J ) 7.9 Hz), the protons H-2′, H-3′, H-4′, and
H-5′ appear at δ 5.15 (dd, J 1′-2′ ) 7.8 Hz, J 2′-3′ ) 10.4
Hz), 5.02 (dd, J 2′-3′ ) 10.4 Hz, J 3′-4′ ) 3.5 Hz), 5.21 (dd,
J 3′-4′ ) 3.5 Hz, J 4′-5′ ) 1.0 Hz), and 3.76 (dq, J 4′-5′
)
1.0 Hz, J 5′-6′ ) 6.3 Hz), respectively, and the presence
of a methyl doublet at δ 1.18 (J ) 6.5 Hz, CH3-6′). The
equatorial orientation of H-4′ was determined by the
values of J 3′-4′ and J 4′-5′. In the 13C-NMR spectrum,
the chemical shifts of the six carbons (see the Experi-
mental Section) are in agreement with that identifica-
tion.13 In order to confirm the structure of 1 and to
establish its stereochemistry, the glycoside was hydro-
lyzed in acid medium (HOAc-H2O-dioxane). Once the
crude product was fractionated, the aqueous fraction
yielded, by acetylation with Ac2O/Pyr, a mixture (5:1)
of â- and R-D-fucopyranose tetraacetate. This ratio was
* Author to whom correspondence should be addressed. Phone: 958
243318. Fax: 958 243318. E-mail: afbarre@goliat.ugr.es.
† Instituto de Biotecnologia, Departamento de Qu´ımica Orga´nica,
Universidad de Granada.
1
obtained from the H-NMR spectrum data, and the D
‡ Departamento de Qu´ımica Orga´nica, Universidad de Almeria.
X Abstract published in Advance ACS Abstracts, October 1, 1997.
configuration was determined on the basis of the posi-
S0163-3864(97)00122-5 CCC: $14.00
© 1997 American Chemical Society and American Society of Pharmacognosy

Sesquiterpene Glycosides
J ournal of Natural Products, 1997, Vol. 60, No. 10 1027
F igu r e 1. NOESY correlations for 10.
tive value of its optical rotation.14 From the organic
fraction, the alcohols 10-13 together with the hydro-
carbons 8 and 9 were isolated by CC, with 10 being the
major component.
F igu r e 2. Octant Projection of 3a , 16.
the protons H-8â and H-6â, which requires a â-axial
orientation of the 4-oxopentyl chain. These data cor-
roborate the conformational change which originated in
the cyclohexane ring during the ozonolysis reaction.
The absolute configuration of C-7 and C-10 of 16 was
determined as R and S, respectively, from the positive
Cotton effect observed in its CD spectrum (Figure 2).
Given that the transformations which lead from 1 to
16 via 10 do not modify the configuration in C-7 and
C-10, the same absolute configurations were assigned
to these carbons in 1.
The structures of alcohols 11-13 were deduced from
1
the H- and 13C-NMR data by comparison with those of
10.
1
The IR and H- and 13C-NMR spectroscopic data of 2
were very similar to those of 1, with the difference being
the presence of an acetate group in 2 [1H-NMR δ 1.99,
and 13C-NMR δ 170.1 and 21.2]. The acetate group in
C-2′ was localized based on the value of the chemical
shift of H-2′ (4.89 ppm) in 1H-NMR and the values of
the coupling constants (J 2′-1′ ) 7 Hz, J 2′-3′ ) 9.4 Hz),
which indicate a trans relationship between the proton
on the carbon holding the acetate group and both vicinal
protons. The stereochemistry of C-7 and C-10 was the
same as in 1, since the acetylation of 2 with Ac2O/Pyr
also gave rise to 1a .
Compounds 8 and 9 were isolated as a mixture and
identified by comparison with published spectroscopic
data,15,16 and their presence as hydrolytic products
confirmed the eudesmane skeleton of 1.
Compound 3 showed hydroxyl (3402 cm-1), acetate
(1742 cm-1), and ketone (1702 cm-1) group absorptions
in its IR spectrum. The molecular formula C23H38O8
was deduced from its HRCIMS ([M + 1]+, m/z 443.2649).
1
The IR and H- and 13C-NMR spectra indicated that
1
The H- and 13C-NMR spectroscopic data are, in part,
the alcohol 10 had the structure of 4-eudesmen-11-ol.
Its relative stereochemistry and the conformation of the
bicyclic system were established by NOESY experiment,
similar to those of 2. The signals of the sugar moiety
showed that a moiety of 2′-O-acetyl-â-D-fucopyranose
was present in 3. The rest of the signals established a
seco-eudesmane structure19,20 for the aglycon. So, a
methyl singlet assignable to methyl ketone was ob-
1
following unequivocal assignment of the H-NMR sig-
1
nals by 1H-1H and H-13C COSY experiments, showing
the major correlations in Figure 1. The equatorial
orientation of H-7 is corroborated by the values of the
coupling constants J 6â-7 ) 2.9 Hz and J 6R-7 ) 2.9 Hz.17
Furthermore, the oxymercuration of 10 with mercuric
acetate in THF-H2O mixture (1:1), followed by reduc-
tion of the intermediate mercury complex with NaBH4
in alkaline medium, gave 14 and 15. The formation of
14 and 15 confirmed the trans relationship between the
methyl group at C-10 and the 2-propanol moiety at
C-7.18
1
served at δ 2.12 in the H-NMR spectrum, and the 13C-
NMR spectrum indicated the presence of two keto
groups at δ 214.8 and 208.0, one of which being
assignable to the cyclohexanone carbonyl group. The
acetylation of 3 with Ac2O/Pyr yielded the triacetate 3a ,
whose production by ozonolysis of 1a confirmed the
structure of 3. The CD spectrum of 3a showed a positive
Cotton effect which allowed determination of the abso-
lute configuration of C-7 and C-10 as R and S, respec-
tively (Figure 2). Since the transformation of 3 into 3a
does not alter the configuration in C-7 and C-10, the
same absolute configurations were assigned to these
carbons in 3.
Ozonolysis of 10 led to the formation of the diketone
1
16. The H-NMR signals of 16 were assigned unequivo-
cally by COSY, DQF-COSY, and HETCOR experiments.
The correlation observed between H-14 and H-9R, H-9â,
H-2a, H-2b, and H-1a in its NOESY spectrum deter-
mined an equatorial orientation for Me-14 (δ 21.8 ppm).
The chemical shift of C-1 (18.0 ppm) can be explained
by a cis-diaxial interaction between this methylene and
Compounds 4-7 were identified as a mixture which
could not be separated. Hydroxyl group (3394 cm-1) and
ester group (1736 cm-1) absorptions were observed in
the IR spectrum. The comparison of the 1H-NMR

1028 J ournal of Natural Products, 1997, Vol. 60, No. 10
Barrero et al.
spectroscopic data with those described for 3-(3,4-
dihydroxyphenyl)propyl stearate and 3-(3,4-dihydroxy-
phenyl)propyl arachidate5 allowed us to propose struc-
tures of 3-(3,4-dihydroxyphenyl)propanol esterified with
saturated lineal chain acids of n ) 12-18 for 4-7. The
saponification of 4-7 with 10% KOH/MeOH and sub-
sequent silylation of the acid fraction with BSTFA
allowed the identification of the TMS derivatives of
myristic, palmitic, stearic, and arachidic acids by GC-
MS analysis. The neutral fraction was constituted of
3-(3,4-dihydroxyphenyl)propanol,21 whose triacetylated
derivative showed an [M]+ at m/z 294.
IR (film) ν max 3398 (OH), 2933, 1652 (CdC), 1448,
1
1368, 1216, 1170, 1132, 1063, 997, 755 cm-1; H NMR
(CDCl3, 300 MHz) δ 4.36 (1H, d, J 1′-2′ ) 6.6 Hz, H-1′),
3.57 (4H, m, H-2′-H-5′), 2.54 (1H, dd, J 6R-7 ) 3.8 Hz,
J 6R-6â ) 15.1, H-6R), 1.63 (3H, br s, Me-15), 1.29 (3H,
d, J 6′-5′ ) 6.5 Hz, Me-6′), 1.22 and 1.19 (6H, 2s, Me-12,
Me-13), 1.04 (3H, s, Me-14); 13C NMR (CDCl3, 100 MHz)
δ 134.7 (s, C-4), 124.9 (s, C-5), 97.2 (d, C-1′), 81.2 (s,
C-11), 74.1 (d, C-4′), 72.1 (d, C-3′), 71.7 (d, C-2′), 70.3
(d, C-5′), 44.4 (d, C-7), 38.8, 38.3 (2t, C-1, C-6), 34.2 (s,
C-10), 32.2 (t, C-3), 26.8, 26.2 (2q, C-12, C-13), 24.8 (t,
C-9), 23.3 (q, C-15), 21.9 (t, C-8), 19.7 (q, C-14), 19.1 (t,
C-2), 16.6 (q, C-6′); EIMS (70 eV) m/z 222 [M -
C6H10O4]+ (12), 204 (62), 189 (100), 161 (90), 133 (76),
119 (23), 105 (57), 91 (80), 59 (68); CIMS (CH4) m/z 369
[M + 1]+ (2), 368 (8), 351 (1), 292 (1.5), 206 (49), 205
(100), 203 (75), 189 (29), 149 (44), 123 (16); HRCIMS
(CH4) m/z 369.2552 (calcd for C21H37O5 369.2562).
Exp er im en ta l Section
Gen er a l Exp er im en ta l P r oced u r es. Optical rota-
tions were measured on a 141 Perkin-Elmer polarim-
eter. IR spectra were recorded on a 983G Perkin-Elmer
spectrometer. High-resolution MS were determined on
an Autospec-Q VG-Analytical (FISONS) mass spectrom-
eter, and low-resolution MS were determined on a
5988A Hewlett-Packard mass spectrometer. NMR spec-
tra were recorded on Bruker ARX 400 or Bruker AMX
300 spectrometers (δ values given in ppm relative to
internal TMS and J values in Hz). GC-MS analyses
were carried out in a Hewlett-Packard 5890A using an
ionization voltage of 70 eV. The GC conditions were as
follows: HP-1 capillary column (25 m × 0.32 mm)
packed with methyl silicone, temperature programmed
from 120 to 220 °C at 5 °C min-1, 220 to 280 °C at 3 °C
min-1, and 10 min hold at 280 °C, injector temperature
260 °C, detector temperature 180 °C, He at 25 mL
min-1. Column chromatography was carried out using
silica gel 60 Chromagel (35-70 µm), eluting with
mixtures of hexane/tert-butylmethyl ether, tert-butyl-
methyl ether/ethyl acetate, and ethyl acetate/methanol
of increasing polarity. Analytical TLC was performed
on layers of silica gel Merck 60G of 0.25 mm thickness,
using a 7% phosphomolybdic acid solution (EtOH) to
visualize the spots.
P la n t Ma ter ia l. P. arborescens (L.) G. Lo´pez (C.
arborescens L.) was collected in the Alhamilla Mountain
Range (Almeria, Spain) in May 1994 and identified by
Prof. J . Molero, Professor Titular of the Department of
Vegetable Biology, University of Granada. A voucher
specimen (GDA 9968) is available for inspection at the
herbarium of the Faculty of Pharmacy of the University
of Granada.
Extr a ction a n d Isola tion . The air-dried aerial
parts (2.2 kg) of P. arborescens (L.) G. Lo´pez were
submerged in tert-butylmethyl ether for 6 min. Re-
moval of the solvent under vacuum gave 41.5 g of
residue, which was chromatographed on a Si gel column,
affording germacra-1(10),4-dien-6â-ol (764 mg), pinocem-
brin (870 mg), a mixture of 3-(3,4-dihydroxyphenyl)-
propyl myristate (4), palmitate (5), and stearate (6), plus
arachidate (7) (417 mg), shiromool (87 mg), 5,7-dihy-
droxy-6-methoxyflavone (391 mg), 5-hydroxy-6,7-di-
methoxyflavone (388 mg), 7-epi-γ-eudesmol 2′-O-acetyl-
â-D-fucopyranoside (2) (5.4 g), 7-epi-γ-eudesmol â-D-
fucopyranoside (1) (7.4 g), and 4,5-dioxo-10-epi-4,5-seco-
γ-eudesmol 2′-O-acetyl-â-D-fucopyranoside (3) (92 mg).
The acetyl derivatives were obtained by acetylation with
Ac2O in pyridine.
Acetyla tion of Com p ou n d 1. To a solution of 1 (100
mg) in 1 mL of pyridine was added Ac2O (1 mL), and
the mixture was kept at room temperature for 12 h.
After the usual workup 1a (126 mg) was isolated.
Com p ou n d 1a was obtained as a colorless syrup:
[R]20 -4.3° (c 1, CHCl3); IR (film) ν max 2976, 2936,
D
2867, 1754 (CO acetate), 1660, 1645 (CdC), 1457, 1436,
1369, 1250, 1225, 1172, 1144, 1129, 1074, 1021, 756
1
cm-1; H NMR (CDCl3, 300 MHz) δ 5.21 (1H, dd, J 4′-5′
) 1.0 Hz, J 4′-3′ ) 3.5 Hz, H-4′), 5.15 (1H, dd, J 2′-1′
)
7.8 Hz, J 2′-3′ ) 10.4 Hz, H-2′), 5.02 (1H, dd, J 3′-4′ ) 3.5
Hz, J 3′-2′ ) 10.4 Hz, H-3′), 4.62 (1H, d, J 1′-2′ ) 7.8 Hz,
H-1′), 3.76 (1H, dq, J 5′-4′ ) 1 Hz, J 5′-6′ ) 6.3 Hz, H-5′),
2.40 (1H, dd, J 6R-7 ) 5.1 Hz, J 6R-6â ) 15.6 Hz, H-6R),
2.17, 2.02, 1.98 (9H, 3s, 3 COCH3), 1.59 (3H, br s, Me-
15), 1.21, 1.12 (6H, 2s, Me-12, Me-13), 1.18 (3H, d, J 6′-5′
) 6.3 Hz, Me-6′), 1.03 (3H, s, Me-14); 13C NMR (CDCl3,
100 MHz) δ 170.8, 170.3, 169.2 (3s, 3 COCH3), 134.1 (s,
C-4), 124.9 (s, C-5), 95.3 (d, C-1′), 81.3 (s, C-11), 71.8
(d, C-4′), 70.5 (d, C-3′), 69.4 (d, C-2′), 68.7 (d, C-5′), 44.2
(d, C-7), 39.0 (t, C-1), 38.2 (t, C-6), 34.0 (s, C-10), 32.2
(t, C-3), 27.0, 25.6 (2q, C-12, C-13), 24.7 (t, C-9), 22.7
(q, C-15), 21.8 (t, C-8), 20.9, 20.8, 20.7 (3q, 3 COCH3),
19.7 (q, C-14), 19.2 (t, C-2), 16.3 (q, C-6′); EIMS (70 eV)
m/z 273 (4), 204 (100), 189 (31), 161 (34), 149 (25), 123
(7), 111 (10), 81 (6), 55 (4), 43 (42); CIMS (CH4) m/z 495
[M + 1]+ (0.5), 494 (1), 376 (1), 315 (1.5), 289 (3), 273
(77), 205 (100), 204 (96), 189 (19), 161 (22), 149 (31).
Hyd r olysis of Com p ou n d 1. Glycoside 1 (4.43 g)
was hydrolyzed in 124 mL of dioxane-H2O-HOAc (1:
1:2) at 80 °C for 14 h. EtOAc and H2O were added, and
the aqueous layer was evaporated under reduced pres-
sure and treated with excess Ac2O-pyridine, to yield
R- and â-D-fucopyranose tetraacetate. Of the organic
layer 8 plus 9 (481 mg), 10 (766 mg), 11 (30 mg), 12 (81
mg), and 13 (11 mg) were isolated by silica gel CC,
eluting with mixtures of hexane/tert-butylmethyl ether
of increasing polarity.
Com p ou n d 10 was obtained as an oil: [R]20D -55.8°
(c 1, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 2.69 (1H, br
dd, J 6R-7 ) 2.9 Hz, J 6R-6â ) 14.9 Hz, H-6R), 2.10 (1H,
dd, J 6â-7 ) 2.9 Hz, J 6â-6R ) 14.9 Hz, H-6â), 1.92 (2H,
m, H-3R, H-3â), 1.68 (4H, m, H-9â, H-8â, H-8R, H-2R),
1.66 (3H, br s, Me-15), 1.55 (1H, m, H-2â), 1.39 (1H, br
t, J 1â-2 ) 3.9 Hz, H-1â), 1.33 (1H, br dd, J 1R-2R ) 3.7
Hz, J 1R-2â, ) 11.8 Hz, H-1R), 1.29 (1H, br t, J 9R-8 ) 4.1
Hz, H-9R), 1.23, 1.17 (6H, 2s, Me-12, Me-13), 1.07 (3H,
7-Ep i-γ-eu d esm ol â-D-fu cop yr a n osid e (1) was ob-
tained as a colorless syrup: [R]20 -27.1° (c 1, CHCl3);
D

Sesquiterpene Glycosides
J ournal of Natural Products, 1997, Vol. 60, No. 10 1029
s, Me-14). The IR, EIMS, and 13C NMR data were in
agreement with those of the literature.17
Me-14); 13C NMR (CDCl3, 75 MHz) δ 74.6 (s, C-11), 72.9
(s, C-4), 44.6 (d, C-5), 42.8 (d, C-7), 42.2 (t, C-9), 41.0 (t,
C-1), 32.1 (t, C-3), 31.0, 29.7, 29.1 (3q, C-12, C-13, C-15),
29.4 (t, C-6), 25.2 (t, C-8), 22.1 (t, C-2), 17.8 (q, C-14);
EIMS (70 eV) m/z 207 [M - Me]+ (100), 189 (24), 164
(7), 149 (29), 133 (9), 123 (13), 109 (81), 95 (13), 93 (14),
81 (19), 43 (37).
Com p ou n d 11 was obtained as a colorless syrup:
[R]20D -17.1° (c 0.66, CHCl3); IR (film) ν max 3402 (OH),
2967, 2924, 1652 (CdC), 1457, 1375, 1150, 916 cm-1
;
1H NMR (CDCl3, 400 MHz) δ 5.30 (1H, dt, J 6-4 ) 1.9
Hz, J 6-7 ) 5.6 Hz, H-6), 1.20, 1.18 (6H, 2s, Me-12, Me-
13), 0.95 (3H, s, Me-14), 0.85 (3H, d, J 15-4 ) 6.6 Hz,
Me-15); 13C NMR (CDCl3, 100 MHz) δ 144.7 (s, C-5),
118.6 (d, C-6), 72.7 (s, C-11), 44.3 (d, C-7), 41.3 (d, C-4),
38.9 (t, C-9), 38.7 (s, C-10), 32.5, 31.2 (2t, C-3, C-1), 27.7,
27.4 (2t, C-2, C-8), 27.5, 26.3 (2q, C-12, C-13), 18.0 (q,
C-14), 15.8 (q, C-15); EIMS (70 eV) m/z 222 [M]+ (5),
204 (50), 189 (50), 161 (100), 149 (28), 135 (25), 123 (40),
119 (55), 107 (39), 93 (38), 59 (91), 43 (40).
Ozon olysis of Com p ou n d 10. A slow O3/O2 mixture
was bubbled for 1 h through a stirred solution of 10 (120
mg) in CH2Cl2 (10 mL) at -78 °C. The mixture was
flushed with argon and after addition of Me2S (1 mL)
was kept at room temperature for 12 h and then
evaporated under vacuum. The crude product was
column chromatographed. Elution with hexane/tert-
butylmethyl ether 50:50 yielded 16 (85 mg).
Com p ou n d 12 was obtained as a colorless syrup:
Com p ou n d 16 was obtained as a colorless syrup:
[R]20D +68.4° (c 0.53, CHCl3); IR (film) ν max 3406 (OH),
2967, 1700 (CO ketone), 1463, 1376, 1248, 1166, 1127,
1027, 951, 926 cm-1; 1H NMR (CDCl3, 300 MHz) δ 2.40
(4H, m, H-3, H-6), 2.09 (3H, s, H-15), 1.87 (1H, dt, J 9â-8
) 3.1 Hz, J 9â-9R ) 13.6 Hz, H-9â), 1.72 (1H, br t, J )
3.3 Hz, H-2a), 1.70 (2H, m, H-8), 1.64 (1H, m, H-7), 1.55
[R]20 -7.9° (c 0.63, CHCl3); IR (film) ν max 3486 (OH),
D
2929, 1650 (CdC), 1466, 1369, 1257, 1216, 1169, 1139,
1053, 1010, 969, 858 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 2.42 (1H, dd, J 6R-7 ) 2.4 Hz, J 6R-6â ) 14.0 Hz, H-6R),
1.62 (3H, br s, Me-15), 1.00 (3H, s, Me-14), 0.96, 0.95
(6H, 2d, J ) 6.9 Hz, Me-12, Me-13); 13C NMR (CDCl3,
75 MHz) δ 130.9 (s, C-5), 128.8 (s, C-4), 74.8 (s, C-7),
40.1 (t, C-1), 37.8 (d, C-11), 37.6 (t, C-9), 34.1 (t, C-6),
33.8 (t, C-3), 29.7 (s, C-10), 29.3 (t, C-8), 24.1 (q, C-15),
19.5 (q, C-14), 19.2 (t, C-2), 17.3, 17.0 (2q, C-12, C-13);
EIMS (70 eV) m/z 222 [M]+ (6), 204 (1), 179 (7), 123
(100), 91 (6), 43 (10).
(1H, m, H-1a), 1.44 (1H, m, H-9R), 1.32 (1H, br dd, J 1
)
3.3 Hz, J 2 ) 12.5 Hz, H-2b), 1.25 (1H, m, H-1b), 1.20,
1.19 (6H, 2s, H-12, H-13), 0.99 (3H, s, H-14); 13C NMR
(CDCl3, 75 MHz) δ 215.8 (s, C-5), 208.3 (s, C-4), 72.0 (s,
C-11), 50.1 (d, C-7), 47.9 (s, C-10), 43.6 (t, C-3), 39.9 (t,
C-6), 38.4 (t, C-9), 36.9 (t, C-2), 29.9 (q, C-15), 27.5, 27.2
(2q, C-12, C-13), 21.8 (q, C-14), 21.6 (t, C-8), 18.0 (t, C-1);
EIMS (70 eV) m/z 239 [M - CH3]+ (0.7), 221 (2), 196
(14), 178 (12), 170 (16), 152 (15), 136 (10), 135 (34), 112
(68), 111 (68), 95 (13), 84 (11), 81 (17), 69 (20), 59 (62),
43 (100).
Com p ou n d 13 was obtained as a colorless syrup:
[R]20 -16.0° (c 1, CHCl3); IR (film) ν max 3422 (OH),
D
2959, 1652 (CdC), 1457, 1375, 1121, 996, 947 cm-1; 1H
NMR (CDCl3, 300 MHz) δ 2.76 (1H, dd, J 6R-7 ) 2.9 Hz,
J 6R-6â ) 13.5 Hz, H-6R), 1.61 (3H, br s, Me-15), 1.07
(3H, s, Me-14), 0.92, 0.82 (6H, 2d, J ) 6.9 Hz, Me-12,
Me-13); 13C NMR (CDCl3, 75 MHz) δ 132.6 (s, C-5),
126.8 (s, C-4), 75.6 (s, C-7), 44.2 (d, C-11), 39.9 (t, C-1),
38.3 (t, C-6), 37.1 (t, C-9), 32.9, 32.8 (2t, C-3, C-8), 29.9
(s, C-10), 25.1 (q, C-15), 19.7 (q, C-14), 19.0 (t, C-2), 16.6;
16.1 (2q, C-12, C-13); EIMS (70 eV) m/z 222 [M]+ (7),
204 (2), 179 (8), 123 (100), 91 (7), 43 (14).
7-Ep i-γ-eu d esm ol 2′-O-a cetyl-â-D-fu cop yr a n osid e
(2) was obtained initially as a syrup, which slowly
crystallizes: mp 110-112 °C; [R]20 +2.6° (c 1, CHCl3);
D
IR (film) ν max 3430 (OH), 2929, 1745 (CO acetate),
1652 (CdC), 1456, 1369, 1239, 1167, 1134, 1063, 998,
1
753 cm-1; H NMR ((CD3)2CO, 300 MHz) δ 4.89 (1H,
dd, J 2′-1′ ) 8.0 Hz, J 2′-3′ ) 9.4 Hz, H-2′), 4.57 (1H, d,
J 1′-2′ ) 7.9 Hz, H-1′), 3.89, 3.82 (2H, 2 br s, 2OH), 3.66
(3H, m, H-3′, H-4′, H-5′), 2.46 (1H, dd, J 6R-7 ) 5.1 Hz,
J 6R-6â ) 15.5 Hz, H-6R), 1.99 (3H, s, COCH3), 1.58 (3H,
br s, Me-15), 1.22 (3H, d, J 6′-5′ ) 6.5 Hz, Me-6′), 1.17,
1.15 (6H, 2s, Me-12, Me-13), 1.02 (3H, s, Me-14); 13C
NMR ((CD3)2CO, 75 MHz) δ 170.1 (s, COCH3), 134.9 (s,
C-4), 125.1 (s, C-5), 95.8 (d, C-1′), 80.6 (s, C-11), 73.5,
73.2 (2d, C-2′, C-4′), 72.6 (d, C-3′), 70.6 (d, C-5′), 45.0
(d, C-7), 39.6, 38.8 (2t, C-1, C-6), 34.5 (s, C-10), 32.7 (t,
C-3), 27.2, 25.7 (2q, C-12, C-13), 25.4 (t, C-9), 23.2 (q,
C-15), 22.8 (t, C-8), 21.2 (q, COCH3), 19.8 (q, C-14), 19.7
(t, C-2), 16.9 (q, C-6′); CIMS (CH4) m/z 411 [M + 1]+
(0.6), 410 (2), 245 (0.6), 206 (27.5), 205 (100), 203 (41),
189 (61), 171 (17), 149 (24), 43 (10); HRICMS (CH4) m/z
411.2754 (calcd for C23H39O6 411.2746).
Oxym er cu r a tion -Dem er cu r a tion of Com p ou n d
10. Mercuric acetate (257 mg) and 10 (179 mg) were
dissolved in a mixture of THF (6 mL) and H2O (2 mL).
After 6 h at room temperature, 19.2 mg of NaBH4
dissolved in 1.6 mL of 3 N NaOH was added, and the
reaction mixture was kept at room temperature for 1
h. After the usual workup 14 (50 mg) and 15 (22 mg)
were isolated by silica gel CC, eluting with hexane/tert-
butylmethyl ether 98:2.
Com p ou n d 14 was obtained as a colorless oil: [R]20
D
-51.1° (c 1, CHCl3); IR (film) ν max 2968, 2927, 2860,
1427, 1380, 1144, 1019, 997, 887 cm-1; 1H NMR (CDCl3,
300 MHz) δ 2.07 (1H, dd, J 6R-7 ) 4.6 Hz, J 6R-6â ) 11.9
Hz, H-6R), 1.79 (1H, m, H-4), 1.37, 1.15 (6H, 2s, Me-12,
Me-13), 0.99 (3H, s, Me-14), 0.88 (3H, d, J 15-4 ) 6.6 Hz,
Me-15); 13C NMR (CDCl3, 75 MHz) δ 87.3 (s, C-5), 81.1
(s, C-11), 43.8 (d, C-7), 38.7 (s, C-10), 38.1 (t, C-6, C-9),
36.1 (t, C-1), 33.4 (t, C-3), 32.2 (d, C-4), 30.3, 23.5 (2q,
C-12, C-13), 25.1 (t, C-8), 23.0 (q, C-14), 21.4 (t, C-2),
15.7 (q, C-15); EIMS (70 eV) m/z 222 [M]+ (8), 207 (100),
189 (28), 164 (14), 149 (25), 137 (58), 109 (43), 95 (24),
81 (24), 69 (30), 55 (40), 41 (50).
4,5-Dioxo-10-ep i-4,5-seco-γ-eu d esm ol 2′-O-a cetyl-
â-D-fu cop yr a n osid e (3) was obtained as a colorless
syrup: [R]20D + 19.5° (c 1, CHCl3); IR (film) ν max 3402
(OH), 2930, 1742 (CO acetate), 1702 (CO ketone), 1448,
1
1369, 1241, 1168, 1136, 1063, 998, 751 cm-1; H NMR
((CD3)2CO, 400 MHz) δ 4.93 (1H, dd, J 2′-1′ ) 7.9 Hz,
J 2′-3′ ) 8.7 Hz, H-2′), 4.58 (1H, d, J 1′-2′ ) 7.9 Hz, H-1′),
3.77 (3H, m, H-3′, H-4′, H-5′), 2.46 (2H, t, J 3-2 ) 6.7
Hz, H-3), 2.27 (1H, dd, J 6R-7 ) 3.0 Hz, J 6R-6â ) 11.7
Hz, H-6R), 2.06, 2.02 (6H, 2s, COCH3, Me-15), 1.23 (3H,
1
Com p ou n d 15: H NMR (CDCl3, 300 MHz) δ 2.27
(1H, dd, J 6R-7 ) 5.3 Hz, J 6R-6â ) 13.8 Hz, H-6R), 1.30,
1.26, 1.22 (9H, 3s, Me-12, Me-13, Me-15), 0.99 (3H, s,

1030 J ournal of Natural Products, 1997, Vol. 60, No. 10
Barrero et al.
d, J 6′-5′ ) 6.5 Hz, Me-6′), 1.21, 1.18 (6H, 2s, Me-12, Me-
13), 0.91 (3H, s, Me-14); 13C NMR ((CD3)2CO, 100 MHz)
δ 214.8 (s, C-5), 208.0 (s, C-4), 170.2 (s, COCH3), 96.0
(d, C-1′), 78.6 (s, C-11), 73.4, 73.0 (2d, C-2′, C-4′), 72.6
(d, C-3′), 70.8 (d, C-5′), 50.4 (d, C-7), 48.3 (s, C-10), 43.6
(t, C-3), 39.8, 39.2 (2t, C-6, C-9), 36.8 (t, C-2), 29.8 (q,
C-15), 25.4 (q, C-14), 23.1, 22.0 (2q, C-12, C-13), 21.9 (t,
C-8), 21.2 (q, COCH3), 18.6 (t, C-1), 16.9 (q, C-6′); CIMS
(CH4) m/z 443 [M + 1]+ (1), 265 (2), 255 (12), 237 (33),
231 (3), 219 (21), 201 (8), 189 (53), 177 (8), 171 (21), 129
(14), 111 (21), 85 (27), 59 (41), 43 (100); HRCIMS (CH4)
m/z 443.2649 (calcd for C23H39O8 443.2644).
Hyd olysis of Com p ou n d s 4-7. A mixture of 4-7
(98 mg) was dissolved in 2 N KOH in MeOH (5 mL).
The solution was kept at room temperature for 12 h.
After most of the MeOH was removed and diluted with
H2O (50 mL), the solution was extracted with Et2O,
yielding 3-(3,4-dihydroxyphenyl)propanol24 (17 mg). The
residual aqueous solution was acidified with 2 N HCl
(pH 2) and extracted with Et2O, giving a mixture of
myristic, palmitic, stearic, and arachidic acids (42 mg).
Pyridine (20 mL) and BSTFA (40 mL) were added to 2
mg of the acid mixture, and it was maintained at 110
°C for 30 min obtaining the TMSi derivatives, which
were identified by GC-MS analysis.
Acetyla tion of Com p ou n d 3. Following the same
procedure described for 1, compound 3 (50 mg) was
acetylated to yield 3a (52 mg).
Ack n ow led gm en t. We acknowledge the J unta de
Andalucia (Project “Chemical and Biological Study of
Aromatic and Medicinal Plant from Andalucia and
Morocco”) for financial support and Professor M. Grande,
Department of Organic Chemistry, Faculty of Science,
University of Salamanca (Spain) for measuring the CD
spectra.
Com p ou n d 3a was obtained as a colorless syrup:
[R]20 +42.2° (c 0.7, CHCl3); IR (film) ν max 2934, 1749
D
(CO acetate), 1703 (CO ketone), 1458, 1368, 1250, 1225,
1171, 1145, 1127, 1072, 971 cm-1; 1H NMR (CDCl3, 300
MHz) δ 5.20 (1H, dd, J 4′-5′ ) 1.1 Hz, J 4′-3′ ) 3.5 Hz,
H-4′), 5.14 (1H, dd, J 2′-1′ ) 7.7 Hz, J 2′-3′ ) 10.5 Hz, H-2′),
5.00 (1H, dd, J 3′-4′ ) 3.5 Hz, J 3′-2′ ) 10.5 Hz, H-3′), 4.57
(1H, d, J 1′-2′ ) 7.7 Hz, H-1′), 3.74 (1H, dq, J 5′-4′ ) 1.1
Hz, J 5′-6′ ) 6.4 Hz, H-5′), 2.43 (2H, t, J 3-2 ) 7.0 Hz,
H-3), 2.37 (1H, br d, J 6R-6â ) 11.0 Hz, H-6R), 2.17, 2.11,
2.02, 1.96 (12H, 4s, 3COCH3, Me-15), 1.18 (3H, d, J 6′-5′
Refer en ces a n d Notes
(1) Barrero, A. F.; Herrador, M. M.; Molina Molina, J .; Qu´ılez, J .
F.; Quiro´s, M. J . Nat. Prod. 1994, 57, 873-881.
(2) Barrero, A. F.; Herrador, M. M.; Arteaga, P. Phytochemistry
1994, 37, 1351-1358.
(3) Barrero, A. F.; Cabrera, E.; Rodr´ıguez, I.; Ferna´ndez-Gallego,
E. Phytochemistry 1994, 36, 189-194.
(4) Barrero, A. F.; Herrador, M. M.; Ha¨ıdour, A.; Altarejos, J .;
Arteaga, P.; Chaboun, R. Tetrahedron Lett. 1995, 36, 2649-2652.
(5) Bohlmann, F.; Zdero, C.; King, R. M.; Robinson, H. Phytochem-
istry 1981, 20, 1657-1663.
(6) J ung, J . H.; Pummangura, S.; Chaichantipyuth, C.; Patarapan-
ich, C.; Mc Laughlin, J . L. Phytochemistry 1990, 29, 1667-1670.
(7) Nagarajan, G. R.; Parmar, V. S. Planta Medica 1977, 31, 146-
150.
(8) El-Din, A. S. Acta Pharm. J ugosl. 1987, 37, 97-101.
(9) Khafagy, S.; Sabri, N. N.; Salam, N. A.; El-Din, A. S.; Blessing-
ton, B. Acta Pharm. J ugosl. 1979, 29, 161-165.
(10) Stierle, D. B.; Stierle, A. A.; Larsen, R. D. Phytochemistry 1988,
27, 517-522.
(11) Wada, K.; Enomoto, Y.; Munakata, K. Agric. Biol. Chem. 1970,
34, 946-953.
(12) Bohlmann, F.; Knoll, K.-H.; Zdero, C.; Kumar Mahanta, P.;
Grenz, M.; Suwita, A.; Ehlers, D.; Levan, N.; Abraham, W.-R.;
Anant Natu, A. Phytochemistry 1977, 16, 965-985.
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J . M.; Barrero, A. F. Phytochemistry 1990, 29, 3207-3211 and
references cited therein.
) 6.5 Hz, Me-6′), 1.21, 1.17 (6H, 2s, Me-12, Me-13); 13
C
NMR (CDCl3, 75 MHz) δ 215.7 (s, C-4), 208.5 (s, C-5),
170.8, 170.3, 169.3 (3s, 3COCH3), 95.6 (d, C-1′), 78.9 (s,
C-11), 71.6 (d, C-4′), 70.4 (d, C-3′), 69.2, 69.0 (2d, C-2′,
C-5′), 49.6 (d, C-7), 47.9 (s, C-10), 43.7 (t, C-3), 39.4 (t,
C-6), 38.2 (t, C-9), 36.3 (t, C-2), 29.9 (q, C-15), 25.1 (q,
C-14), 23.4, 21.7 (2q, C-12, C-13), 21.2 (t, C-8), 20.9, 20.8,
20.7 (3q, 3COCH3), 18.2 (t, C-1), 16.3 (q, C-6′); CIMS
(CH4) m/z 527 [M + 1]+ (11), 442 (4), 347 (1), 289 (1),
274 (20), 273 (100), 265 (13), 238 (23), 237 (99), 219 (35),
153 (37), 111 (19), 83 (16).
Ozon olysis of Com p ou n d 1a . Following the same
procedure described for 10, compound 1a (60 mg) was
ozonized to yield a crude product which, after column
chomatography, afforded 3a (48 mg).
3-(3,4-Dih yd r oxyp h en yl)p r op yl m yr ista te, p a lm -
ita te, stea r a te, a n d a r a ch id a te (4-7) were obtained
as an oily mixture: IR (film) ν max 3394 (OH), 2920,
2851, 1736 (CO ester), 1638, 1513, 1466, 1368, 1282,
1175, 1114 cm-1; 1H NMR (CDCl3, 300 MHz) δ 6.76 (1H,
d, J ) 8.0 Hz, H-5), 6.70 (1H, d, J ) 2.0 Hz, H-2), 6.59
(1H, dd, J 1 ) 2.0 Hz, J 2 ) 8.0 Hz, H-6), 4.06 (2H, t, J )
6.5 Hz, H-9), 2.56 (2H, t, J ) 7.5 Hz, H-7), 2.29 (2H, t,
J ) 7.5 Hz, H-2′), 1.89 (2H, tt, J 1 ) 6.5 Hz, J 2 ) 7.5 Hz,
H-8), 1.60 (2H, m, H-3′), 1.25 (2xH, br s, (CH2)x), 0.88
(3H, t, J ) 6.8 Hz, Me); 13C NMR (CDCl3, 75 MHz) δ
174.2 (s, C-1′), 143.7 (s, C-4), 141.8 (s, C-3), 134.3 (s,
C-1), 120.8 (d, C-6), 115.5, 115.4 (2d, C-2, C-5), 63.6 (t,
C-9), 34.4 (t, C-2′), 32.0 (t, CH2CH2CH3), 31.5 (t, C-7),
30.4 (t, C-8), 29.7, 29.5, 29.4, 29.3, 29.2 (5t, (CH2)x), 25.1
(t, C-3′), 22.7 (t, CH2CH2CH3), 14.1 (q, Me).
(14) Carbohydrates; Collins, P. M., Ed.; Chapman and Hall: London,
1987; p 226.
(15) Klein, E.; Rojahn, W. Tetrahedron Lett. 1970, 279-282.
(16) Sun, H. H.; Erickson, K. L. J . Org. Chem. 1978, 43, 1613-1614.
(17) Su, W.-C.; Fang, J .-M.; Cheng, Y.-S. Phytochemistry 1995, 39,
603-607.
(18) Baker, R.; Evans, D. A.; Mc Dowell, Ph.G. J . Chem. Soc., Chem
Commun. 1977, 111.
(19) Bohlmann, F.; Zdero, C.; King, R. M.; Robinson, H. Liebigs Ann.
Chem. 1983, 2227-2246.
(20) Appendino, G.; Gariboldi, P.; Callin, M.; Chiari, G.; Viterbo, D.
J . Chem. Soc., Perkin Trans. 1 1983, 2705-2709.
(21) Cardona, M. L.; Garcia, B.; Pedro, R. J .; Sinisterra, J . F.
Phytochemistry 1990, 29, 629-631.
NP970122D