First efficient synthesis of chlorogenic acid

Article abstract of DOI:10.1002/1099-0690(200103)2001:6<1137::AID-EJOC1137>3.0.CO;2-2

The first efficient synthesis of chlorogenic acid (1) was achieved in four steps (three purifications) from quinic acid (2). The overall yield was 65%, The key intermediate was quinic acid bisacetonide (6), selectively prepared by a modified kinetic aceta

Full text of DOI:10.1002/1099-0690(200103)2001:6<1137::AID-EJOC1137>3.0.CO;2-2

FULL PAPER
First Efficient Synthesis of Chlorogenic Acid
Michael Sefkow[a]
Keywords: Chlorogenic acid / Natural products / Acylation / Acetalization / Antioxidant
The first efficient synthesis of chlorogenic acid (1) was
achieved in four steps (three purifications) from quinic acid protecting groups of 12 was accomplished in one step under
(2). The overall yield was 65%. The key intermediate was
acidic conditions. The progress of the hydrolysis was moni-
feic acid chloride (3) afforded ester 12. Cleavage of all the
quinic acid bisacetonide (6), selectively prepared by a modi- tored by MALDI-MS.
fied kinetic acetalization protocol. Esterification of 6 with caf-
Introduction
a quinide acetal with the wrong hydroxy group unprotected.
This required several protecting group manipulations and
acidic and basic hydrolysis as the final steps of the syn-
thesis.[9] Basic hydrolysis, in particular, should be avoided
because chlorogenic acid is very sensitive to oxidation in
basic solutions. Recently, the synthesis of a series of chlor-
ogenic acid analogs was reported by Hemmerle et al.[10]
Good overall yields (22Ϫ32%) of these analogs were
achieved by using only acid-labile protecting groups, al-
though a quinide acetal (Figure 2) was again used as the
quinic acid intermediate. Key features for a short synthesis
of 1 in high overall yield would therefore be a properly func-
tionalised quinic acid derivative and the use of only acid-
labile protecting groups (Scheme 1).
3-Caffeoyl quinic acid (1; Figure 1), chlorogenic acid, and
the 1-, 4-, and 5-regioisomers are common secondary plant
metabolites.[1] Particulary high contents of 1 and its con-
geners are found in coffee (up to 7%), potatoes, and many
fruits and vegetables.[1] Humans consuming plant-rich food
and drinking more than one cup of coffee a day may ingest
up to 1 g of chlorogenic acids per day.[1] Chlorogenic acid
(1) has many biological activities.[2] Most important, it has
antibacterial, antimutagenic, antitumor, and antiviral prop-
erties.[3] The pharmacophore responsible for the biological
function is the catechol moiety in 1. This ortho-diphenyl
group acts as a radical scavenger,[4] and as an antioxidant.[5]
Despite their importance as non-nutritive food constituents,
relatively little is known about the metabolism of caffeoyl
quinic acids in mammals.[2,6] Studies on the metabolism of
1 are limited because isotope labeled chlorogenic acids are
not readily available and efficient syntheses of 1, or labeled
derivatives thereof, have not been reported.
Figure 2. Quinide acetals formed by common acetalization pro-
cesses
Figure 1. 3-Caffeoylquinic acid (chlorogenic acid)
Scheme 1. Key intermediates for a synthesis of chlorogenic acid 1
(R, RЈ ϭ acid labile)
Herein we describe a short and efficient synthesis of chlo-
rogenic acid (1) starting from quinic and caffeic acid.
A suitably protected and activated caffeic acid was di-O-
acetylcaffeoyl chloride (3)[11] obtained from caffeic acid (4)
after optimization of standard procedures. Acylation of 4
with Ac2O in pyridine and chlorination with two equiva-
lents of oxalyl chloride provided the acid chloride 3 in 93%
overall yield after recrystallization (Scheme 2).
Results and Discussion
The first and so-far only chemical[7] synthesis of chlorog-
enic acid (1) was reported by Panizzi et al. 45 years ago.[8]
The natural product was prepared in seven steps from
quinic acid (2) but the overall yield was low (Ͻ5%). The
major disadvantage of this synthesis was the formation of
[a]
Institut für Organische Chemie und Strukturanalytik,
Universität Potsdam,
Karl-Liebknecht-Strasse 24Ϫ25, 14476 Golm, Germany
Fax: (internat.) ϩ49-331/977-5067
E-mail: sefkow@rz.uni-potsdam.de
Scheme 2. Optimized synthesis of caffeic acid chloride 3
Eur. J. Org. Chem. 2001, 1137Ϫ1141
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/0306Ϫ1137 $ 17.50ϩ.50/0
1137

M. Sefkow
FULL PAPER
The acid-catalyzed acetalization of (Ϫ)-quinic acid (2) ried (Table 1). Increasing the amount of acetone (9 equiv.)
under thermodynamic conditions generally afford the quin- or TMS-OTf (20 mol-%), lowering the initial reaction tem-
ide acetal (Figure 2) in good yields (75 to 90%).[12,13] Re- perature (Ϫ95 °C) or maintaining the reaction at Ϫ75 °C
cently, Rohloff et al. reported that transformation of 2 un- did not improve the yield of bisacetonide 6. Only the ratio
der those conditions in a mixture of acetone and 2,2-dime- of quinide 5 and mesityl adduct 8 varied (entries 2Ϫ4).
thoxypropane (DMP) yielded, beside quinide acetal 5, bisa- Even if the reaction was carried out in acetone, the ratio of
cetonide
6 as a
minor product (Scheme 3).[14] This 5, 6, and 8 was almost unchanged but, additionally, an ad-
bisacetonide would be the ideal quinic acid derivative be- duct of 6 and phorone, compound 9 (Scheme 5) was isol-
cause the hydroxy group at C(3) is unblocked and the acet- ated in 3% yield (entry 5).
als are acid sensitive. Unfortunately, all attempts to improve
the yield of 6 using a variety of thermodynamic acetaliz-
ation conditions failed. In all cases the ratio of 5 and 6
remained unchanged.
Scheme 4. Kinetic acetalization of quinic acid (2)
Scheme 3. Product ratio of the thermodynamic acetalization of
quinic acid (2)
Alternatively, acetalization of carbonyl compounds can
be effected under kinetic reaction conditions. In this case, a
Scheme 5. By-products of the kinetic acetalization in acetone and
ketone or aldehyde and an alkoxysilane were reacted at low
DMP, respectively
temperature with catalytic amounts of a Lewis acid.[15]
Silylation of (Ϫ)-quinic acid (2) with 5.5 equivalents of
trimethylsilyl chloride (TMS-Cl) and six equivalents of
The workup procedure strongly affected the yield of
Et3N (5 h, Ϫ5 °C) afforded the pentasilyl derivative 7 in product 6. Quenching of the reaction by addition of pyrid-
95% yield (Scheme 4). Next, silyl ether 7 and acetone (4 ine[15] gave varying yields of bisacetonide 6 (20Ϫ50%) under
equiv.) were treated with 11 mol-% of trimethylsilyl trifluor- otherwise similar conditions. More reproducible results
omethanesulfonate (TMS-OTf) at Ϫ75 °C for one hour and were obtained when the cold (Ϫ30 °C) or a re-cooled (Ϫ80
at Ϫ30 °C for 20 hours.[15a] Three products, quinide 5, bis- °C) reaction mixture was poured into a saturated solution
acetonide 6, and compound 8, derived from the addition of of NaHCO3 and the aqueous phase was immediately neut-
mesityloxide to 6, were obtained in 42, 50 and 5% yield, ralized with NH4Cl.
respectively (Scheme 4 and Table 1, entry 1). In order to
Taking into account that 8 is derived from 6, the yield
improve the yield of 6 various reaction parameters were va- of quinic acid bisacetonide was between 41 and 71%, and
Table 1. Optimization of the kinetic acetalization of silyl ether 7
Entry
Reagent
[equiv.]
Solvent
Lewis acid.
[mol-%]
T
[°C]
t
[h]
Workup[a]
6, 5, 8
[%][b]
1
2
acetone [4]
acetone [9]
acetone [9]
acetone [10]
acetone [87]
DMP [3]
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Ϫ
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Ϫ
TMS-OTf [11]
TMS-OTf [20]
TMS-OTf [20]
TMS-OTf [18]
TMS-OTf [18]
TMS-OTf [20]
TMS-OTf [16]
TMS-OTf [7]
TMS-OTf [15]
TMS-OTf [5]
BF3·Et2O [16]
TiCl4 [8]
Ϫ75 Ǟ Ϫ30
Ϫ75 Ǟ Ϫ30
Ϫ75
Ϫ95 Ǟ Ϫ30
Ϫ95 Ǟ Ϫ30
Ϫ75 Ǟ Ϫ30
Ϫ75
Ϫ75 Ǟ Ϫ30
Ϫ98 Ǟ Ϫ30
Ϫ30
Ϫ75 Ǟ Ϫ30
Ϫ75 Ǟ Ϫ30
Ϫ95 Ǟ Ϫ30
Ϫ95 Ǟ Ϫ30
1 Ǟ 16
4 Ǟ 16
2
2 Ǟ 70
2 Ǟ 70
6 Ǟ 16
24
2 Ǟ 70
2 Ǟ 55
4
1 Ǟ 30
1 Ǟ 71
2 Ǟ 24
2 Ǟ 5
A
A
A
B
B
C
C
C
B
C
C
C
B
B
50:42:5
50:19:18
36:10:5
3
4
48:39:10
48:21:23[c]
48:32:Ϫ
5:5:Ϫ
47:41:Ϫ
38:30:Ϫ[d]
20:Ϫ:Ϫ[e]
20:20:Ϫ
Ϫ:25:Ϫ
82:13:Ϫ[f]
74:6:Ϫ
5
6
7
DMP [3]
8
DMP [3]
9
DMP [3]
10
11
12
13
14
DMP [33]
DMP [9]
CH2Cl2
CH2Cl2
Ϫ
DMP [9]
acetone [36]/DMP [22]
acetone [58]/DMP [17]
TMS-OTf [18]
TMS-OTf [18]
Ϫ
[a]
A: pyridine was added, B: reaction cooled to Ϫ80 °C, added to a sat. NaHCO3 solution and neutralized with NH4Cl, C: poured at
Ϫ30 °C into a sat. NaHCO3 solution and neutralized with NH4Cl. Ϫ [b] Various amounts of TMS ethers 10 and 11 were formed especially
[c]
[d]
in cases when DMP was used as reagent. Ϫ Phorone adduct 9 was isolated in 3% yield. Ϫ About 20% of 10 and 11 were obtained.
Ϫ
Not determined. Ϫ [f]About 3% of 10 was isolated.
[e]
1138
Eur. J. Org. Chem. 2001, 1137Ϫ1141

First Efficient Synthesis of Chlorogenic Acid
FULL PAPER
suppression of compound 8 was therefore desirable. Acet- in 65% overall yield from 2 and in 51% overall yield from
one was therefore replaced by DMP as carbonyl synthon. 3 (based on 1.5 equivalents of 3 employed for the ester-
As expected, no mesityl adduct 8 was formed under a vari- ification reaction). The key intermediate was bisacetonide 6
ety of reaction conditions (entries 6Ϫ12), although DMP which was prepared as the major product (82%) for the first
had several disadvantages. In particular: (i) the yields of time using a kinetic acetalization protocol. By using this
compound 6 were generally lower than those achieved with strategy, isotope labeled chlorogenic acid derivatives should
acetone as reactant; (ii) the reaction mixture soon turned be obtained in high yields from the corresponding starting
deep red-brown after addition of the Lewis acid. The materials[7b,17]
brownish reaction product obtained after workup was diffi-
cult to purify because several by-products, derived from
DMP, were formed; (iii) cleavage of the remaining silyl ether
during the reaction was always incomplete, and silyl ether
Experimental Section
10 and 11 (Scheme 5) were generally isolated, each in
5Ϫ10% yield. Both silyl ethers 10 and 11 could be cleaved
quantitatively to 5 and 6, respectively, with tetrabutylam-
monium fluoride (TBAF) at Ϫ30 °C. The reaction temper-
ature was critical because quinide 5 was exclusively formed
from a 1:1 mixture of 10 and 11 when the reaction was
carried out at 0 °C. It was assumed that the lability of the
dioxolanone moiety of 6 was caused by a proximity of the
hydroxy group at C(3) and the carboxyl group at C(1) re-
sulting in a rapid cyclization to the lactone although the X-
ray crystal structure of 6 provided no evidence for this as-
sumption.[16]
As a consequence, a mixture of both carbonyl compon-
ents, DMP and acetone, gave the best yields of 6 (up to
82%) (Table 1, entries 13 and 14). No adduct 8 was formed
under these conditions and the amount of silyl ethers 10
and 11 was below 3%.
General Procedures: All reactions were performed in dried glass-
ware under an inert (N2) atmosphere. Standard reagents and solv-
ents were purified according to known procedures.[18] Thin layer
chromatographic (TLC) analyses were performed on silica gel
plates Merck 60 F254. Column chromatographic purifications
(‘‘flash chromatography’’, FC) were performed as described else-
where.[19] Melting points were determined using a Büchi SMP-20
apparatus and are uncorrected. Optical rotations were measured
with a JASCO DIP-1000 polarimeter. 1H NMR and 13C NMR
spectra were obtained using a Bruker ARX 300 instrument at 300.1
and 75.4 MHz, respectively. Unless otherwise stated, CDCl3 was
used as solvent. IR spectra were recorded with a PerkinϪElmer
FT-IR 16 PC instrument either from KBr plates or neat. UV spec-
tra were obtained from alcoholic solutions utilizing an ATI UN-
ICAM UV 3 instrument. Mass spectra were achieved by electron
impact (EI) using a Finnigan MAT SSQ 710 instrument and
MALDI-MS were recorded on a Bruker Reflex II (positive ion
mode, matrix: THAP). Elemental analyses were performed on a
LECO CHNS-932 instrument.
Esterification of 6 with 1.5 equivalents of 3 was realized
in dichloromethane at 0 °C under standard esterification Preparation of Acid Chloride 3: To a solution of caffeic acid (7.20 g,
40.0 mmol) and DMAP (0.12 g, 1.0 mmol) in pyridine (20 mL) was
acetic anhydride added (9.4 mL, 0.1 mol) at 0 °C. The reaction
mixture was stirred for 1 h and then poured onto crushed ice. The
aqueous phase was acidified with 2  aq. HCl (pH ഠ 2) and ex-
tracted with EtOAc/THF (3:1; 3 ϫ 80 mL). The combined organic
extracts were dried over MgSO4, filtered, and the solvents were
removed under reduced pressure. Trituration of the residue with
light petroleum containing small amounts of EtOAc afforded di-
O-acetylcaffeic acid (10.4 g, 39 mmol) as a colorless powder. This
was suspended in toluene (200 mL) containing five drops of DMF.
Oxalyl chloride (7.0 mL, 0.08 mol) was added at Ϫ5 °C. After stir-
ring for 3 h at room temperature, all starting material had dissolved
resulting in a pale-brown solution. Toluene and unreacted oxalyl
chloride were removed under reduced pressure. The residual brown-
ish product was recrystallized from toluene to afford 6.0 g of acide
chloride 3. The mother liquid was concentrated and the residue
triturated with light petroleum containing small amounts of
EtOAc. A total of 10.6 g (93%) of acid chloride 3 was obtained as
a pale yellow powder. Ϫ 1H NMR: δ ϭ 7.77 (d, J ϭ 15.5 Hz, 1 H),
7.46 (dd, J ϭ 8.4, 1.9 Hz, 1 H), 7.43 (d, J ϭ 1.9 Hz, 1 H), 7.28 (d,
J ϭ 8.4 Hz, 1 H), 6.49 (d, J ϭ 15.5 Hz, 1 H), 2.32 (s, 3 H), 2.31 (s,
3 H). Ϫ 13C NMR: δ ϭ 167.91 (s), 167.72 (s), 165.78 (s), 148.44
(d), 144.78 (s), 142.60 (s), 131.59 (s), 127.39 (d), 124.27 (d), 123.65
(d), 123.28 (d), 20.59 (q), 20.53 (q). Ϫ MS (70 eV): m/z (%) ϭ 284
(3), 282 (8), 247 (74), 242 (8), 240 (24), 205 (41), 200 (9), 198 (28),
163 (100).
Scheme 6. Final steps to chlorogenic acid (1)
conditions. Ester 12 was obtained in 92% yield (Scheme 6).
Cleavage of all protecting groups of ester 12 was achieved
with 1  aqueous HCl containing 15% THF. When 2  HCl
was used,[10] saponification of the caffeic ester was observed
to some extent (15%) whereas deprotection was very slow
with 0.5  HCl. The progress of the hydrolysis of the two
acetonides and of the two phenol acetates was monitored
by MALDI-TOF mass spectra. Hydrolysis of the protecting
groups was complete after 10 days at room temperature,
and chlorogenic acid (1) was isolated in 91% yield
(Scheme 6).
Conclusion
We have developed the first efficient synthesis of chloro-
genic acid (1) starting from caffeic and quinic acid. In only
Preparation of Bisacetonide 6: To a suspension of quinic acid 2
(2.00 g, 10.4 mmol; dried for 4 h, 30 °C, 5 ϫ 10Ϫ3 mbar) in CH2Cl2
four steps (three purifications), compound 1 was obtained (40 mL) was added Et3N (8.0 mL, 58 mmol) at Ϫ15 °C. The reac-
Eur. J. Org. Chem. 2001, 1137Ϫ1141 1139

M. Sefkow
FULL PAPER
tion mixture turned clear within a few minutes and trimethylsilyl
chloride (7.0 mL, 55 mol) was added at that temperature. A white
15.0 mmol) at room temperature. The reaction mixture was stirred
for 5 h and acidified with 1  aq. HCl (pH ഠ3). The layers were
precipitate was immediately formed. The suspension was stirred for separated and the aqueous phase re-extracted with CH2Cl2 (2 ϫ
4.5 h while the temperature was maintained below 0 °C. Pentane
(100 mL) was added and the precipitate was filtered off. The filter
cake was washed with hot pentane (2 ϫ 100 mL). The solvents were
removed under reduced pressure. The residue was redissolved in
pentane (200 mL) and any remaining traces of ammonium salt were
filtered off. Pentane was removed in vacuo to give silyl ether 7
(5.47 g, 95%) as a pale yellow liquid (in an attempt to purify 7 by
vacuum distillation, decomposition of 7 occurred).
50 mL). The combined organic extracts were dried (MgSO4), fil-
tered, and the solvents were removed in vacuo. The residue was
purified by FC (6 ϫ 30 cm, 30Ϫ40% EtOAc/light petroleum) to
afford 4.81 g (92%) of ester 12 as a colorless amorphous solid. M.p.
73Ϫ75 °C. Ϫ [α]2D3 ϭ Ϫ33.6 (c ϭ 1.0, CH2Cl2). Ϫ IR (KBr): ν˜ ϭ
2991, 1784, 1715, 1640, 1209, 1175 cmϪ1. Ϫ 1H NMR: δ ϭ 7.67
(d, J ϭ 16.0 Hz, 1 H), 7.40 (dd, J ϭ 8.3, 1.8 Hz, 1 H), 7.35 (d, J ϭ
1.8 Hz, 1 H), 7.22 (d, J ϭ 8.3 Hz, 1 H), 6.40 (d, J ϭ 16.0 Hz, 1 H),
5.27 (ddd, J ϭ 11.0, 7.2, 3.8 Hz, 1 H), 4.53 (dt, J ϭ 5.6, 3.8 Hz, 1
H), 4.21 (dd, J ϭ 7.2, 6.1 Hz, 1 H), 2.33Ϫ2.29 (m, 2 H), 2.31 (s, 3
H), 2.30 (s, 3 H), 2.25 (br. dd, J ϭ 13.6, 3.8 Hz, 1 H), 1.93 (dd,
J ϭ 13.6, 11.0 Hz, 1 H), 1.65 (s, 3 H), 1.63 (s, 3 H), 1.56 (s, 3 H),
1.38 (s, 3 H). Ϫ 13C NMR: δ ϭ 174.13 (s), 167.97 (s), 167.90 (s),
165.80 (s), 143.55 (s), 143.46 (d), 142.40 (s), 133.13 (s), 126.37 (d),
123.91 (d), 122.82 (d), 118.94 (d), 110.84 (s), 109.43 (s), 78.04 (s),
75.95 (d), 72.39 (d), 70.22 (d), 35.83 (t), 34.75 (t), 28.59 (q), 28.28
(q), 27.77 (q), 25.49 (s), 20.59 (q). Ϫ MS (70 eV): m/z (%) ϭ 519
(43), 503 (57), 476 (24), 461 (43), 434 (45), 418 (39), 376 (100), 318
(30), 254 (62), 247 (41). Ϫ UV (EtOH): λmax (ε) ϭ 281 (21000), 220
(14000) nm. Ϫ C26H30O11 (518.52): calcd. C 60.23, H 5.83; found
C 60.19, H 5.93.
A solution of 7 (5.14 g, 9.3 mmol) in acetone (25 mL) and DMP
(25 mL) was cooled to Ϫ95 °C and a solution of TMS-OTf
(0.3 mL, 1.7 mmol) in CH2Cl2 (3 mL) was added dropwise. The
reaction mixture was stirred for 2 h while warming to Ϫ45 °C. The
yellow solution was kept at Ϫ30 °C for 24 h, re-cooled to Ϫ80 °C
and added to a sat. aq. NaHCO3 solution (100 mL), whereupon
the color faded. The aqueous layer was extracted with EtOAc (3 ϫ
40 mL). The combined organic extracts were dried over MgSO4,
filtered, and the solvents were removed under reduced pressure.
Purification of the residue (SiO2, 6 ϫ 20 cm, 25Ϫ65% EtOAc/light
petroleum) afforded 0.30 g (13%) of quinide 5 and 2.10 g (82%) of
bisacetonide 6 as colorless crystals. M.p. 124 °C (ref.[14]: oil). Ϫ
[α]2D3 ϭ Ϫ27.0 (c ϭ 0.2, CH2Cl2). Ϫ IR (KBr): ν˜ ϭ 3501, 2993,
1
1779, 1291, 1218, 1051 cmϪ1. Ϫ H NMR: δ ϭ 4.48 (dt, J ϭ 5.5,
Preparation of Chlorogenic Acid (1): Ester 12 (1.56 g, 3.0 mmol)
was dissolved in a mixture of THF (20 mL) and aq. 1  HCl
(80 mL) at room temperature. The reaction mixture was stirred at
room temperature, and progress was monitored by MALDI-MS.
After 10 days, the solution was saturated with solid NaCl and the
aqueous phase extracted with EtOAc (3 ϫ 30 mL). The combined
organic phases were dried (MgSO4), filtered, and the solvents were
removed in vacuo. The crystalline residue was triturated with hot
Et2O to afford 0.75 g (70%) of chlorogenic acid (1). The mother
liquid was concentrated and the trituration step was repeated. An
additional 0.22 g (21%) of 1 was obtained. All analytical data of
synthetic 1 were in agreement with those obtained from purchased
chlorogenic acid (Merck).
4.3 Hz, 1 H), 4.05Ϫ3.98 (m, 2 H), 2.88 (br. s, 1 H), 2.31 (dd, J ϭ
15.3, 4.7 Hz, 1 H), 2.20 (br. dd, J ϭ 15.3, 3.9 Hz, 1 H), 2.13 (br. d,
J ϭ 13.9 Hz, 1 H). Ϫ 1.94 (dd, J ϭ 13.9, 9.3 Hz, 1 H), 1.62 (s, 3
H), 1.61 (s, 3 H), 1.52 (s, 3 H), 1.37 (s, 3 H). Ϫ 13C NMR: δ ϭ
176.10 (s), 111.43 (s), 108.97 (s), 78.34 (s), 78.22 (d), 71.69 (d),
67.46 (d), 37.26 (t), 34.95 (t), 28.52 (q), 27.79 (q), 25.25 (q). Ϫ MS
(70 eV): m/z (%) ϭ 271 (13), 257 (100), 43 (50). Ϫ C13H20O6
(272.30): calcd. C 54.34, H 7.40; found C 54.31, H 7.61.
By using pure acetone instead of acetone/DMP as solvent, com-
pounds 5 (21%),[14] 6 (48%), 8 (23%) and 9 (3%) were isolated.
Compound 8: M.p. 76 °C. Ϫ [α]2D3 ϭ Ϫ61.5 (c ϭ 1.0, CH2Cl2). Ϫ
IR (KBr): ν˜ ϭ 2981, 1790, 1711, 1369, 1273, 1224, 1034 cmϪ1. Ϫ
1H NMR: δ ϭ 4.45 (dt, J ϭ 5.0, 4.0 Hz, 1 H), 3.95Ϫ3.84 (m, 2 H),
2.68/2.58 (AB, J ϭ 13.9 Hz, 2 H), 2.24 (dd, J ϭ 15.4, 4.9 Hz, 1 H),
2.20 (s, 3 H), 2.15 (ddd, J ϭ 15.5, 3.7, 1.8 Hz, 1 H), 1.94 (ddd, J ϭ
13.8, 3.7, 1.7 Hz, 1 H), 1.78 (dd, J ϭ 13.8, 10.6 Hz, 1 H), 1.60 (s,
3 H), 1.59 (s, 3 H), 1.53 (s, 3 H), 1.36 (s, 3 H), 1.32 (s, 3 H), 1.27
(s, 3 H). Ϫ 13C NMR: δ ϭ 208.14 (s), 174.39 (s), 110.32 (s), 108.62
(s), 78.57 (s), 78.53 (d), 75.69 (s), 72.62 (d), 67.78 (d), 55.43 (t),
39.42 (t), 35.04 (t), 32.48 (q), 28.58 (q), 28.41 (q), 27.94 (q), 26.21
(q), 26.07 (q), 25.48 (q). Ϫ MS (70 eV): m/z (%) ϭ 371 (36), 313
(13), 273 (74), 254 (100). Ϫ C19H30O7 (370.45): calcd. C 61.60, H
8.16; found C 61.62, H 8.40.
Acknowledgments
This work was supported by Prof. M. G. Peter and by the Fonds
der Chemischen Industrie. The Deutsche Forschungsgemeinschaft
is acknowledged for a habilitation grant (Se 875/1Ϫ1). Thanks also
go to Mrs. C. -M. Matern for extensive experimentation, to Dr. S.
Haebel for recording of the MALDI-MS spectra, and to Dr. D.
Schanzenbach for critical comments to the manuscript.
[1]
M. N. Clifford, J. Sci. Food Agric. 1999, 79, 362Ϫ372.
P. A. Kroon, G. Williamson, J. Sci. Food Agric. 1999, 79,
355Ϫ361.
Phytochemical Dictionary (Eds.: J. B. Harborne, H. Baxter),
Taylor & Francis, London, 1993, 1745.
[2]
Compound 9: 1H NMR: δ ϭ 6.19 (s, 1 H), 4.45 (dt, J ϭ 5.0, 3.7 Hz,
1 H), 3.96Ϫ3.85 (m, 2 H), 2.66/2.60 (AB, J ϭ 13.5 Hz, 2 H), 2.25
(dd, J ϭ 15.3, 4.9 Hz, 1 H), 2.14 (ddd, J ϭ 15.3, 2.7, 1.2 Hz, 1 H),
2.12 (s, 3 H), 1.95 (ddd, J ϭ 13.9, 3.6, 1.3 Hz, 1 H), 1.87 (s, 3 H),
1.78 (dd, J ϭ 13.9, 10.6 Hz, 1 H), 1.60 (s, 3 H), 1.59 (s, 3 H), 1.53
(s, 3 H), 1.35 (s, 3 H), 1.32 (s, 3 H), 1.28 (s, 3 H). Ϫ 13C NMR:
δ ϭ 199.42 (s), 174.39 (s), 154.20 (s), 125.77 (d), 110.17 (s), 108.50
(s), 78.48 (s), 78.43 (d), 76.04 (s), 72.53 (d), 67.50 (d), 55.74 (t),
39.28 (t), 34.95 (t), 28.52 (q), 28.34 (q), 27.84 (q), 27.56 (q), 26.31
(q), 26.18 (q), 25.38 (q), 20.54 (q).
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1140
Eur. J. Org. Chem. 2001, 1137Ϫ1141

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Received September 21, 2000
[O00437]
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Eur. J. Org. Chem. 2001, 1137Ϫ1141
1141