Synthesis of new biosynthetically important diarylheptanoids and their oxa- and fluoro-analogues by three different strategies

Article abstract of DOI:10.1081/SCC-120016367

Wittig, aldol and Wittig-Horner reactions have been used to synthesize new diarylheptanoids, which are putative intermediates in phenylphenalenone biosynthesis in plants. The Wittig-Horner approach was most suitable and gave significantly higher yields in comparison with other methods.

Full text of DOI:10.1081/SCC-120016367

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Synthesis of New Biosynthetically Important
Diarylheptanoids and Their Oxa- and Fluoro- Analogues
by Three Different Strategies
Alexander Baranovsky a b , Bettina Schmitt a c , Daniel J. Fowler a & Bernd Schneider a
a Max-Planck Institute for Chemical Ecology, Jena, Germany
b Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
c Combinature Biopharm AG, Berlin, Germany
Published online: 17 Aug 2006.
To cite this article: Alexander Baranovsky , Bettina Schmitt , Daniel J. Fowler & Bernd Schneider (2003): Synthesis of New
Biosynthetically Important Diarylheptanoids and Their Oxa- and Fluoro- Analogues by Three Different Strategies, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:6, 1019-1045
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 6, pp. 1019–1045, 2003
Synthesis of New Biosynthetically Important
Diarylheptanoids and Their Oxa- and Fluoro-
Analogues by Three Different Strategies
Alexander Baranovsky,# Bettina Schmitt,y Daniel J. Fowler,
*
and Bernd Schneider
Max-Planck Institute for Chemical Ecology, Jena,
Germany
ABSTRACT
Wittig, aldol and Wittig-Horner reactions have been used to synthe-
size new diarylheptanoids, which are putative intermediates in
phenylphenalenone biosynthesis in plants. The Wittig-Horner
approach was most suitable and gave significantly higher yields in
comparison with other methods.
#Current address: Institute of Bioorganic Chemistry, National Academy of
Sciences of Belarus, Minsk, Belarus.
yCurrent address: Combinature Biopharm AG, Berlin, Germany.
*
Correspondence: Bernd Schneider, Max-Planck Institute for Chemical
Ecology, Beutenberg Campus, Winzerlaer Str. 10, 07745 Jena, Germany;
Fax: þ49-3641-571601; E-mail: schneider@ice.mpg.de.
1019
DOI: 10.1081/SCC-120016367
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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1020
Baranovsky et al.
Key Words: Diarylheptanoids; Aldol reaction; Wittig reaction;
Wittig-Horner reaction.
1. INTRODUCTION
Diarylheptanoids represent a group of natural products occurring in
various monocot and dicot plant species.[1,2] The Zingiberaceae plant
family is an especially rich source of diarylheptanoids. Curcumin, the
most well-known diarylheptanoid, is a major spice and pigment principle
of Curcuma longa (Zingiberaceae) and other Curcuma species. In bioas-
says it exhibits strong antioxidant and chemopreventive activities.[3,4]
Diarylheptanoids of the Zingiberaceae structurally related to curcumin
are also referred to as curcuminoids. Compounds of that type are
considered intermediates in the biosynthesis of cyclic phenolic natural
products, the phenylphenalenones, which represent characteristic
constituents of the Haemodoraceae and Musaceae plant families.
Involvement of diarylheptanoids in phenylphenalenone biosynthesis has
been confirmed by feeding experiments using a labelled precursor of that
type.[5] More detailed studies to establish the occurrence of and exact
biosynthetic pathway to phenylphenalenones require synthesis of
diarylheptanoids as analytical standards and putative intermediates.
As putative intermediates of phenylphenalenone biosynthesis, diaryl-
hepta-4,6-dien-3-ones are of special interest. In the original synthesis of
diarylheptadienones, the Wittig reaction was used as the central step.[6,7]
Since then many approaches to related diaryl dienones and other diaryl-
heptanoids have been elaborated[8,9] mainly based on the aldol condensa-
tion[10–12] and the Wittig-Horner reaction.[13,14] We herein describe the
synthesis of new (E,E)-diarylhepta-4,6-dien-3-ones, which were prepared
via three different approaches: Wittig reaction following the procedure of
Sakakibara et al.,[6] aldol condensation, and Wittig-Horner reaction.
2. RESULTS AND DISCUSSION
2.1. Wittig Approach
The procedure described for the synthesis of 4,6-heptadien-3-ones[6,7]
was found rather laborious and, in the case of phenolic compounds, gave
low yields. It starts from a phenylpropionic acid e.g., hydrocaffeic acid
(1), which after protection was treated subsequently with thionyl chlor-
ide, diazomethane, HBr, and triphenylphosphine. In the final step,

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Diarylheptanoids
1021
Scheme 1. Reagents and conditions: i: Ac2O, Py, r.t., 8 h, 87 % for 2 and 75 %
for 9; ii: (COCl)2, benzene, reflux, 45 min; iii: 1) CH2N2, benzene, 8ꢀC, 30 min, 2)
r.t., 2 h; iv: HBr (48%), benzene, 5ꢀC, 30 min, 48% based on 2; v: P (CH5)3,
6
benzene, r.t., 48 h, 80%; vi: 1) K2CO3, H2O, 80ꢀC, 10 min, 2) 7 or 9, benzene,
reflux, 48 h, 48% for 10 and 46% for 11 based on 6; vii: MeONa, MeOH, r.t.,
10 min, 82% for 12 and 76% for 13.
the phosphonium salt 6 was reacted with aldehyde 7 and 9, respectively
(Sch. 1).[15] Two low-yield steps, the bromination (48%) and the Wittig
reaction (48% for 10 and 45% for 11) diminished total yield of com-
pounds 12 and 13 to only 13% and 11% respectively.
2.2. Aldol Condensation
As a result of the low total yields of the diarylheptanoids obtained by
the Wittig approach, further strategies were pursued. The synthesis of
dienone 14 was started from the commercially available ketone 15. The
phenolic hydroxyl group was protected as the benzoate ester because this
protection group does not interfere with preparation of a ketone enolate
with LDA and is furthermore advantegeous by the ease of removal by
treatment with mild base.[16] The protected ketone 16 was treated with

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1022
Baranovsky et al.
Scheme 2. Reagents and conditions: i: BzCl, Py, DMAP, DCM, r.t., 12 h, 90%;
ii: 1) LDA, THF, ꢁ78ꢀC, 2) cinnamic aldehyde, 3) TMSCl, THF, r.t., 1 h, 40%;
iii: K2CO3, MeOH, r.t., 2 h, 49% from 17, 65% from 19; iv: 1) LDA, THF,
ꢁ78ꢀC, 2) cinnamic aldehyde, 63%; v: TsOH(cat), C6H6, reflux, 10 min, 99%.
LDA at low temperature and the resulting enolate was reacted with
cinnamic aldehyde (Sch. 2). Reports had shown that the addition of
TMSCl to the reaction mixture drastically improved yields of die-
nones.[17,18] However, in our case, analysis of the reaction mixture
showed a very slow formation of dienone from the TMS-ether 17.
Finally, the reaction was quenched and 17 was isolated in 40% yield
after chromatography. Treatment of TMS-ether 17 with K2CO3 in
methanol effected hydrolysis of protection group and subsequent dehy-
dration to give 14. Unfortunately, the reaction was accompanied by for-
mation of the retroaldol product, which reduced the yield of the desired
diarylheptanoid 14 to 49%. The aldol reaction was repeated without
adding TMSCl, and the intermediate product 18 was dehydrated with
TsOH, which resulted in a greater yield. The overall yield of 14 from
three steps (addition, dehydration and hydrolysis) was substantially
better (40%) than in the first procedure (19% for two steps).
The starting material for the synthesis of dienone 12 was prepared in
a two-step procedure from 3,4-dihydroxybenzaldehyde 20 (Sch. 3).
Knoevenagel condensation with piperidinium acetate as a catalyst[18,19]
gave ketone 21 and avoided the need for protection of the hydroxy
groups. There are no reports on chemoselective hydrogenation of

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Diarylheptanoids
1023
Scheme 3. Reagents and conditions: i: Me2CO, MeCN, AcOH, C5H10NH, reflux,
4 h, 48%; ii: HCO2NH4, Pd/C, Me2CO, MeOH, r.t., 1 h, 90%; iii: EtOCH¼CH2,
Et2O, r.t., 24 h, 95%; iv: 1) LDA, THF, ꢁ78ꢀC, 2) cinnamic aldehyde, 3)
TsOH(cat), MeOH, r.t., 5 min, 4) TsOH, THF, C6H6, r.t., 48 h, 38%; v: 1)
LDA, THF, ꢁ78ꢀC, 2) cinnamic aldehyde, TMSCl, 3) DBU, THF, reflux, 3 h,
44 %; vi: TsOH(cat), MeOH, r.t., 5 min, 96%.
double bond in the unprotected ketone 21. Transfer hydrogenation of 21
with ammonium formate was performed in order to simplify the proce-
dure and to avoid the use of hydrogen gas. The problem of excessive
reduction resulting in the saturated alcohol, which heavily diminished the
yield of the desired ketone,[20,21] was avoided by adding acetone to reac-
tion mixture.[22,23] The ketone 22 was obtained in 90% yield.
Subsequent steps required the selection of a protecting group for the
catechol moiety. It is known[5] that the final compound 12 is rather
unstable and would not withstand the harsh conditions used for depro-
tection of typical protection groups in catechols.[16] On the other hand,
the protection group had to be stable during the aldol reaction and
purification. The ethoxyethyl group (EE) was chosen, because this pro-
tection group fulfills the above requirements, gives good yields, and does
not hinder the reaction site. The drawback is the introduction of two
chiral centers into the molecule, which generates two diastereomers
that complicate the interpretation of NMR spectra to some extent.
Thus, ketone 22 was protected as EE ether 23, and the latter was used
in the aldol reaction. However, we obtained very modest yields (38–44%)

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1024
Baranovsky et al.
of compound 12 in the elimination step under both basic (DBU) and
acidic (TsOH) conditions. Again, the major concurrent reaction was
the retroaldol process.
Oxa-analogues of diarylheptanoids (e.g., 2-hydroxy-5-phenylpenta-
noic acid benzyl ester) are accessible by enantioselective aldol addition
using benzyl acetate derived silyl ketene acetal.[24] In our case enantios-
electivity was not necessary because dehydration resulted in the subse-
quent loss of stereochemistry. Accordingly, the oxa-analogue of
diarylheptanoid 12 was synthesized by means of an aldol-type condensa-
tion of cinnamic aldehyde with protected acetic acid 3,4-dihydroxybenzyl
ester. The procedure started with 3,4-dioxybenzaldehyde 20, which was
protected as the EE-ether 25[25] and reduced with NaBH4. The obtained
alcohol 26 was acetylated to give acetate 27. These steps gave almost
quantitative yields and did not require additional purification. The reac-
tion of cinnamic aldehyde 7 with the anion of ester 27 led to hydroxy
ester 28 in a good yield (81%). The dehydration step was carried out in
the presence of acetic anhydride and DBU and the dienonate 29 was
1
isolated in 74% yield. The H NMR spectrum revealed a minor admix-
ture of cis-isomer of compound 29. The deprotected dienoate 30 (Sch. 4)
was extremely labile under acidic and basic conditions due to its benzylic
nature and in order to obtain compound 30 in high yields, compound 29
was treated with TsOH and the reaction quenched with pyridine to
ensure neutral conditions during the work up.
Scheme 4. Reagents and conditions: i: EtOCH¼CH2, Et2O, r.t., 3d, 91%; ii:
NaBH4, CH2Cl2–MeOH, ꢁ5ꢀC, 0.5 h, 99%; iii: Ac2O, Py, CH2Cl2, r.t., 1 h,
99%; iv: 1) LDA, THF, ꢁ78ꢀC, 2) cinnamic aldehyde, 0.5 h, 81%; v: Ac2O,
DBU, C6H6, 90ꢀC, 2.5 h, 74%; vi: TsOH(cat), MeOH, r.t., 5 min, 99%.

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Diarylheptanoids
1025
2.3. Wittig-Horner Approach
Having such low yields, we reconsidered our approach and decided
to use the Wittig-Horner reaction. The starting material for the synthesis,
ester 32, was prepared from hydrocaffeic acid (1) in 92% yield. As
expected, the transformation of ester 32 into phosphonate 33 after pur-
ification gave the product in 87% yield (11% of starting material was
recovered). Phosphonate 33 was used under conditions of the Wittig-
Horner reaction proposed in the synthesis of shogaol[26] (Sch. 5).
However, the use of NaH as a base resulted in moderate yields of the
product, which were compatible with yields of the aldol reaction.
Conditions[13,27,28,29] employing LiCl and an organic base were also unsa-
tisfactory, as the dienone was contaminated with low-molecular weight
byproducts. When the latter reaction was performed with only DBU as a
base, the desired compound 24 was isolated in 71% yield. Deprotection
was accomplished without complication to give dienone 12 in 96%. The
overall yield in the latter procedure over five steps, using DBU in the
condensation, was 54%.
It was desirable to synthesise a fluorine containing analogue of 12 and
13 for use in biosynthesis studies. In order to minimise the stereoelectronic
Scheme 5. Reagents and conditions: i: AcCl, MeOH, r.t., 12 h, 99%; ii:
EtOCH¼CH2, Et2O, r.t., 24 h, 92%; iii: 1) MeP(O)(OMe)2, THF, ꢁ78ꢀC, 2)
MeLi 3) 32, 1 h, 87%; iv: 1) NaH, THF, 0ꢀC, 2) 7, reflux, 3 h, 43%; v: DBU, 7
or 34, THF, reflux, 4 h, 71% for 24 and 44% for 36; vi: TsOH(cat), MeOH, r.t.,
5 min, 96% for 12.

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1026
Baranovsky et al.
pertubation caused by the introduction of fluorine, the 400-hydroxyl group
of 13 was substituted for fluorine. As the Wittig-Horner approach to
synthesize gave better yields compared with the Wittig synthesis and
aldol reaction, this method was chosen for the synthesis of the fluoro-
analogue of 13. The starting material, 3-(4-fluorophenyl)-2-propenal
(34), was prepared from p-fluorobenzaldehyde and acetaldehyde by
aldol condensation.[30] The product was purified via preparative TLC.
Condensation of the aldehyde 34 with phosphonate 33 and deprotection
in a one-pot process without isolation of the ethoxyethyl derivative 35
gave the fluorodiarylheptanoid (36) as the free catechol.
3. CONCLUSIONS
The synthesis of diarylheptanoids and analogues has been achieved
by three different strategies. The improved Wittig-Horner approach
proved the most suitable scheme for synthesis of (E,E)-diaryl-4,6-hepta-
dien-3-ones. A total yield of 54% in five steps was obtained compared
with 40% (from 22) in the aldol and approximately 12% in the Wittig
approach. Owing to the high overall yield, the proposed Wittig-Horner
approach is also suitable for syntheses of diarylhepta-4,6-dien-3-ones and
further diarylheptanoids in labelled form. Compound 12 and new diaryl-
heptanoids 13 and 14 have been suggested as biosynthetic intermediates
of phenylphenalenone biosynthesis, which after o-hydroxylation of the
phenolic ring (compound 14) and oxidation to o-quinones may represent
substrates for intramolecular Diels-Alder reaction.
4. EXPERIMENTAL SECTION
4.1. General Methods
Melting points were measured in a Buchi B-540 apparatus and are
uncorrected. Infrared spectra were recorded on a FTIR, Bruker
EQUINOX 55 spectrometer and only characteristic absorptions are
reported. NMR spectra were recorded on a Bruker DRX 500 spectro-
meter at 500.13 MHz (1H) and 125.75 MHz (13C), respectively, using
standard Bruker software. TMS was used as internal standard.
1H NMR, 1H–1H COSY, HMBC, and HMQC experiments were
recorded in a 2.5 mm inverse detection microprobe head. Broadband
decoupled 13C and DEPT spectra were run using a 2.5 mm broadband
microprobe head. Chemical shifts are reported in ꢀ values and coupling

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Diarylheptanoids
1027
constants are in Hz. MS and HRMS data were obtained with a
Micromass MasSpec mass spectrometer (70 eV). The ratio m/z and rela-
tive intensities (%) are indicated for the significant peaks. Column chro-
matography was performed on Merck silica gel 60 (0.04–0.2 mm).
Solvents were dried and freshly distilled according to common practice.
All reactions were carried out under positive nitrogen pressure. Reactions
were monitored by TLC on precoated silica gel 60 F-254 plates (Merck),
and visualization of the compounds was accomplished by UV light
and/or spraying with FeCl3 solution.
4.2. Wittig Synthesis
4.2.1. (E)-Acetoxycinnamaldehyde (9)
Compound 9 was synthesized from p-cumaraldehyde (8) by standard
acetylation procedure using acetic anhydride in pyridine. 1H NMR (acet-
one-d6): ꢀ 2.28 (3H, s, AcO), 6.75 (1H, dd, J ¼ 16.4, 7.6 Hz, H-2), 7.24
(2H, d, J ¼ 8.8 Hz, H-30 and H-50), 7.68 (1H, d, J ¼ 16.4 Hz, H-3), 7.76
(2H, d, J ¼ 8.8 Hz, H-20 and H-60), 9.71 (1H, d, J ¼ 7.6 Hz, H-1); EIMS:
m/z 190 (Mþ, 26), 148 (100), 131 (29), 120 (50).
4.2.2. (4E,6E)-1-(3,4-Diacetoxyphenyl)-7-(4-Acetoxyphenyl)-
Hepta-4,6-dien-3-one (11)
The Wittig reaction of the phosphonium bromide 6 with aldehyde 7
and 9, respectively, was performed using the procedure of Bazan et al.[7]
Phosphoniumbromide 6 (0.112 g, 0.185 mmol) was dissolved in hot
water (1.5 mL), and 0.5 mL of an aqueous solution of K2CO3 (0.027 g,
0.2 mmol) were added dropwise with stirring. The precipitated phosho-
nium ylide was separated, dissolved in benzene, dried by azeotropic
evaporation, and redissolved in dry benzene. Acetoxy-trans-cinnamalde-
hyde (9) (0.034 g, 0.19 mmol) was added, and the mixture was refluxed
for 48 h. The red solution was evaporated, and after chromatography
on a silica gel column with hexane-acetone 6:1 as eluent, gave 0.037 g
(46%) compound 11, M.p. 127–129ꢀC. IR (KBr): (ꢁmax cmꢁ1) 2982, 1782,
1
1764, 1681, 1593, 1505, 1371, 1218, 1006, 886, 839; H NMR (CDCl3): ꢀ
2.27 (3H, s, AcO), 2.28 (3H, s, AcO), 2.30 (3H, s, AcO), 2.92 (2H,
t, J ¼ 7.0 Hz, H-2), 2.97 (2H, t, J ¼ 7.0 Hz, H-1), 6.26 (1H,
d, J ¼ 15.4 Hz, H-4), 6.81 (1H, d, J ¼ 15.4, 10.8 Hz, H-6), 6.92

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Baranovsky et al.
(1H, d, J ¼ 15.4 Hz, H-7), 7.05 (1H, d, J ¼ 1.5 Hz, H-20), 7.09 (m, H-50, H-
60, H-300 and H-500), 7.30 (1H, dd, J ¼ 15.4, 10.8 Hz, H-5), 7.47 (2H, d,
J ¼ 8.5 Hz, H-200 and H-600); 13C NMR (CDCl3): ꢀ 20.6 (CH3CO), 20.6
(CH3CO), 21.1 (CH3CO), 29.4 (C-1), 41.9 (C-2), 122.0 (C-300 and C-500),
123.3 (C-20 and C-50), 126.6 and 126.8 (C-6 and C-60), 128.3 (C-200 and C-
600), 129.5 (C-4), 140.2 (C-10), 134.9 (C-100), 140.3 (C-40), 140.4 (C-7),
141.9 (C-30), 142.7 (C-5), 151.3 (C-400), 168.3 (CH3CO), 168.4 (CH3CO),
169.2 (CH3CO),198.8 (C-3); EIMS: m/z 436 (Mþ, 31), 393 (69), 352
(54), 310 (39), 187 (60), 173 (100). HRMS: Calcd. for C25H24O7:
436.1522, Found: 436.1518.
4.2.3. (4E,6E)-1-(3,4-Dihydroxyphenyl)-7-Phenylhepta-4,6-
dien-3-one (12)
Compound 12 was prepared from dihydrocaffeic acid (1) as described
by Bazan et al.[7] For analytical data, see 4.3.12. The intermediate
phosphonium bromide 6 was also used for the preparation of (4E,6E)-
1-(3,4-hydroxyphenyl)-7-(4-hydroxyphenyl)-hepta-4,6-dien-3-one (13).
4.2.4. (4E,6E)-1-(3,4-Dihydroxyphenyl)-7-(4-Hydroxyphenyl)-
Hepta-4,6-dien-3-one (13)
For deprotection, 120 mL of 1 M solution of NaOMe in abs.
MeOH were added dropwise within 5 min to a stirred solution
of compound 11 (0.037 g, 0.085 mmol) in abs. MeOH (1 mL). The mixture
turned deep red and was stirred for another 5 min. Water (1 mL)
was added and after 5 min the alkaline mixture was acidified to pH 5.5
by the dropwise addition of 0.5 M HCl. The solution was extracted
with CHCl3 and purified by preparative TLC (CHCl3:MeOH 19:1).
1H NMR (acetone-d6): ꢀ 2.76 (2H, t, J ¼ 7.9 Hz, H-1), 2.86 (2H,
t, J ¼ 7.9 Hz, H-2), 6.25 (1H, d, J ¼ 15.5 Hz, H-4), 6.57 (1H, dd, J ¼ 8.0,
2.1 Hz, H-60), 6.72 (1H, d, J ¼ 8.0 Hz, H-50), 6.73 (1H, d, J ¼ 2.1 Hz, H-20),
6.86 (2H, d, J ¼ 8.8 Hz, H-300 and H-500), 6.89 (1H, dd, J ¼ 15.5, 10.5 Hz,
H-6), 7.01 (1H, d, J ¼ 15.5 Hz, H-7), 7.38 (1H, dd, J ¼ 15.5, 10.5 Hz, H-5),
7.44 (2H, d, J ¼ 8.8 Hz, H-200 and H-600); 13C NMR (acetone-d6): ꢀ 30.3
(C-1), 42.8 (C-2), 115.9 (C-50), 116.3 (C-20), 116.6 (C-300 and C-500), 120.4
(C-60), 125.0 (C-6), 129.0 (C-100), 129.3 (C-4), 129.8 (C-200 and C-600), 134.2
(C-10), 142.2 (C-7), 143.7 (C-40), 144.1 (C-5), 145.8 (C-30), 159.5 (C-400),
199.4 (C-3); EIMS: m/z 310 (Mþ, 92), 173 (100). HRMS: Calcd.
for C25H24O7: 310.1207, Found: 310.1205.

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Diarylheptanoids
1029
4.3. Aldol Condensation
4.3.1. 4-(4-Benzoyloxyphenyl)-Butan-2-one (16)
A solution of ketone 15 (0.98 g, 6 mmol), benzoyl chloride (0.77 mL,
6.6 mmol), pyridine (1.06 mL, 13.2 mmol) and DMAP(0.09 g, 0.7 mmol)
in CH2Cl2 (30 mL) was stirred at room temperature. After 4 h the solu-
tion was diluted with CH2Cl2, washed with water, brine, dried over
Na2SO4 and evaporated to yield the product (2.0 g). The crude product
was crystallized from EtOAc-hexane to give the protected ketone 16
(1.46 g, 90%), M.p. 72.3–72.7ꢀC. IR (KBr): (ꢁmax cmꢁ1) 2945, 2918,
1
1729, 1702, 1600, 1272, 1057, 883; H NMR (CDCl3): ꢀ 2.14 (3H, s, H-
1), 2.76 (2H, t, J ¼ 7.6 Hz, H-3), 2.90 (2H, t, J ¼ 7.6 Hz, H-4), 7.11 (2H, d,
J ¼ 8.2 Hz, H-30 and H-50), 7.22 (2H, d, J ¼ 8.2 Hz, H-20 and H-60), 7.49
(2H, m, H-300 and H-500), 7.61 (1H, t, J ¼ 7.5 Hz, H-400), 8.18 (2H, d,
J ¼ 7.9 Hz, H-200 and H-600); 13C NMR (CDCl3): ꢀ 29.1 (C-4), 30.1 (C-
1), 45.1 (C-3), 121.7 (C-30 and C-50), 128.5 (C-300 and C-500), 129.3 (C-20
and C-60), 129.5 (C-10), 130.1 (C-200 and C-600), 133.5 (C-400), 138.6 (C-100),
149.2 (C-40), 165.3 (COO), 207.7 (C-2); EIMS: m/z 268 (Mþ, 19), HRMS:
Calcd. for C17H16O3: 268.1099, Found: 268.1099.
4.3.2. (6E)-1-(4-Benzoyloxyphenyl)-7-Phenyl-5-
trimethylsilyloxy-hept-6-en-3-one (17)
To a stirred solution of LDA (1.6 mmol) in THF (5 mL) at ꢁ78ꢀC
was added a solution of ketone 16 (0.295 g, 1.1 mmol) in THF (5 mL) via
syringe. After 15 min, cinnamic aldehyde (0.138 mL, 1.05 mmol) in THF
(5 mL) was added. The mixture was stirred for 30 min at the indicated
temperature and TMSCl (0.265 mL, 2 mmol) was added in one portion.
The cooling bath was removed and the solution was allowed to warm
to ambient temperature. After 4 h, saturated NaHCO3 was added and the
mixture was extracted with EtOAc. The organic phase was washed with
brine, dried, and evaporated. The obtained residue was separated
on a silica gel column with CH2Cl2:hexane as eluent to yield TMS-
ether 17 as a pale yellow oil (0.188 g, 40%). IR (neat): (ꢁmax cmꢁ1
)
3027, 2953, 1736, 1714, 1600, 1264, 1058, 841; 1H NMR (CDCl3): ꢀ
0.12 (9H, s, CH3Si), 2.54 (1H, dd, J ¼ 4.8, 15.1 Hz, H-4a), 2.80 (3H, m,
H-4b and H-2), 2.92 (2H, t, J ¼ 7.7 Hz, H-1), 4.81 (1H, m, H-5), 6.17 (1H,
dd, J ¼ 6.4, 15.7 Hz, H-6), 6.55 (1H, d, J ¼ 15.7 Hz, H-7), 7.11 (2H, d,
J ¼ 8.5 Hz, H-30 and H-50), 7.23 (2H, d, J ¼ 8.5 Hz, H-20 and H-60),
7.25 (1H, tt, J ¼ 7.7, 1.3 Hz, H-400), 7.31 (2H, dd, J ¼ 7.7, 7.7 Hz, H-300

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1030
Baranovsky et al.
and H-500), 7.36 (2H, d, J ¼ 7.7 Hz, H-200 and H-600), 7.51 (2H, dd, J ¼ 7.7,
8.1 Hz, H-3000and H-5000), 7.62 (1H, tt, J ¼ 7.4, 1.3 Hz, H-4000), 8.18 (2H,
d, J ¼ 8.1 Hz, H-2000 and H-6000); 13C NMR (CDCl3): ꢀ 0.2 (CH3Si), 28.8
(C-1), 46.1 (C-2), 51.1 (C-4), 70.2 (C-5), 121.6 (C-30 and C-50), 126.5 (C-
200 and C-600), 127.6 (C-400), 128.5 (C-3000 and C-5000), 128.6 (C-300 and C-
500), 129.3 (C-20 and C-60), 129.6 (C-10), 129.7 (C-7), 130.1 (C-2000
and C-6000), 131.7 (C-6), 133.5 (C-4000), 136.6 (C-100), 138.7 (C-1000), 149.2
(C-40), 165.3 (COO), 207.8 (C-3); EIMS: m/z 472 (Mþ, 30), 447
(10), 382 (10), 367 (15), 325 (15), 261 (20), 247 (20), 205 (80).
HRMS: Calcd. for C29H32O4Si: 472.2070, Found: 472.2074.
4.3.3. (6E)-1-(4-Benzoyloxyphenyl)-5-Hydroxy-7-
phenylhept-6-en-3-one (18)
To a stirred solution of LDA (1.57 mmol) in THF (5 mL) at ꢁ78ꢀC
was added a solution of ketone 16 (0.35 g, 1.32 mmol) in THF
(5 mL) via a syringe. After 15 min, cinnamic aldehyde (0.17 mL,
1.31 mmol) in THF (5 mL) was added. The mixture was
stirred for 20 min at the indicated temperature and the reaction
was quenched with saturated NH4Cl. The solution was allowed
to warm to ambient temperature and then extracted with EtOAc. The
organic
phase
was
washed
with
brine,
dried,
and
evaporated. The obtained residue was purified on a silica gel
column with EtOAc:hexane as eluent to give 0.33 g (63%) of ketol
18, M.p. (hexane-ether) 74.2–75.0ꢀC. IR (KBr): (ꢁmax cmꢁ1) 3446, 3035,
2933, 1736, 1690, 1288, 1061, 960; 1H NMR (acetone-d6): ꢀ 2.70 (2H, dd,
J ¼ 15.6, 4.8 Hz, H-4a), 2.76 (2H, dd, J ¼ 15.6, 8.1 Hz, H-4b), 2.91 (4H, s,
H-1 and H-2), 4.77 (1H, m, H-5), 6.34 (1H, dd, J ¼ 15.9, 5.7 Hz, H-6),
6.65 (1H, dd, J ¼ 15.9, 1.3 Hz, H-7), 7.17 (2H, d, J ¼ 8.6 Hz, H-30 and H-
50), 7.23 (1H, tt, J ¼ 7.3, 1.3 Hz, H-400), 7.31 (2H, dd, J ¼ 7.3, 7.7 Hz, H-300
and H-500), 7.32 (2H, d, J ¼ 8.6 Hz, H-20 and H-60), 7.41 (2H, d, J ¼ 7.7 Hz,
H-200 and H-600), 7.59 (2H, dd, J ¼ 7.5, 8.1 Hz, H-3000 and H-5000), 7.72 (1H,
tt, J ¼ 7.5, 1.3 Hz, H-4000), 8.17 (2H, d, J ¼ 8.1 Hz, H-2000 and H-
6000); 13C NMR (acetone-d6): ꢀ 29.5 (C-1), 45.5 (C-2), 50.9 (C-4), 69.2 (C-
5), 122.5 (C-30 and C-50), 127.2 (C-200 and C-600), 128.2 (C-400), 129.4 (C-300
and C-500), 129.6 (C-3000 and C-5000), 129.8 (C-7), 130.2 (C-20 and C-60),
130.6 (C-10), 130.7 (C-2000 and C-6000), 133.4 (C-6), 134.6
(C-4000), 138.0 (C-100), 140.2 (C-1000), 150.3 (C-40), 165.6 (COO), 208.6
(C-3); EIMS: m/z 400 (Mþ, 14), 382 (28), 268 (52),
331 (56), 105 (100). HRMS: Calcd. for C26H24O4: 400.1675,
Found: 400.1674.

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Diarylheptanoids
1031
4.3.4. (4E,6E)-1-(4-Benzoyloxyphenyl)-7-Phenylhepta-4,6-
dien-3-one (19)
To a solution of ketol 18 (0.29 g, 0.73 mmol) in benzene (10 mL) was
added a catalytical amount of TsOH and activated molecular sieves 4 A.
The resulting solution was heated under reflux for 10 min, cooled and
diluted with ether. The solution was washed with water, brine, dried, and
evaporated to give compound 19, M.p. (toluene) 92.7–94.7ꢀC. The diene
19 was used in the next step without purification. IR (KBr): (ꢁmax cmꢁ1
)
3068, 3035, 2933, 1737, 1730, 1680, 1664, 1264, 1059; 1H NMR (CDCl3):
ꢀ 2.93 (2H, t, J ¼ 7.3 Hz, H-2), 2.99 (2H, t, J ¼ 7.3 Hz, H-1), 6.28 (1H, d,
J ¼ 15.3 Hz, H-4), 6.86 (1H, dd, J ¼ 10.5, 15.6 Hz, H-6), 6.93 (1H, d,
J ¼ 15.6 Hz, H-7), 7.12 (2H, d, J ¼ 8.3 Hz, H-30 and H-50), 7.26 (2H, d,
J ¼ 8.3 Hz H-20, and H-60), 7.34 (4H, m, H-5, H-300, H-400, and H-500), 7.46
(2H, J ¼ 8.1 Hz, H-200 and H-600), 7.49 (2H, dd, J ¼ 8.1, 7.5 Hz, H-3000 and
H-5000), 7.61 (1H, t, J ¼ 7.5 Hz, H-4000), 8.19 (2H, d, J ¼ 8.1 Hz, H-2000 and
H-6000); 13C NMR (CDCl3): ꢀ 29.6 (C-1), 42.3 (C-2), 121.7 (C-30 and C-50),
126.7 (C-6), 127.3 (C-200 and C-600), 128.6 (C-20 and C-60), 128.8 (C-3000
and C-5000), 129.2 (C-400), 129.3 (C-10), 129.4 (C-300 and C-500), 130.2 (C-2000
and C-6000), 133.5 (C-4000), 136.0 (C-100), 138.9 (C-1000), 141.5 (C-7), 142.8
(C-5), 149.3 (C-40), 165.3 (COO), 199.1 (C-3); EIMS: m/z 382 (Mþ, 70),
291 (6), 287 (10), 105 (100); HRMS: Calcd. for C26H22O3: 382.1569,
Found: 382.1568.
4.3.5. (4E,6E)-1-(4-Hydroxyphenyl)-7-Phenylhepta-4,6-dien-
3-one (14) From 17
To a solution of TMS-ether 17 (0.163 g, 0.35 mmol) in MeOH (5 mL)
was added anhydrous K2CO3 (0.097 g, 0.7 mmol) and the solution was
stirred at room temperature for 3 h. The reaction was quenched with
0.1 N HCl by adjusting to pH 8. The methanol was evaporated, and
the residue extracted with EtOAc, washed with brine, dried, and evapo-
rated. The obtained oil was separated on a silica gel column with CH2Cl2
as eluent to yield ketone 14 (0.048 g, 49%). For analytical data, see 4.3.6.
4.3.6. (4E,6E)-1-(4-Hydroxyphenyl)-7-Phenylhepta-4,6-dien-
3-one (14) From 19
To a solution of diene 19 (0.24 g, 0.63 mmol) in MeOH (12 mL) was
added anhydrous K2CO3 (0.02 g, 0.15 mmol). The solution was stirred at

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1032
Baranovsky et al.
room temperature for 0.5 h and reaction was quenched with 0.1 N HCl by
adjusting to pH 8. Water was added, and the mixture was extracted with
EtOAc. The organic phase was washed with brine, dried, and evaporated.
The obtained oil was purified as above to yield ketone 14 (0.11 g, 65%),
M.p. (hexane-ether) 129.3–130.0ꢀC. IR (neat): (ꢁmax cmꢁ1) 3359, 3027,
1
1664, 1645, 1614, 1223; H NMR (CDCl3): ꢀ 2.82 (2H, t, J ¼ 7.6, H-2),
2.83 (2H, t, J ¼ 7.6, H-1), 6.19 (1H, d, J ¼ 15.4 Hz, H-4), 6.67 (2H, d,
J ¼ 8.3 Hz, H-30 and H-50), 6.84 (1H, d, J ¼ 15.4 Hz, H-7), 7.00 (2H, d,
J ¼ 8.5 Hz, H-20 and H-60), 6.77 (1H, dd, J ¼ 15.4, 10.5, H-6), 7.23 (1H,
dd, J ¼ 15.4, 10.5 Hz, H-5), 7.26 (1H, m, H-300, H-400 and H-500), 7.37 (2H,
d, J ¼ 8.5 Hz, H-200 and H-600); 13C NMR (CDCl3): ꢀ 30.3 (C-1), 42.9 (C-
2), 115.2 (C-30 and C-50), 126.5 (C-6), 127.0 (C-200 and C-600), 128.5 (C-300
and C-500), 128.9 (C-400), 129.2 (C-20 and C-60), 129.2 (C-4), 133.3 (C-10),
135.6 (C-100), 141.3 (C-7), 142.8 (C-5), 154.0 (C-40), 199.7 (C-3); EIMS:
m/z 278 (Mþ, 100), 184 (30), 171 (50), 157 (90), 128 (70); HRMS: Calcd.
for C19H18O2: 278.1307, Found: 278.1307.
4.3.7. (3E)-4-(3,4-Dihydroxyphenyl)-But-3-en-2-one (21)
3,4-Dihydroxybenzaldehyde 20 (1.38 g, 10 mmol) and acetone (5 mL,
66 mmol) were dissolved in degassed acetonitrile (30 mL). Subsequently,
piperidine (0.247 mL, 2.5 mmol), acetic acid (0.143 mL, 2.5 mmol) and
molecular sieves 4A (0.3 g) were added to the solution, and the resulting
purple mixture was refluxed for 4 h. The solution was cooled and solvent
was evaporated. The residue obtained was dissolved in a small amount of
acetone and absorbed on silica gel, and acetone was evaporated. The
resultant material was purified on
a
silica gel column with
CHCl3:EtOAc 95:5 as eluent to yield the yellow ketone 21 (0.95 g, 53%)
which was identical to the described compound,[31] M.p. 177.3–178.0ꢀC
(lit. 175–177ꢀC, water). H NMR (acetone-d6): ꢀ 2.28 (3H, s, H-1), 6.54
1
(1H, d, J ¼ 16.3 Hz, H-3), 6.88 (1H, d, J ¼ 8.1 Hz, H-50), 7.06 (1H, dd,
J ¼ 1.7, 8.1 Hz, H-60), 7.17 (1H, d, J ¼ 1.7 Hz, H-20), 7.48 (1H, d,
J ¼ 16.3 Hz, H-4); 13C NMR (acetone-d6): ꢀ 27.3 (C-1), 115.2 (C-50),
116.4 (C-20), 122.7 (C-60), 125.3 (C-3), 127.9 (C-10), 144.2 (C-4), 146.4
(C-30), 148.8 (C-40), 197.8 (C-2); EIMS: m/z 178 (Mþ, 84), 163 (100).
4.3.8. 4-(3,4-Dihydroxyphenyl)-Butan-2-one (22)
To a solution of ketone 21 (1.16 g, 6.5 mmol) and ammonium for-
mate (0.82 g, 13 mmol) in methanol (20 mL) was carefully added 10%

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Diarylheptanoids
1033
palladium on charcoal (0.67 g) and the resulted mixture was stirred
for 10 min at room temperature. To this was added acetone
(2.5 mL, 33 mmol) and the solution was stirred for another 50 min
after which the catalyst was filtered off and washed with CHCl3,
and the combined filtrates were evaporated. The obtained oil was pur-
ified on a silica gel column with CHCl3:EtOAc 80:20 as eluent to
yield the colorless ketone 22 (1.06 g, 90%), in all respects
identical to the described compound[32] M.p. 85.5–85.8ꢀC (lit.
85–86ꢀC, ether). H NMR (acetone-d6): ꢀ 2.08 (3H, s, H-1), 2.69 (4H,
1
m, H-3 and H-4), 6.52 (1H, dd, J ¼ 1.9, 8.1 Hz, H-60), 6.69 (1H, d,
J ¼ 1.9 Hz, H-20), 6.72 (1H, d, J ¼ 8.1 Hz, H-50); 13C NMR (acetone-d6):
ꢀ 29.8 (C-1), 29.7 (C-4), 46.6 (C-3), 116.0 and 116.2 (C-20 and C-50),
120.2 (C-60), 133.9 (C-10), 143.9 (C-40), 145.7 (C-30), 207.8 (C-2); EIMS:
m/z 180 (Mþ, 80), 137 (50), 123 (100); HRMS: Calcd. for
C10H12O3: 180.0786, Found: 180.0787.
4.3.9. 4-[3,4-bis-(1-Ethoxyethoxy)-Phenyl]-Butan-2-one (23)
Pyridinium p-toluenesulfonate (0.18 g, 10 mol%) was added to a
solution of ketone 22 (1.29 g, 7.15 mmol) in ethyl ether (25 mL) and
vinyl ethyl ether (15 mL). The resulting solution was stirred for 24 h
at room temperature. When the reaction was complete, the
solution was diluted with hexane, separated from the catalyst by decant-
ing, washed with water, brine, dried over Na2SO4, and evaporated to
give ketone 23 as oil (2.20 g). The product was sufficiently pure
for using in the next step. A small amount was purified for an analytical
purposes on a silica gel column with CH2Cl2 as eluent to give a slightly
yellow oil in 95% yield. IR (neat): (ꢁmax cmꢁ1) 2982, 2936, 1715,
1
1600, 1263, 1107, 947; H NMR (acetone-d6): ꢀ 1.13 (6H, m, CH3CH2),
1.41 (6H, m, CH3CH), 2.08 (3H, s, H-1), 2.75 (4H, m, H-3 and
H-4), 3.55 (2H, m, CH3CH2), 3.79 (2H, m, CH3CH2), 5.32 (1H, q,
J ¼ 5.3 Hz, CH3CH), 5.37 (1H, dq, J ¼ 5.3, 2.1 Hz, CH3CH), 6.79 (1H,
dd, J ¼ 2.1, 8.2 Hz, H-60), 6.96 (1H, d, J ¼ 2.1 Hz, H-20), 6.97 (1H, d,
J ¼ 8.2 Hz, H-50); 13C NMR (acetone-d6): ꢀ 15.55/15.56 (CH3CH2),
20.86/20.89/20.90/20.93 (CH3-CH), 29.76 (C-4), 29.83 (C-1), 45.33
(C-3),
62.34/62.38/62.42/62.47
(CH3CH2), 101.56/101.64/101.68/
101.75 (CH3-CH), 120.42/120.46 and 120.52/120.58 (C-20 and C-50),
123.06/123.10 (C-60), 136.93/136.98 (C-10), 146.92/146.99 (C-40),
148.78/148.85 (C-30), 207.24 (C-2); EIMS: m/z 324 (Mþ, 10), 252 (65),
180 (90), 123 (70); HRMS: Calcd. for C18H28O5: 324.1937, Found:
324.1935.

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1034
Baranovsky et al.
4.3.10. (4E,6E)-1-[3,4-bis-(1-Ethoxyethoxy)-Phenyl]-7-
Phenylhepta-4,6-dien-3-one (24)
To a stirred solution of LDA (1.12 mmol) in THF (5 mL) at ꢁ78ꢀC
was added a solution of ketone 23 (0.246 g, 0.76 mmol) in THF (5 mL).
After 15 min, cinnamic aldehyde (0.092 mL, 0.7 mmol) in THF (5 mL)
was added. The almost colorless mixture was stirred for 30 min at the
indicated temperature and TMSCl (0.12 mL, 0.95 mmol) was added in
one portion. The cooling bath was removed and solution was allowed
to warm to ambient temperature. After 30 min DBU (0.12 mL, 0.8 mmol)
was added and the mixture was refluxed for 3 h. The mixture was cooled
and the reaction quenched with saturated NH4Cl and diluted with
EtOAc. The organic phase was washed with water and brine, dried and
evaporated. The obtained oil was purified on a silica gel column with
EtOAc:hexane 1:9 as eluent to give ketone 24 as yellow oil (0.147 g, 44%).
IR (neat): (ꢁmax cmꢁ1) 2977, 2932, 1683, 1660, 1619, 1265, 942; 1H NMR
(CDCl3): ꢀ 1.20 (6H, m, CH3CH2), 1.48 (6H, m, CH3CH), 2.89 (4H, m,
H-1 and H-2), 3.57 (2H, m, CH3CH2), 3.84 (2H, m, CH3CH2), 5.30 (1H,
q, J ¼ 5.1 Hz, CH3CH), 5.34 (1H, q, J ¼ 5.1 Hz, CH3CH), 6.27 (1H, d,
J ¼ 15.5 Hz, H-4), 6.80 (1H, dd, J ¼ 1.3, 8.2 Hz, H-60), 6.85 (1H, dd,
J ¼ 15.5, 10.5 Hz, H-6), 6.92 (1H, d, J ¼ 15.5 Hz, H-7), 6.94 (1H, d,
J ¼ 1.3 Hz, H-20), 6.99 (1H, d, J ¼ 8.2 Hz, H-50), 7.31 (2H, m, H-400 and
H-5), 7.35 (2H, dd, J ¼ 7.8, 7.2 Hz, H-300 and H-500), 7.45 (2H, d,
J ¼ 7.8 Hz, H-200 and H-600); 13C NMR (CDCl3): ꢀ 15.23, 15.27
(CH3CH2), 20.45/20.49/20.50/20.56 (CH3-CH), 29.72 (C-1), 42.32 (C-2),
61.96/62.01/62.19/62.24 (CH3CH2), 101.06/101.13/101.13/101.20 (CH3-
CH), 119.84/119.90 and 119.98/120.05 (C-20 and C-50), 122.56/122.63
(C-60), 126.66 (C-6), 127.24 (C-200 and C-600), 128.45 (C-300 and C-500),
129.21 (C-400), 129.56 (C-4), 135.99/136.03 (C-10), 136.11 (C-100), 141.41
(C-7), 142.69 (C-5), 146.03/146.06 (C-40), 147.78/147.82 (C-30), 199.32 (C-
3); EIMS: m/z 438 (Mþ, 10), 366 (25), 321 (20), 294 (100), 157 (50);
HRMS: Calcd. for C27H34O5: 438.2406, Found: 438.2405.
4.3.11. (4E,6E)-1-(3,4-Dihydroxyphenyl)-7-Phenylhepta-4,6-
dien-3-one (12) From 23
To a stirred solution of LDA (1.78 mmol) in THF (5 mL) at ꢁ78ꢀC
was added a solution of ketone 23 (0.45 g, 1.36 mmol) in THF (5 mL) via
a syringe. The reaction mixture was stirred for 15 min and a solution of
cinnamic aldehyde (0.182 mL, 1.38 mmol) in THF (5 mL) was added. The
mixture was stirred for 30 min at the indicated temperature, after which

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Diarylheptanoids
1035
the cooling bath was removed and the solution allowed to warm to
ambient temperature and stirred for an additional 1 h. The reaction mix-
ture was cooled again to ꢁ30ꢀC, quenched with saturated NH4Cl and
extracted with EtOAc. The organic phase was washed with brine, dried,
and evaporated. The obtained oil was dissolved in methanol (5 mL) and a
few crystals of TsOH were added. After 5 min the solvent was evaporated
without heating and the resulting dark orange oil was dissolved in a 1:1
mixture of benzene:THF (8 mL). TsOH (0.026 g, 0.14 mmol) was added
and the mixture was stirred for 48 h at room temperature. The solvent
was evaporated and the residue was separated on a silica gel column with
EtOAc:hexane 3:7 as eluent to give ketone 12 as yellow oil (0.15 g, 38%).
For analytical data, see 4.3.12.
4.3.12. (4E,6E)-1-(3,4-Dihydroxyphenyl)-7-Phenylhepta-4,6-
dien-3-one (12) From 24
To a solution of ketone 24 (0.308 g, 0.7 mmol) in methanol (5 mL),
TsOH (0.010 g, 0.05 mmol) was added. After 5 min the solvent was evap-
orated without heating and the resulting dark orange oil was purified on
a silica gel column with EtOAc:hexane 3:7 as eluent to give ketone 12
(0.197 g, 96%). IR (neat): (ꢁmax cmꢁ1) 3357, 3028, 1642, 1610, 1281, 997;
1H NMR (CDCl3): ꢀ 2.88 (2H, t, J ¼ 7.2 Hz, H-1), 2.90 (2H, t, J ¼ 7.2 Hz,
H-2), 6.28 (1H, d, J ¼ 15.3 Hz, H-4), 6.65 (1H, dd, J ¼ 2.0, 8.2 Hz, H-60),
6.76 (1H, d, J ¼ 2.0 Hz, H-20), 6.79 (1H, d, J ¼ 8.2 Hz, H-50), 6.87 (1H, dd,
J ¼ 10.3, 15.3 Hz, H-6), 6.95 (1H, d, J ¼ 15.3 Hz, H-7), 7.35 (4H, m, H-5,
H-300, H-400 and H-500), 7.47 (2H, d, J ¼ 7.2 Hz, H-200 and H-600);
13C NMR (CDCl3): ꢀ 29.7 (C-1), 42.5 (C-2), 115.2 and 115.4 d (C-20
and C-50), 120.4 (C-60), 127.7 (C-6), 127.3 (C-200 and C-600), 128.9 (C-300
and C-500), 129.2 (C-400), 129.5 (C-4), 133.9 (C-10), 136.0 (C-100), 141.5 (C-
7), 142.2 (C-40), 142.9 (C-5), 143.9 (C-30), 199.9 (C-3); EIMS: m/z 294
(Mþ, 100), 223 (15), 184 (30), 171 (50), 157 (100), 128 (70); HRMS:
Calcd. for C19H18O3: 294.1256, Found: 294.1255.
4.3.13. 3,4-Di-(1-Ethoxyethoxy)-Benzaldehyde (25)
Pyridinium p-toluenesulfonate (0.75 g, 10 mol%) was added to the
solution of aldehyde 20 (4.14 g, 30 mmol) in diethyl ether (30 mL) and
vinyl ethyl ether (37 mL). The resulting solution was stirred for 3 d at
room temperature. When protection was complete, the solution was
diluted with hexane, separated from the catalyst by decanting, washed

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1036
Baranovsky et al.
with water, brine, dried over Na2SO4, and evaporated (8.46 g). The prod-
uct was further purified on a silica gel column with EtOAc:hexane 1:9 as
eluent to give aldehyde 25 (7.67 g, 91%). IR (neat): (ꢁmax cmꢁ1) 2978,
2934, 2897, 1695, 1596, 1582, 1512, 1435, 1382, 1344, 1271, 1230;
1H NMR (acetone-d6): ꢀ 1.17 (6H, m, CH3CH2), 1.50 (6H, m,
CH3CH), 3.58 (2H, m, CH3CH2), 3.80 (2H, m, CH3CH2), 5.45 (1H,
dq, J ¼ 1.9, 5.4 Hz, CH3CH), 5.59 (1H, q, J ¼ 5.4 Hz, CH3CH), 7.27
(1H, d, J ¼ 8.5 Hz, H-5), 7.56 (1H, m, H-6), 7.60 (1H, d, J ¼ 2.0 Hz, H-
2), 9.82 (1H, s, CHO); 13C NMR (acetone-d6): ꢀ 15.50/15.52 (CH3CH2),
20.54/20.55/20.66/20.70 (CH3CH), 63.08/63.10/63.26/63.28 (CH3CH2),
101.84/101.87/102.44/102.45 (CH3CH), 118.39/118.47 (C-5), 119.60/
119.81 (C-2), 127.73/127.77 (C-6), 132.43/132.46 (C-1), 148.85/148.90
(C-3), 154.99/155.00 (C-4), 192.73 (CHO). HRMS: Calcd. for
C15H22O5: 282.1467, Found: 282.1473.
4.3.14. [3,4-bis-(1-Ethoxyethoxy)-Phenyl]-Methanol (26)
Sodium borohydride (0.20 g, 5.26 mmol) was added portionwise to a
solution of aldehyde 25 (5.03 g, 17 mmol) in a mixture of CH2Cl2–MeOH
(50 mL, 1:1) at ꢁ5ꢀC over 5 min. The resulting solution was stirred for
0.5 h and then the reaction was quenched with solid NH4Cl followed by
addition of water. The organic phase was separated, washed with brine,
dried, and evaporated to give alcohol 26 as pale yellow oil (5.10 g). The
product was used without purification. IR (neat): (ꢁmax cmꢁ1) 3453, 2982,
2936, 2891, 1500, 1267, 1034; 1H NMR (acetone-d6): ꢀ 1.14 (6H, m,
CH3CH2), 1.43 (6H, m, CH3CH), 3.56 (2H, m, CH3CH2), 3.80 (2H, m,
CH3CH2), 4.54 (2H, brs, CH2OH), 5.36 (1H, q, J ¼ 5.2 Hz, CH3CH), 5.39
(1H, q, J ¼ 5.2 Hz, CH3CH), 6.93 (1H, m, H-6), 7.03 (1H, d, J ¼ 8.1 Hz,
H-5), 7.11 (1H, d, J ¼ 2.1 Hz, H-2); 13C NMR (acetone-d6): ꢀ 15.58
(CH3CH2), 20.90/20.93/20.93/20.97 (CH3CH), 62.47/62.49/62.49/62.54
(CH3CH2), 64.33 (CH2OH), 101.67/101.75/101.78/101.85 (CH3CH),
118.79/118.97 (C-2), 120.28/120.40 (C-5), 121.57/121.61 (C-6), 138.16/
138.21 (C-1), 147.71/147.78 (C-4), 148.86/148.93 (C-3). HRMS: Calcd.
for C15H24O5: 284.1624, Found: 284.1622.
4.3.15. Acetic acid 3,4-bis-(1-Ethoxyethoxy)-Benzyl ester (27)
To a solution of alcohol 26 (5.10 g, 17 mmol) and pyridine (1.91 mL,
23.8 mmol) in CH2Cl2 (30 mL) at room temperature was added acetic
anhydride (1.93 mL, 20.4 mmol). The resulted solution was stirred for

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Diarylheptanoids
1037
1 h and then saturated NaHCO3 was added. The organic phase was
separated, washed with brine, dried, and evaporated to give acetate 27
as a pale yellow oil (5.90 g). The product was used without purification.
IR (neat): (ꢁmax cmꢁ1) 2982, 2945, 2891, 1738, 1509, 1038; 1H NMR
(acetone-d6): ꢀ 1.14 (6H, m, CH3CH2), 1.44 (6H, m, CH3CH), 2.03
(3H, s, OAc), 3.57 (2H, m, CH3CH2), 3.80 (2H, m, CH3CH2), 5.00
(2H, s, CH2OAc), 5.39 (2H, m, CH3CH), 6.98 (1H, m, H-6), 7.08 (1H,
d, J ¼ 8.4 Hz, H-5), 7.14 (1H, d, J ¼ 1.9 Hz, H-2); 13C NMR (acetone-d6):
ꢀ 15.54 (CH3CH2), 20.80/20.83/20.83/20.86 (CH3CH and CH3CO),
62.37/62.40/62.43/62.46 (CH3CH2), 66.16 (CH2OAc), 101.61/101.68/
101.69/101.76 (CH3CH), 119.99/120.09 (C-20), 120.59/120.70 (C-50),
123.50/123.54 (C-60), 131.83/131.88 (C-10), 148.69/148.75/148.78/148.83
(C-30 and C-40), 170.82 (CO); HRMS: Calcd. for C17H26O6: 326.1732,
Found: 284.1729.
4.3.16. (4E)-3-Hydroxy-5-phenylpent-4-enoic acid 3,4-bis-(1-
Ethoxyethoxy)-Benzyl ester (28)
To a stirred solution of LDA (3.6 mmol) in THF (10 mL) at ꢁ78ꢀC
was added a solution of acetate 27 (1.02 g, 3 mmol) in THF (7 mL) via
a syringe. After 15 min cinnamic aldehyde (0.4 mL, 3 mmol) in THF
(5 mL) was added. The mixture was stirred for 20 min at the indicated
temperature and the reaction was quenched with saturated NH4Cl. The
solution was allowed to warm to ambient temperature and extracted with
EtOAc. The organic phase was washed with brine, dried, and evaporated.
The obtained residue was purified on a silica gel column with
EtOAc:hexane 1:2 as eluent to give 1.15 g (81%) of hydroxy ester 28.
IR (neat): (ꢁmax cmꢁ1) 3471, 2982, 2932, 2895, 1734, 1505, 1267;
1H NMR (C6D6): ꢀ 1.08 (6H, m, CH3CH2), 1.42 (6H, m, CH3CH), 2.43
(1H, dd, J ¼ 15.4, 4.2 Hz, H-2a), 2.56 (1H, ddd, J ¼ 15.4, 8.3, 2.0 Hz, H-
2b), 3.40 (2H, m, CH3CH2), 3.74 (2H, m, CH3CH2), 4.69 (1H, m, H-3),
4.99 (1H, d, J ¼ 12.2 Hz, CH2OCO), 5.05 (1H, dd, J ¼ 12.2, 4.9 Hz,
CH2OCO), 5.25 (1H, q, J ¼ 5.2 Hz, CH3CH), 5.30 (1H, q, J ¼ 5.2 Hz,
CH3CH), 6.12 (1H, dd, J ¼ 16.1, 5.7 Hz, H-4), 6.59 (1H, d, J ¼ 16.1 Hz,
H-5), 6.89 (1H, brd, J ¼ 8.3 Hz, H-600), 7.02 (1H, m, H-500), 7.05 (1H, t,
J ¼ 7.5 Hz, H-40), 7.12 (2H, dd, J ¼ 8.5, 7.5 Hz, H-30 and H-50), 7.21
(2H, d, J ¼ 8.5 Hz, H-20 and H-60), 7.23 (1H, s, H-200); 13C NMR
(C6D6): ꢀ 15.40/15.43 (CH3CH2), 20.54/20.58/20.59/20.62 (CH3CH),
42.13/42.15
(CH3CH2), 66.25/66.28 (CH2OCO), 69.07 (C-3), 101.13/101.22/101.24/
(C-2),
61.78/61.80/61.92/61.92/61.94/61.95/61.96/61.96

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1038
Baranovsky et al.
101.24/101.26/101.33/101.35/101.38 (CH3CH), 119.72/119.75/119.78/
119.80 (C-500), 120.27/120.33/120.43/120.51 (C-200), 123.23/123.25/
123.30/123.32 (C-600), 126.91 (C-20 and C-60), 127.82 (C-40), 128.80 (C-30
and C-50), 130.52/130.54 (C-5), 130.90/130.92/130.93/130.95 (C-100),
131.04/131.07 (C-4), 137.18 (C-10), 148.47/148.51/148.58/148.62 (C-300),
148.61/148.67/148.70/148.77 (C-400), 171.67/171.69 (C-1). HRMS: Calcd.
for C26H34O7: 458.2305, Found: 458.2300.
4.3.17. (2E,4E)-5-Phenylpenta-2,4-dienoic acid 3,4-bis-(1-
Ethoxyethoxy)-Benzyl ester (29)
To a solution of the hydroxy ester 28 (1.02 g, 2.17 mmol) and DBU
(0.79 mL, 5.2 mmol) in benzene (20 mL) was added acetic anhydride
(0.24 mL, 2.6 mmol). The solution was heated under reflux for 2.5 h,
cooled and evaporated. The residue was filtered through a short silica
gel column to give 0.73 g (74%) of compound 29. IR (neat): (ꢁmax cmꢁ1
)
2979, 2933, 2891, 1715, 1626, 1501, 1129; 1H NMR (C6D6): ꢀ 1.09 (6H, m,
CH3CH2), 1.43 (6H, m, CH3CH), 3.40 (2H, m, CH3CH2), 3.76 (2H, m,
CH3CH2), 5.19 (2H, s, CH2OCO), 5.26 (1H, q, J ¼ 5.2 Hz, CH3CH), 5.31
(1H, q, J ¼ 5.2 Hz, CH3CH), 6.01 (1H, d, J ¼ 15.4 Hz, H-2), 6.41 (1H, d,
J ¼ 15.4 Hz, H-5), 6.53 (1H, dd, J ¼ 15.4, 11.0 Hz, H-4), 6.98 (1H, dd,
J ¼ 8.2, 1.8 Hz, H-600), 7.07 (6H, m, H-20- H-60 and H-500), 7.31 (1H, m, H-
200), 7.56 (1H, dd, J ¼ 15.4, 11.0 Hz, H-3); 13C NMR (C6D6): ꢀ 15.40/15.44
(CH3CH2), 20.62/20.65/20.66/20.70 (CH3CH), 61.96/61.98/61.99/62.00
(CH3CH2), 66.12 (CH2OCO), 101.28/101.30/101.39/101.42 (CH3CH),
119.80/119.87 (C-500), 120.46/120.53 (C-200), 121.50 (C-2), 123.39/123.41
(C-600), 126.43 (C-4), 127.52 (C-20 and C-60), 128.88 (C-30 and C-50),
129.07 (C-40), 131.45/131.47 (C-100), 136.42 (C-10), 140.64 (C-5), 145.22
(C-3), 148.57/148.61 and 148.67/148.70 (C-300 and C-400), 166.54 (C-1);
HRMS: Calcd. for C26H32O6: 440.2199, Found: 440.2205.
4.3.18. (2E,4E)-5-Phenylpenta-2,4-dienoic acid
3,4-dihydroxybenzyl ester (30)
To a solution of the dienoate 29 (0.083 g, 0.18 mmol) in methanol
(1 mL) was added TsOH (10 mg, 0.005 mmol). After 5 min pyridine
(0.1 mL) and water were added. The organic phase was extracted with
EtOAc, washed with brine, dried, and evaporated to give compound 30
(0.057 g, quant), M.p. 108.8–110.6ꢀC (aq. MeOH). IR (KBr): (ꢁmax cmꢁ1
)

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Diarylheptanoids
1039
1
3497, 3381, 2956, 2928, 2854, 1681, 1620, 1519, 1288, 1001; H NMR
(acetone-d6): ꢀ 5.06 (2H, s, CH2), 6.09 (1H, d, J ¼ 15.3 Hz, H-2), 6.78
(1H, dd, J ¼ 8.0, 2.0 Hz, H-600), 6.83 (1H, d, J ¼ 8.0 Hz, H-500), 6.93
(1H, d, J ¼ 2.0 Hz, H-200), 7.10 (2H, m, H-4 and H-5), 7.34 (1H, tt,
J ¼ 7.3, 1.5 Hz, H-40), 7.39 (2H, ddd, J ¼ 8.5, 7.3, 1.5 Hz, H-30 and
H-50), 7.47 (1H, ddd, J ¼ 15.3, 9.1, 1.2 Hz, H-3), 7.58 (2H, dd, J ¼ 8.5,
1.5 Hz, H-20 and H-60); 13C NMR (acetone-d6): ꢀ 66.6 (CH2), 116.0 (C-
500), 116.7 (C-200), 121.2 (C-600), 122.1 (C-2), 127.2 (C-4), 128.0 (C-20 and
C-60), 129.0 (C-100), 129.6 (C-30 and C-50), 129.8, (C-40), 137.1 (C-10), 141.3
(C-5), 145.6 (C-3), 145.9 (C-300), 146.1 (C-400), 167.0 (C-1). HRMS: Calcd.
for C18H16O4: 296.1049, Found: 296.1049.
4.4. Wittig-Horner Synthesis
4.4.1. 3-(3,4-Dihydroxyphenyl)-Propionic acid methyl ester (31)
To a solution of hydrocaffeic acid (1) (1.80 g, 10 mmol) in methanol
(30 mL) was added acetyl chloride (0.079 g, 1 mmol) and the resulting
solution was stirred at room temperature. After 12 h no starting material
was detected and the solvent was evaporated and the obtained oil was
dried thoroughly under vacuum. 1H NMR (CDCl3): ꢀ 2.54 (2H, t,
J ¼ 7.7 Hz, H-2), 2.78 (2H, t, J ¼ 7.7 Hz, H-3), 3.62 (3H, s, OMe), 6.56
(1H, dd, J ¼ 2.2, 8.2 Hz, H-60), 6.65 (1H, d, J ¼ 2.2 Hz, H-20), 6.71 (1H, d,
J ¼ 8.2 Hz, H-50); 13C NMR (CDCl3): ꢀ 30.3 (C-3), 35.9 (C-2), 51.8
(OCH3), 115.4 (C-20), 115.4 (C-50), 120.6 (C-60), 133.4 (C-10), 142.0 (C-
40), 143.6 (C-30), 173.9 (COOCH3).
4.4.2. 3-[3,4-bis-(1-Ethoxyethoxy)-Phenyl]-Propionic acid
methyl ester (32)
The dried ester 31 was dissolved in a mixture of diethyl ether (15 mL)
and ethyl vinyl ether (14.4 mL). Pyridinium p-toluenesulfonate (0.251 g,
10 mol%) was added to the solution and the resulting mixture was stirred
for 24 h at room temperature. When protection had been completed, the
solution was diluted with hexane, separated from the catalyst by decant-
ing, washed with water and brine, dried over Na2SO4, and evaporated to
yield an oily product (3.5 g). The product was purified on silica gel
column with CH2Cl2 as eluent, giving a slightly yellow oil in 92%
yield. IR (neat): (ꢁmax cmꢁ1) 2982, 2936, 1738, 1600, 1505, 1263, 947;

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1040
Baranovsky et al.
1H NMR (acetone-d6): ꢀ 1.14 (6H, m, CH3CH2), 1.43 (6H, m, CH3CH),
2.59 (2H, t, J ¼ 7.6 Hz, H-2), 2.84 (2H, t, J ¼ 7.6 Hz, H-3), 3.56 (2H, m,
CH3CH2), 3.61 (3H, s, OCH3), 3.81 (2H, m, CH3CH2), 5.34 (1H, q,
J ¼ 5.3 Hz, CH3CH), 5.39 (1H, dq, J ¼ 5.3, 2.1 Hz, CH3CH), 6.81 (1H,
dd, J ¼ 2.1, 8.2 Hz, H-60), 6.70 (1H, d, J ¼ 2.0 Hz, H-20), 6.70 (1H, d,
J ¼ 8.2 Hz, H-50); 13C NMR (acetone-d6) ꢀ 15.55/15.56 (CH3CH2),
20.86/20.89/20.90/20.93 (CH3-CH), 30.94 (C-3), 36.17 (C-2), 51.56
(OCH3), 62.37/62.40/62.47/62.52 (CH3CH2), 101.61/101.69/101.69/
101.76 (CH3-CH), 120.44/120.46 and 120.53/120.58 (C-20 and C-50),
123.10/123.14 (C-60), 136.28/136.33 (C-10), 147.15/147.23 (C-40),
148.82/148.88 (C-30), 173.35 (C-1); EIMS: m/z 324 (Mþ, 10), 252 (65),
180 (90), 123 (70); EIMS: m/z 340 (Mþ, 10), 268 (30), 196 (95), 123 (45);
HRMS: Calcd. for C18H28O6: 340.1886, Found: 340.1885.
4.4.3. 4-[3,4-bis-(1-Ethoxyethoxy)-Phenyl]-2-
Ketobutylphosphonic acid dimethyl ester (33)
To a stirred solution of dimethyl methylphosphonate (2.03 mL,
19 mmol) in THF (30 mL) at ꢁ78ꢀC was added a 1.6 N solution of
MeLi in ether (11.6 mL, 18.6 mmol) via a syringe. The resulting solution
was stirred for 1 h at the indicated temperature and ester 32 (2.36 g,
6.5 mmol) in THF (15 mL) was added dropwise at ꢁ78ꢀC. After this
addition the cooling bath was removed and the reaction was allowed to
warm slowly to room temperature. The reaction was stirred at room
temperature for 3 h, quenched with saturated NH4Cl, and extracted
with EtOAc. The organic phase was washed with brine, dried, and evap-
orated to give an oily material (2.9 g). The product was separated via a
silica gel column with CHCl3 as eluent to give the starting material
(0.23 g, 11%) followed by phosphonate 33 as pale yellow oil (2.45 g,
87%). IR (neat): (ꢁmax cmꢁ1) 2981, 1718, 1600, 1507, 1260, 1034, 948;
1H NMR (acetone-d6): ꢀ 1.14 (6H, m, CH3CH2), 1.42 (6H, m, CH3CH),
2.79 (2H, t, J ¼ 7.4 Hz, H-4), 2.96 (2H, t, J ¼ 7.4 Hz, H-3), 3.18 (2H, d,
2JH-P ¼ 22.5 Hz, H-1), 3.55 (2H, m, CH3CH2), 3.69 (3H, s, OCH3), 3.71
(3H, s, OCH3), 3.80 (2H, m, CH3CH2), 5.33 (1H, q, J ¼ 5.4 Hz, CH3CH),
5.39 (1H, dq, J ¼ 1.4, 5.4 Hz, CH3CH), 6.81 (1H, dd, J ¼ 1.9, 8.0 Hz, H-
60), 6.98 (1H, d, J ¼ 1.9 Hz, H-20), 6.99 (1H, d, J ¼ 8.0 Hz, H-50);
13C NMR (acetone-d6): ꢀ 15.57/15.59 (CH3CH2), 20.88/20.92/20.96/
1
20.99 (CH3CH), 29.48 (C-4), 41.58 (d, JC-P ¼ 126.5 Hz, C-1), 45.89/
45.90 (C-3), 53.04 (OCH3), 53.09 (OCH3), 62.42/62.45/62.55/62.59
(CH3CH2), 101.66/101.73/101.76/101.83 (CH3CH), 120.46/120.52
and 120.56/120.64 (C-20 and C-50), 123.15/123.19 (C-60), 136.62/136.73

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Diarylheptanoids
1041
(C-10), 147.01/147.08 (C-40), 148.88/148.94 (C-30), 201.64 (d, JC-P ¼ 6.0
Hz, C-2); EIMS: m/z 432 (Mþ, 10), 360 (5), 315 (20), 288 (100), 178 (65);
HRMS: Calcd. for C20H33O8P: 432.1913, Found: 432.1921.
2
4.4.4. (4E,6E)-1-[3,4-bis-(1-Ethoxyethoxy)-Phenyl]-7-
Phenylhepta-4,6-dien-3-one (24), Using NaH as Base
To a stirred suspension of NaH (0.019 g of 60% dispersion in mineral
oil, 0.48 mmol) in THF (5 mL) at 0ꢀC was added a solution of phospho-
nate 33 (0.210 g, 0.49 mmol) in THF (5 mL) via a syringe. When the
evolution of gas had ceased, the red solution was cooled to ꢁ30ꢀC and
a solution of cinnamic aldehyde (0.06 mL, 0.46 mmol) in THF (3 mL) was
added. The cooling bath was removed, and the solution was warmed and
then refluxed for 2 h until the red color had faded to yellow. The reaction
mixture was cooled, quenched with saturated NH4Cl, and extracted with
EtOAc. The organic phase was washed with water and brine, dried, and
evaporated. The obtained oil was purified on a silica gel column with
EtOAc:hexane 1:9 as eluent to give ketone 24 (0.093 g, 43%). For analyt-
ical data, see 4.3.10.
4.4.5. (4E,6E)-1-[3,4-bis-(1-Ethoxyethoxy)-Phenyl]-7-
Phenylhepta-4,6-dien-3-one (24), Using DBU as Base
To a stirred solution of phosphonate 33 (0.271 g, 0.62 mmol) in THF
(6 mL) were added DBU (0.096 g, 0.63 mmol) and cinnamic aldehyde
(0.082 g, 0.62 mmol). The resulting solution was refluxed for 4 h and
cooled. The solution was poured in water and the resulting mixture
was extracted with EtOAc. The organic phase was washed with water
and brine, dried and evaporated. The obtained oil was purified using the
method described above (4.4.4.) to yield ketone 24 (0.193 g, 71%).
For analytical data, see 4.3.10.
4.4.6. (4E,6E)-1-(3,4-Dihydroxyphenyl)-7-Phenylhepta-4,6-
dien-3-one (12)
For procedure and analytical data, see 4.3.12.

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1042
Baranovsky et al.
4.4.7. 3-(4-Fluorophenyl)-2-Propenal (34)
To a solution of acetaldehyde (1.01 g, 8.95 mM) in ethanol (10 mL) at
0ꢀC was added 3 M NaOH (4.88 mL, 12.21 mM) and stirring maintained
for 20 min.[30] p-Fluorobenzaldehyde (0.394 g, 8.14 mM) in ethanol
(5 mL) was added dropwise and the reaction allowed to warm to room
temperature and stirred for 90 min. The mixture was poured into water
and adjusted to pH 7.0 by the addition of 1 M HCl. The mixture was
extracted with EtOAc, the organic extract washed with brine, dried
over Na2SO4 and the solvent evaporated. Purification by preparative
TLC (n-hexane:EtOAc 6:1) gave 34 (0.745 g, 61%) as a yellow oil. IR
(KBr): (ꢁmax cmꢁ1) 3067, 3031, 2181, 1683, 1621, 1497, 1450, 1419,
1305, 1279, 978, 942, 761. 1H NMR (MeOH-d4): ꢀ 6.65 (1H, dd,
0
0
0
0
0
J ¼ 16.3, 7.5 Hz, H-2), 7.13 (2H, dd, JH-3 ,H-5 –H-2 ,H-6 ¼ 8.5 Hz, JH-3 ,
¼ 9.0 Hz, H-30, H-50), 7.45 (1H, d, J ¼ 16.3 Hz, H-3), 7.57 (2H,
0
H-50–F-4
0
0
0
0
0
0
0
0
0
dd, JH-2 ,H-6 –H-3 ,H-5 ¼ 8.5 Hz, JH-2 ,H-6 –F-4 ¼ 5.2 Hz, H-2 ,H-6 ), 9.69
(1H, d, J ¼ 7.5 Hz, H-1); 13C NMR (MeOH-d4):
ꢀ
116.4 (d,
2JC-F ¼ 22 Hz, C-30,50), 128.3 and 128.4 (C-2 and C-10), 130.5 (d,
3JC-F ¼ 9 Hz, C-20,60), 151.3 (C-3), 164.5 (d, JC-F ¼ 253 Hz, C-40), 193.4
1
(C-1); EIMS: m/z 150 (Mþ, 100).
4.4.7. (4E,6E)-1-(3,4-Dihydroxyphenyl)-7-(4-Fluorophenyl)-
4,6-Heptadien-3-one (36)
A solution of freshly prepared aldehyde 34 (0.082 g, 0.55 mM), phos-
phonate 33 (0.235 g, 0.57 mM) and DBU (0.093 g, 0.61 mM) in THF
(10 mL) was heated under reflux for 4 h. The reaction mixture was
poured into water and extracted with EtOAc. The organic extract
was washed with brine and dried over Na2SO4. The EE derivative 35
was not isolated and removal of the solvent immediately resulted in
36 as an yellow oil. Purification by preparative TLC (n-hexane:EtOAc
6:1) gave 36 (0.075 g, 44%). IR (KBr): (ꢁmax cmꢁ1) 3434, 2952, 1701,
1
1618, 1541, 1363, 1283, 1158, 1305, 1113, 995. H NMR (MeOH-d4):
2.77 (2H, t, J ¼ 7.4 Hz, H-1), 2.88 (2H, t, J ¼ 7.4 Hz, H-2), 6.31 (1H, d,
J ¼ 15.4 Hz, H-4), 6.52 (1H, dd, J ¼ 8.2, 2.1 Hz, H-60), 6.66 (1H, d,
J ¼ 2.1 Hz, H-20), 6.67 (1H, d, J ¼ 8.2 Hz, H-50), 6.92 (1H, dd, J ¼ 15.6,
00
00
10.6 Hz, H-6), 7.00 (1H, d, J ¼ 15.6 Hz, H-7), 7.08 (2H, dd, JH-3 ,H-5 –
00
00
00
00
00
H-200,H-600
¼ 8.6 Hz, JH-3 ,H-5 –F-4 ¼ 9.0 Hz, H-3 ,H-5 ), 7.36 (1H, dd,
00
00
00
00
J ¼ 15.4, 10.6 Hz, H-5), 7.55 (2H, dd, JH-2 ,H-6 –H-3 ,H-5 ¼ 8.6 Hz,
00
00
JH-2 ,H-6 –F-4 ¼ 5.4 Hz, H-2 ,H-6 ); 13C NMR (MeOH-d4): ꢀ 31.0 (C-1),
00
00
00
43.3 (C-2), 116.4 and 116.5 (C-20 and C-50), 116.7 (d, JC-F ¼ 22 Hz,
2

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Diarylheptanoids
1043
C-300, C-500), 120.6 (C-60), 127.8 and 127.9 (C-6 and C-100), 130.4 (d,
3JC-F ¼ 8 Hz, C-200, C-600), 130.5 (C-4), 134.1 (C-10), 141.6 (C-7), 144.5
(C-40), 144.9 (C-5), 146.2 (C-30), 164.5 (d, JC-F ¼ 247 Hz, C-400), 202.8
1
(C-3); EIMS: m/z 312 (Mþ, 98), 175 (100); HRMS: Calcd. for
C19H17O3F: 312.1162, Found: 312.1156.
ACKNOWLEDGMENTS
The authors thank Dr. Neil J. Oldham and Janine Rattke, Jena, for
mass spectra. This investigation was supported financially by the
Deutsche Forschungsgemeinschaft (Bonn) and the Fonds der
Chemischen Industrie (Frankfurt/Main).
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Received in the UK January 25, 2002

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