Synthesis of magnaldehydes B and e and dictyobiphenyl B by microwave-promoted cross-coupling of boronophenols

Article abstract of DOI:10.1002/ejoc.201500350

Magnaldehydes B and E along with their 4′-methylated derivatives are naturally occurring 2,4′-biphenols that have been isolated from the Magnoliaceae. Herein, these natural products have been synthesized from a common intermediate, which was obtained by a microwave-promoted, heterogeneously catalyzed, and protecting-group-free Suzuki-Miyaura coupling reaction in an aqueous medium. These reaction conditions were also successfully applied to a one-step synthesis of the slime mold metabolite dictyobiphenyl B. A protecting-group-free Suzuki-Miyaura cross-coupling reaction of halophenols and boronophenols by using Pd/C as the catalyst and water as the solvent under microwave irradiation has been used for the synthesis of five biphenol-type natural products.

Full text of DOI:10.1002/ejoc.201500350

FULL PAPER
DOI: 10.1002/ejoc.201500350
Synthesis of Magnaldehydes B and E and Dictyobiphenyl B by Microwave-
Promoted Cross-Coupling of Boronophenols
[a]
[a]
Bernd Schmidt* and Martin Riemer
Keywords: Total synthesis / Natural products / Cross-coupling / Palladium / Biaryls / Phenols
Magnaldehydes B and E along with their 4Ј-methylated de-
rivatives are naturally occurring 2,4Ј-biphenols that have
been isolated from the Magnoliaceae. Herein, these natural
products have been synthesized from a common intermedi-
ate, which was obtained by a microwave-promoted, hetero-
geneously catalyzed, and protecting-group-free Suzuki–
Miyaura coupling reaction in an aqueous medium. These re-
action conditions were also successfully applied to a one-step
synthesis of the slime mold metabolite dictyobiphenyl B.
ties,[7,23,24] cytotoxicity,[25–27] anti-inflammatory activity,
and neuroprotective or neurotrophic activity.
[28]
Introduction
[
29–32]
Al-
The isolation and structural elucidation of secondary me-
tabolites from plants that are used in Chinese folk medicine
continue to attract the interest of the scientific community.
For example, Magnolia officinalis (Magnoliaceae) has been
traditionally used for the treatment of various disorders,
though a wealth of information concerning the bioactivity
and chemistry of magnolol and honokiol is available, con-
siderably less attention has been paid to those secondary
metabolites that are present in the Magnoliaceae but only
in minor quantities. For example, M. officinalis contains
several biphenols with partially oxidized one- or three-car-
bon side chains as well as monomethylated derivatives. The
[
1]
[2,3]
such as gastric distension, inflammation,
and clinical
[
4]
depression. From the bark of this plant, the neolignans
magnolol and honokiol[ have been isolated in quantities
that account for 1.5% of the original mass of material,
which makes them the most abundant low molecular weight
5]
[1]
bioactivities of these compounds, named magnaldehydes,
have been underexplored. We are, for example, aware of
only two in vitro studies of the activity of magnaldehydes B
[
1]
constituents present in Magnolia officinalis (Figure 1).
Interestingly, some of the pharmacological activities re-
ported for preparations that contain Magnoliaceae, which
[33,34]
and E against selected cancer cell lines.
In addition,
one study documents the inhibition of lung tumor growth
[35]
in vivo by using magnaldehyde B (Figure 1).
[4]
[2,3]
include anxiolytic activity, anti-inflammatory activity,
or activity against gastrointestinal disorders,[ can be di-
rectly correlated to the presence of magnolol and/or hono-
kiol, Even more interesting, however, is the discovery that
magnolol and honokiol demonstrate activity against dif-
6]
[
7,8]
ferent tumor cell lines,
for example, colon and liver can-
cer cells, by inducing apoptosis[9,10] and inhibiting angio-
[
9]
[
10]
genesis.
It has also been shown that magnolol can sup-
press metastasis by down-regulating certain matrix metall-
[
11]
oproteinases.
In light of these interesting biological ac-
tivities, it is not surprising that several syntheses of both
[
12–14]
[15–21]
magnolol
and honokiol
have been published. In
addition, with a view towards the elucidation of structure–
activity relationships and the discovery of derivatives with
improved bioactivity, numerous non-natural analogues have
[
22]
been synthesized
and evaluated for antimicrobial activi-
[
a] Universität Potsdam, Institut für Chemie,
Karl-Liebknecht-Strasse 24–25, Haus 25, 14476 Potsdam-
Golm, Germany
E-mail: bernd.schmidt@uni-potsdam.de
http://www.chem.uni-potsdam.de/groups/schmidt/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500350.
Figure 1. Structures of magnolol, honokiol, and magnaldehydes B
and E along with their monomethyl ethers.
3760
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Synthesis of Magnaldehydes B and E and Dictyobiphenyl B
We thought that the small quantities of magnaldehydes Results and Discussion
available from natural sources as well as laborious isolation
and purification procedures would impede further bio-
By starting from commercially available p-hydroxybenz-
logical evaluation. Therefore, the chemical synthesis of the aldehyde (5), we prepared monobrominated product 6 by
magnaldehydes would be useful to provide material for bio- following
activity tests and structure validation. To the best of our (Scheme 1).
our
previously
published
procedure
[
37]
In the next step, the o,pЈ-biphenol moiety
knowledge, only magnaldehyde B has previously been syn- was constructed by a Suzuki–Miyaura coupling reaction.
thesized. Takeya et al. used the addition of a 4-allyloxy- These cross-coupling reactions generally require base,
phenyl Grignard reagent to a spirocyclohexadienone as the which is believed to accelerate the transmetalation step by
key step for biphenol formation. From there, magnal- enhancing the nucleophilicity of the boronic acid through
dehyde B was obtained in four steps.[
36]
the formation of the corresponding boronate (boronate
Previously, we discovered that all of the regioisomeric bi- mechanism) or the substitution of a Pd-bonded halide by
[
39]
phenols can be synthesized by protecting-group-free Su- an alkoxide or hydroxide (oxo-Pd mechanism). We found
zuki–Miyaura coupling reactions of boronophenols and that bases such as NaOH or K CO that are typically used
2
3
halophenols with water as the solvent and commercial Pd/ in Suzuki–Miyaura reactions give very low yields when
C as the precatalyst.[
37,38]
However, the success of the cross- combined with p-boronophenols such as 7, and this might
coupling reactions crucially depends on the appropriate be attributed to the deprotonation of the phenol under
choice of additive and heating conditions to produce the these reaction conditions. However, we also observed signif-
desired positional isomer. On the basis of these experiences, icantly improved yields by combining these boronophenols
[
38]
we investigated the syntheses of magnaldehydes B (3a) and with fluorides as additives. Fluorides are believed to co-
E (4a) along with their 4Ј-methyl ethers 3b and 4b, respec- ordinate to the Pd, increase the nucleophilicity of the sol-
tively, by employing a common intermediate.
vent, that is, water, through hydrogen bonding, and thereby
Scheme 1. Divergent synthesis of magnaldehydes B (3a) and E (4a) along with their 4Ј-monomethyl ethers 3b and 4b, respectively (NBS =
N-bromosuccinimide, p-TSA = para-toluenesulfonic acid, MW = microwave, MOM = methoxymethyl, THF = tetrahydrofuran, DIBAL-H
=
diisobutylaluminum hydride).
Eur. J. Org. Chem. 2015, 3760–3766
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B. Schmidt, M. Riemer
FULL PAPER
facilitate the formation of the crucial Pd-hydroxy intermedi- reduction of resulting enoate 13 to afford allyl alcohol 14,
ates[
40–42]
without extensive deprotonation of the boron- which was then oxidized by treatment with MnO to give
2
ophenol. For these reasons, the Suzuki–Miyaura coupling enal 15. In the next step, the Claisen rearrangement was
of 6 and 7 was performed in the presence of NBu F. Upon performed under the same conditions as those for the prep-
4
microwave irradiation[ in the presence of Pd/C as a cata- aration of magnaldehyde E to furnish MOM-protected
43]
lyst and in an aqueous medium, the desired 4Ј,6-biphenol- magnaldehyde B (16) in 57% yield. Compound 16 was de-
3
-carbaldehyde (8) was obtained within a short reaction protected by using a 10:1 mixture of CH Cl /CF CO H, as
2 2 3 2
time in high yield.
described above for 12, to yield magnaldehyde B (3a) quan-
The 4Ј-hydroxy group was ultimately needed for the in- titatively. The 4Ј-methyl ether 3b was synthesized from 16
stallation of the allyl group at the 3Ј-position through an through O-methylation followed by cleavage of the MOM
O-allylation followed by a Claisen rearrangement. As ether moiety of intermediate 17.
attempts for the selective 4Ј-O-allylation failed, a protecting
Although our syntheses of magnaldehydes B and E and
group detour was required. Although the hydroxy group at their 4Ј-methyl ethers are not entirely protecting-group-free,
the 2-position is sterically more congested, we reasoned that our goal was to minimize the use of protecting group opera-
it should be more acidic as a result of the electron-with- tions. Part of this objective is facilitated by the dual role of
drawing effect of the carbonyl group at the para position. the allyl substituent, which serves as a phenol protecting
By using 1.0 equiv. of MOMBr in the presence of Hünig’s group during the three step conversion of 10 into 15 and
base, we could indeed achieve the regioselective monopro- subsequently as the moiety involved in the Claisen re-
tection and furnish 9 in 89% yield. Subsequent O-allylation arrangement to install the allyl group at the 3Ј-position.
under standard conditions gave 10, which is the key inter- However, more important for protecting group economy
mediate and represents the branching point in our synthesis are the conditions used for the key Suzuki–Miyaura cou-
for the four natural products 3a, 3b, 4a, and 4b. The con- pling reaction of the unprotected halophenol and borono-
firmation of the structure of 10 was accomplished by 2D phenol, that is, microwave irradiation, an aqueous me-
NOE spectroscopy. Strong NOEs between the methylene dium, an immobilized Pd catalyst, and fluorides instead of
protons of the allyl group and the protons at the 3Ј-position hydroxides or carbonates as rate accelerating agents. To
(NOE-1) and between the methylene protons of the MOM underline this point, we investigated the application of these
group and the proton at the 5-position (NOE-2) indicate cross-coupling conditions to the synthesis of dictyobi-
that the protecting group and allyl substituent are indeed phenyl B (20), a metabolite recently isolated from the slime
[
44]
located in the correct positions (Figure 2).
mold Dictyostelium polycephalum by Kikuchi et al. These
authors also synthesized dictyobiphenyl B and three other
newly discovered bi- and terphenyls, because the amount
of material from the biological source was insufficient for
structural confirmation and biological evaluation. To this
end, Kikuchi et al. used a Suzuki–Miyaura coupling reac-
tion of fully protected pinacoloboronate 18 and MOM-pro-
tected 4-bromophenol (19) followed by global deprotection
[
44]
with BBr3.
We suggest an alternative synthesis of
dictyobiphenyl B, in which the roles of the nucleophilic and
Figure 2. Structure validation of 10 through 2D NOE spectroscopy.
From allyl ether 10, we continued towards the synthesis
of magnaldehyde E (4a) and its 4Ј-methyl ether 4b by con-
ducting a microwave-promoted Claisen rearrangement to
install the 3Ј-allyl chain and obtain MOM-protected mag-
naldehyde E (11) quantitatively. Cleavage of the MOM
ether required some optimization. Although treatment with
methanol/HCl resulted in decomposition, no conversion
was observed when 11 was exposed to a 100:1 mixture of
dichloromethane and CF CO H. Quantitative deprotection
3
2
to give magnaldehyde E (4a) was eventually achieved by in-
creasing the amount of CF CO H in the mixture to 10 vol-
3
2
%. From 11, 4Ј-methoxymagnaldehyde E (4b) was synthe-
sized by O-methylation and cleavage of the MOM ether by
using the conditions previously applied to 11.
For the synthesis of magnaldehyde B (3a) and its methyl
ether 3b, elongation of the side chain at the 3-position was
required. This was achieved by submitting aldehyde 10 to
Scheme 2. Kikuchi’s and our synthesis of dictyobiphenyl B [20,
a Horner–Wadsworth–Emmons olefination followed by the dppf = 1,1Ј-bis(diphenylphosphino)ferrocene].
3
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Synthesis of Magnaldehydes B and E and Dictyobiphenyl B
3
electrophilic coupling partners are reversed. By using our (O)CD (δ = 39.5 ppm) as an internal standard. IR spectra were
recorded as attenuated total reflectance (ATR)-FTIR spectra.
conditions for the protecting-group-free Suzuki–Miyaura
coupling of an o-halo-substituted phenol and a p-borono-
phenol, methyl ester 21 underwent a coupling reaction
–
1
Wavenumbers ( ν˜ ) are given in cm . The band intensities are de-
fined as strong (s), medium (m), or weak (w). Low and high resolu-
tion mass spectra were obtained by EI/TOF. Microwave reactions
were carried out in an Anton-Paar monowave 300 reactor at the
reported temperature of the individual procedure (monowave,
maximum power 850 W, temperature control by IR sensor, vial vol-
ume: 20 mL). para-Boronophenol 7 was purchased and used with-
with 7 in the presence of NBu F as an additive. Saponifica-
4
tion of the methyl ester was accomplished in a one-pot fash-
ion by adding KOH to the reaction mixture to give dictyo-
biphenyl B (20). We then checked whether the rate accelera-
tion of the Suzuki–Miyaura coupling reaction followed by out further purification. 3-Bromo-4-hydroxybenzaldehyde (6) was
a saponification could be accomplished by using only one synthesized according to a literature procedure.[ The Pd/C that
additive, namely KOH. To no avail, ester 21 was quantita- was used for all experiments was purchased from Sigma–Aldrich
37]
(
product number 205699, 9.8–10.2% Pd on dry support, reduced,
tively hydrolyzed under these conditions, but 20 could not
be detected. This observation is, however, in line with our
previously reported results regarding hydroxides or hydrox-
average particle size of the carbon is 15 μm, surface area of the
carbon support is 750–1000 m g ).
2
–1 [45]
ide-generating additives being unsuitable promoters of 4Ј,6-Dihydroxy-[1,1Ј-biphenyl]-3-carbaldehyde (8): Compound
Suzuki–Miyaura coupling reactions that involve para- (201 mg, 1.00 mmol), compound (179 mg, 1.30 mmol,
fluoride trihydrate
O, 1.26 g, 4.0 mmol, 4.0 equiv.), and Pd/C (10 wt.-%,
0 mg, 2 mol-%) were suspended in water (12.0 mL) in a vessel
6
7
boronophenols (Scheme 2).
1.30 equiv.),
TBAF·3H
tetra-n-butylammonium
(
2
2
suited for microwave irradiation. The closed vessel was placed in a
microwave reactor and irradiated at 150 °C for 0.5 h. After cooling
the mixture to ambient temperature, it was carefully acidified by
the addition of hydrochloric acid (1.0 m). The resulting mixture was
extracted with methyl tert-butyl ether (MTBE, 3ϫ 50 mL). The
Conclusions
In summary, we have described protecting-group-econ-
omic syntheses of four naturally occurring biphenols that
are present in M. officinalis. By starting from the same com-
mercially available starting materials, we prepared magnal-
dehyde B (19% over nine steps), 4Ј-methoxymagnal-
dehyde B (15% over ten steps), magnaldehyde E (43% over
six steps), and 4Ј-methoxymagnaldehyde E (39% over seven
4
combined organic layers were dried with MgSO , filtered, and con-
centrated under reduced pressure. The residue was purified by col-
umn chromatography on silica to furnish 8 (173 mg, 0.81 mmol,
1
8
1%). H NMR (300 MHz, [D
6
]DMSO): δ = 9.74 (s, 1 H), 8.90 (s,
1
H), 8.59 (s, 1 H), 6.83 (d, J = 2.0 Hz, 1 H), 6.75 (dd, J = 8.3,
steps). The structurally related natural product dictiobi- 2.1 Hz, 1 H), 6.48 (d, J = 8.6 Hz, 2 H), 6.15 (d, J = 8.3 Hz, 1 H),
1
3
phenyl B, originally isolated from the slime mold D. polyce- 5.89 (d, J = 8.6 Hz, 2 H) ppm. C NMR (75 MHz, [D
6
]DMSO):
phalum, was obtained in a single step in 87% yield by start- δ = 191.3, 160.2, 156.7, 132.5, 130.2, 129.6, 128.8, 128.5, 127.8,
1
16.4, 115.0 ppm. IR (ATR): ν˜ = 1663 (w), 1587 (s), 1175 (s), 1123
ing from commercially available starting materials. The ana-
lytical data of the synthesized compounds are in agreement
with those reported in the literature for the natural prod-
–
1
+
+
(
m), 821 (s) cm . HRMS (EI): calcd. for C13
14.0630; found 214.0621.
H
10
O
3
[M]
2
ucts. The key step of our synthesis is the protecting-group- 4Ј-Hydroxy-6-(methoxymethoxy)-[1,1Ј-biphenyl]-3-carbaldehyde (9):
free Suzuki–Miyaura coupling reaction of the appropriately Biphenol 8 (190 mg, 0.89 mmol), NEt(iPr) (0.31 mL, 1.78 mmol,
substituted halophenol with para-boronophenol. This reac- 2.0 equiv.), and 4-(dimethylamino)pyridine (DMAP, 11 mg,
2
0
2 2
.09 mmol, 10 mol-%) were dissolved in CH Cl /THF (2:1, 15 mL),
tion proceeds in aqueous medium, is heterogeneously cata-
lyzed by commercially available Pd/C, and is efficiently pro-
moted by microwave irradiation. The use of fluorides as
additives rather than hydroxides is crucial to the success of
the process.
and the resulting solution was cooled to 0 °C. A solution of
MOMBr (90% technical grade, 80.5 μL, 0.89 mmol, 1.0 equiv.) in
CH Cl (5 mL) was slowly added to the mixture. Upon complete
2 2
addition, the mixture was warmed to ambient temperature and
stirred continuously for 12 h. The solution was acidified by the ad-
dition of hydrochloric acid (1.0 m), and the resulting mixture was
extracted with MTBE (3ϫ 50 mL). The combined organic layers
Experimental Section
were dried with MgSO , filtered, and concentrated under reduced
4
pressure. The residue was purified by column chromatography on
General Methods: All experiments were conducted in dry reaction
vessels under nitrogen. The solvents were purified by standard pro-
cedures. Deionized water was used for the cross-coupling reactions.
1
silica to furnish 9 (204 mg, 0.79 mmol, 89%). H NMR (300 MHz,
CDCl
.5, 2.2 Hz, 1 H), 7.42 (d, J = 8.7 Hz, 2 H), 7.32 (d, J = 8.5 Hz, 1
H), 6.91 (d, J = 8.7 Hz, 2 H), 5.78 (s, 1 H), 5.41 (s, 1 H), 5.25 (s,
3
): δ = 9.94 (s, 1 H), 7.85 (d, J = 2.1 Hz, 1 H), 7.81 (dd, J =
8
1
The H NMR spectroscopic data were recorded at 300 or 500 MHz
in CDCl
dard, in [D
an internal standard, in [D
3
with residual CHCl
]methanol with residual CD
]acetone with residual CD
δ = 2.05 ppm) as an internal standard, or in [D ]DMSO with resid-
]DMSO (δ = 2.50 ppm) as an internal standard. Coupling
3
(δ = 7.26 ppm) as an internal stan-
HOD (δ = 3.31 ppm) as
HC(O)CD
13
2
1
9
3
H), 3.45 (s, 3 H) ppm. C NMR (75 MHz, CDCl ): δ = 191.3,
4
2
59.3, 155.5, 132.5, 132.0, 130.9, 130.9, 130.9, 129.7, 115.3, 115.0,
4.7, 56.6 ppm. IR (ATR): ν˜ = 3347 (br. w), 1683 (s), 1595 (s), 1261
s), 976 (s) cm . HRMS (EI): calcd. for C15
6
2
3
(
6
–1
+
+
(
14 4
H O [M] 258.0887;
ual [D
5
found 258.0871.
13
constants (J) are reported in Hz. The C NMR spectroscopic data
were recorded at 75 MHz in CDCl with CDCl (δ = 77.0 ppm) as
an internal standard, in [D ]methanol with CD OD (δ = 49.2 ppm)
as an internal standard, in [D ]acetone with CD C(O)CD (δ =
9.9 ppm) as an internal standard, or in [D ]DMSO with CD S- were suspended in acetone (20 mL). The mixture was stirred at
3
3
4Ј-(Allyloxy)-6-(methoxymethoxy)-[1,1Ј-biphenyl]-3-carbaldehyde
(10): Compound 9 (274 mg, 1.06 mmol), allyl bromide (183 μL,
2.12 mmol, 2.0 equiv.), and K CO (292 mg, 2.12 mmol, 2.0 equiv.)
2 3
4
3
6
3
3
2
6
3
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B. Schmidt, M. Riemer
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5
0 °C until the starting material was completely consumed. Water pressure to give compound 12 (30 mg, 0.10 mmol, quantitative
was added, and the aqueous phase was extracted with MTBE (3ϫ yield), which was sufficiently pure and used in the next step without
0 mL). The combined organic layers were dried with MgSO , fil-
1
5
4
3
further purification. H NMR (300 MHz, CDCl ): δ = 9.94 (s, 1
tered, and concentrated under reduced pressure. The residue was
H), 7.85 (d, J = 2.1 Hz, 1 H), 7.80 (dd, J = 8.5, 2.1 Hz, 1 H), 7.44–
7.33 (m, 2 H), 7.31 (d, J = 8.5 Hz, 1 H), 6.93 (d, J = 8.4 Hz, 1 H),
purified by column chromatography on silica to furnish 10 (249 mg,
1
0
7
.84 mmol, 79%). H NMR (300 MHz, CDCl
3
): δ = 9.94 (s, 1 H), 6.03 (ddt, J = 16.8, 10.0, 6.6 Hz, 1 H), 5.24 (s, 2 H), 5.16–5.00 (m,
2 H), 3.88 (s, 3 H), 3.46 (s, 3 H), 3.43 (d, J = 7.9 Hz, 2 H) ppm.
.85 (d, J = 2.1 Hz, 1 H), 7.80 (dd, J = 8.5, 2.2 Hz, 1 H), 7.47 (d,
1
3
J = 8.9 Hz, 2 H), 7.32 (d, J = 8.5 Hz, 1 H), 6.99 (d, J = 8.9 Hz, 2
3
C NMR (75 MHz, CDCl ): δ = 191.1, 159.1, 156.9, 136.8, 132.3,
H), 6.09 (ddt, J = 17.2, 10.5, 5.3 Hz, 1 H), 5.45 (ddd, J = 17.3, 3.1, 132.0, 130.9, 130.8, 130.5, 129.3, 128.3, 128.3, 115.6, 114.7, 110.0,
1
4
.6 Hz, 1 H), 5.31 (ddd, J = 10.5, 2.8, 1.4 Hz, 1 H), 5.24 (s, 2 H), 94.5, 56.5, 55.5, 34.2 ppm. IR (ATR): ν˜ = 2917 (br. m), 1691 (s),
1
3
–1
+
20 4
.59 (dt, J = 5.3, 1.5 Hz, 2 H), 3.45 (s, 3 H) ppm. C NMR 1598 (m), 1492 (s), 983 (m) cm . HRMS (EI): calcd. for C19H O
+
(
75 MHz, CDCl
3
): δ = 191.2, 159.3, 158.3, 133.4, 132.5, 132.0, [M] 312.1362; found 312.1347.
1
31.0, 130.7, 130.7, 129.8, 117.9, 115.0, 114.6, 94.7, 69.0, 56.6 ppm.
4
Ј-Methoxymagnaldehyde E (4b): Compound 12 (26 mg,
IR (ATR): ν˜ = 2925 (br. w), 1693 (s), 1598 (s), 1514 (m), 982
–1
+
+
0.08 mmol) was dissolved in CH Cl /CF CO H (10:1, 2.0 mL), and
the resulting mixture was stirred at ambient temperature for 2 h.
The mixture was then diluted with ethyl acetate (50 mL), and the
2
2
3
2
18 4
(s) cm . HRMS (EI): calcd. for C18H O [M] 298.1200; found
2
98.1193.
3
Ј-Allyl-4Ј-hydroxy-6-(methoxymethoxy)-[1,1Ј-biphenyl]-3-carb- solution was washed with brine (3ϫ 10 mL). The organic layer
aldehyde (11): Compound 10 (66 mg, 0.22 mmol) was dissolved in
N,N-diethylaniline (3 mL) in a vessel suited for microwave irradia-
tion. The closed vessel was placed in a microwave reactor and irra-
diated at 250 °C for 1.0 h. After cooling to ambient temperature,
the mixture was diluted with ethyl acetate (50 mL), and the re-
sulting solution was washed with hydrochloric acid (1.0 m, 3ϫ).
was dried with MgSO
4
, filtered, and concentrated under reduced
pressure to give 4b (20 mg, 0.07 mmol, 91%) as the analytically
1
3
pure product. H NMR (300 MHz, CDCl ): δ = 9.89 (s, 1 H), 7.82–
7.73 (m, 2 H), 7.30 (dd, J = 8.3, 2.3 Hz, 1 H), 7.24 (d, J = 2.2 Hz,
1 H), 7.09 (d, J = 8.9 Hz, 1 H), 6.98 (d, J = 8.3 Hz, 1 H), 6.00
(ddt, J = 16.8, 10.1, 6.7 Hz, 1 H), 5.10 (ddd, J = 17.3, 3.2, 1.6 Hz,
1 H), 5.08 (ddd, J = 10.3, 3.2, 1.6 Hz, 1 H), 3.89 (s, 3 H), 3.44 (d,
4
The organic layer was dried with MgSO , filtered, and concentrated
under reduced pressure to give compound 11 (66 mg, 0.22 mmol,
1
3
3
J = 6.6 Hz, 2 H) ppm. C NMR (75 MHz, CDCl ): δ = 191.13,
quantitative yield), which was analytically pure and used in the next
158.40, 157.74, 136.39, 132.56, 131.24, 130.53, 130.42, 130.19,
1
step without further purification. H NMR (300 MHz, CDCl
3
): δ 128.91, 128.02, 127.37, 116.42, 116.22, 111.30, 55.72, 34.37 ppm.
=
1
9.94 (s, 1 H), 7.84 (d, J = 2.1 Hz, 1 H), 7.79 (dd, J = 8.5, 2.1 Hz,
H), 7.35–7.27 (m, 3 H), 6.89 (d, J = 8.1 Hz, 1 H), 6.06 (ddt, J = (s) cm . HRMS (EI): calcd. for C17
268.1095.
IR (ATR): ν˜ = 3228 (br. m), 1668 (m), 1589 (s), 1498 (m), 1246
–
1
+
+
16 3
H O [M] 268.1099; found
1
2
6.6, 10.1, 6.4 Hz, 1 H), 5.45 (s, 1 H), 5.26, (s, 2 H), 5.26–5.12 (m,
H), 3.46 (d, J = 7.22 Hz, 2 H), 3.45 (s, 3 H) ppm. 13C NMR
): δ = 191.3, 159.3, 154.0, 136.5, 132.4, 132.1,
Ethyl (E)-3-[4Ј-(Allyloxy)-6-(methoxymethoxy)-(1,1Ј-biphenyl)-3-yl-
acrylate (13): To a solution of triethyl phosphonoacetate (230 μL,
.15 mmol, 1.5 equiv.) in dry and degassed THF (10 mL) was
added NaH (60 wt.-% dispersion in mineral oil, 46 mg, 1.15 mmol,
.5 equiv.). The mixture was stirred at 65 °C for 1 h and then cooled
(
75 MHz, CDCl
3
]
1
1
5
1
2
31.6, 130.9, 130.8, 129.8, 129.0, 125.4, 116.7, 115.7, 114.9, 94.7,
6.6, 35.2 ppm. IR (ATR): ν˜ = 3331 (br. w), 1683 (m), 1594 (s),
490 (m), 1191 (s) cm . HRMS (EI): calcd. for C18
98.1205; found 298.1208.
–
1
+
+
H
18
O
4
[M]
1
to 0 °C. A solution of 10 (229 mg, 0.77 mmol) in THF (5 mL) was
then added. The mixture was heated to 65 °C for 5 h, cooled to
ambient temperature, and partitioned between ethyl acetate
(50 mL) and brine (20 mL). The aqueous phase was extracted with
MTBE (3ϫ 50 mL). The combined organic layers were dried with
Magnaldehyde E (4a): Compound 11 (20 mg, 0.07 mmol) was dis-
solved in CH Cl /CF CO H (10:1, 2 mL), and the resulting solu-
tion was stirred at ambient temperature for 2 h. The mixture was
diluted with ethyl acetate (50 mL), and the solution was washed
2
2
3
2
with brine (3ϫ 10 mL). The organic layer was dried with MgSO
filtered, and concentrated under reduced pressure to give magnal-
dehyde E (4a, 17 mg, 0.07 mmol, quantitative yield) in analytically 13 (284 mg, 0.77 mmol, quantitative yield). H NMR (300 MHz,
4
,
MgSO
4
, filtered, and concentrated under reduced pressure. The res-
idue was purified by column chromatography on silica to furnish
1
1
pure form. H NMR (300 MHz, [D
.81 (d, J = 2.1 Hz, 1 H), 7.72 (dd, J = 8.3, 2.1 Hz, 1 H), 7.37 (d,
J = 2.2 Hz, 1 H), 7.33 (dd, J = 8.2, 2.3 Hz, 1 H), 7.14 (d, J =
6 3
]acetone): δ = 9.90 (s, 1 H), CDCl ): δ = 7.67 (d, J = 16.0 Hz, 1 H), 7.51–7.40 (m, 4 H), 7.20
7
(d, J = 8.5 Hz, 1 H), 6.98 (d, J = 8.7 Hz, 2 H), 6.36 (d, J = 16.0 Hz,
1 H), 6.09 (ddt, J = 17.3, 10.5, 5.3 Hz, 1 H), 5.45 (dd, J = 17.3,
8
6
1
.3 Hz, 1 H), 6.93 (d, J = 8.2 Hz, 1 H), 6.05 (ddt, J = 16.8, 10.0, 1.3 Hz, 1 H), 5.31 (dd, J = 10.5, 1.1 Hz, 1 H), 5.16 (s, 2 H), 4.59
.7 Hz, 1 H), 5.10 (ddd, J = 17.1, 3.5, 1.6 Hz, 1 H), 5.00 (ddt, J = (d, J = 5.2 Hz, 2 H), 4.26 (q, J = 7.1 Hz, 2 H), 3.42 (s, 3 H), 1.33
0.0, 2.2, 1.2 Hz, 1 H), 3.44 (d, J = 6.6 Hz, 2 H) ppm. 13C NMR (t, J = 7.1 Hz, 3 H) ppm. C NMR (75 MHz, CDCl
]acetone): δ = 191.3, 160.8, 155.4, 138.1, 133.3, 131.8, 158.4, 156.2, 144.5, 133.7, 132.2, 130.9, 130.9, 130.7, 128.9, 128.7,
30.8, 130.6, 130.2, 129.6, 129.1, 127.1, 117.4, 115.7, 115.6, 118.1, 117.0, 115.9, 114.8, 95.2, 69.3, 60.8, 56.6, 14.7 ppm. IR
13
3
): δ = 167.6,
(75 MHz, [D
6
1
3
8
–
1
5.0 ppm. IR (ATR): ν˜ = 3266 (br. w), 1668 (s), 1586 (s), 1188 (s), (ATR): ν˜ = 2929 (br. m), 1709 (s), 1494 (s), 1243 (s), 833 (m) cm .
–1
+
+
+
+
26 (m) cm . HRMS (EI): calcd. for C16
H
14
O
3
[M] 254.0943; HRMS (EI): calcd. for C22
24 5
H O [M] 368.1624; found 368.1625.
found 254.0948.
(
E)-3-[4Ј-(Allyloxy)-6-(methoxymethoxy)-(1,1Ј-biphenyl)-3-yl]prop-
3
Ј-Allyl-4Ј-methoxy-6-(methoxymethoxy)-[1,1Ј-biphenyl]-3-carb-
2-en-1-ol (14): Compound 13 (350 mg, 0.95 mmol) was dissolved in
aldehyde (12): Compound 11 (29 mg, 0.10 mmol) and K CO
2
3
THF (10 mL), and the resulting solution was cooled to –78 °C.
2 2
(28 mg, 0.20 mmol, 2.0 equiv.) were dissolved in acetone (10 mL). DIBAL-H (1 m solution in CH Cl , 2.47 mL, 2.47 mmol,
Methyl iodide (121 μL, 1.90 mmol, 20 equiv.) was added, and the
mixture was stirred at ambient temperature for 12 h. The reaction
mixture was then diluted with water and the aqueous phase was
extracted with MTBE (3ϫ 50 mL). The combined organic layers
2.6 equiv.) was slowly added. The mixture was hydrolyzed by the
addition of brine (10 mL). The aqueous phase was extracted with
MTBE (3ϫ 50 mL). The combined organic layers were dried with
MgSO
4
, filtered, and concentrated under reduced pressure. The res-
4
were dried with MgSO , filtered, and concentrated under reduced
idue was purified by column chromatography on silica to furnish
3764
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 3760–3766

Synthesis of Magnaldehydes B and E and Dictyobiphenyl B
1
4 (308 mg, 0.94 mmol, quantitative yield). 1H NMR (300 MHz, 194.8, 156.1, 154.7, 154.3, 136.0, 131.3, 131.1, 129.8, 129.1, 128.5,
CDCl ): δ = 7.45 (d, J = 8.8 Hz, 2 H), 7.35 (d, J = 2.2 Hz, 1 H), 128.1, 127.2, 126.9, 126.3, 117.0, 116.8, 116.8, 35.0 ppm. IR (ATR):
.29 (dd, J = 8.5, 2.3 Hz, 1 H), 7.15 (d, J = 8.5 Hz, 1 H), 6.94 (t,
J = 17.9 Hz, 2 H), 6.59 (d, J = 15.9 Hz, 1 H), 6.29 (dt, J = 15.8, HRMS (EI): calcd. for C18
.8 Hz, 1 H), 6.09 (ddt, J = 17.2, 10.5, 5.3 Hz, 1 H), 5.45 (ddd, J
3
–
1
7
ν˜ = 3264 (br. m), 1645 (s), 1590 (s), 1491 (m), 1280 (m) cm .
+
+
16 3
H O [M] 280.1099; found 280.1093.
5
=
2
(
E)-3-[3Ј-Allyl-4Ј-methoxy-6-(methoxymethoxy)-(1,1Ј-biphenyl)-3-yl-
17.3, 3.1, 1.5 Hz, 1 H), 5.31 (dd, J = 10.5, 1.4 Hz, 1 H), 5.11 (s,
H), 4.59 (dt, J = 5.3, 1.4 Hz, 2 H), 4.31 (dd, J = 5.9, 1.1 Hz, 2
]acrylaldehyde (17): Compound 16 (28 mg, 0.09 mmol) and K CO
3
2
13
(25 mg, 0.18 mmol, 2.0 equiv.) were suspended in acetone (10 mL).
Methyl iodide (107 μL, 1.72 mmol, 20 equiv.) was added, and the
mixture was stirred at ambient temperature for 12 h. The mixture
was diluted with water, and the aqueous phase was extracted with
MTBE (3ϫ 50 mL). The combined organic layers were dried with
H), 3.40 (s, 3 H) ppm. C NMR (75 MHz, CDCl
1
1
3
): δ = 158.0,
54.0, 133.5, 131.7, 131.0, 130.8, 130.7, 129.1, 127.3, 126.4, 117.8,
15.9, 114.5, 95.2, 69.0, 64.0, 56.3, 27.1 ppm. IR (ATR): ν˜ = 3386
–1
(br. w), 1492 (s), 1242 (s), 1079 (m), 996 (s) cm . HRMS (EI):
+
+
22 4
calcd. for C20H O [M] 326.1518; found 326.1501.
4
MgSO , filtered, and concentrated under reduced pressure to give
(
E)-3-[4Ј-(Allyloxy)-6-(methoxymethoxy)-(1,1Ј-biphenyl)-3-yl]- compound 17 (23 mg, 0.07 mmol, 79%) in analytically pure form.
1
acrylaldehyde (15): Compound 14 (133 mg, 0.41 mmol) and MnO
532 mg, 6.12 mmol, 15 equiv.) were suspended in CH Cl (20 mL).
2
3
H NMR (500 MHz, CDCl ): δ = 9.67 (d, J = 7.7 Hz, 1 H), 7.52
(
2
2
(d, J = 2.2 Hz, 1 H), 7.50–7.44 (m, 2 H), 7.36 (dd, J = 8.4, 2.3 Hz,
1 H), 7.31 (d, J = 2.2 Hz, 1 H), 7.24 (d, J = 8.5 Hz, 1 H), 6.93 (d,
J = 8.4 Hz, 1 H), 6.66 (dd, J = 15.8, 7.8 Hz, 1 H), 6.03 (ddt, J =
The resulting mixture was stirred at ambient temperature for 12 h,
then filtered through a short pad of Celite, and concentrated under
reduced pressure. The residue was purified by column chromatog-
raphy on silica to furnish 15 (105 mg, 0.32 mmol, 79%). H NMR 3 H), 3.44 (s, 3 H), 3.43 (d, J = 6.1 Hz, 2 H) ppm. C NMR
16.7, 10.1, 6.7 Hz, 1 H), 5.12 (s, 2 H), 5.12–5.04 (m, 2 H), 3.81 (s,
1
13
(
300 MHz, CDCl
H), 7.29–7.23 (m, 1 H), 6.99 (d, J = 8.6 Hz, 2 H), 6.66 (dd, J = 131.3, 131.0, 129.7, 128.9, 128.5, 128.3, 128.1, 127.3, 115.8, 115.4,
5.8, 7.7 Hz, 1 H), 6.10 (ddt, J = 17.3, 10.6, 5.3 Hz, 1 H), 5.45 (dd, 110.1, 94.7, 56.5, 55.6, 34.3 ppm. IR (ATR): ν˜ = 2927 (br. m), 1673
J = 17.3, 1.0 Hz, 1 H), 5.32 (dd, J = 10.4, 0.6 Hz, 1 H), 5.20 (s, 2 (s), 1489 (s), 1245 (s), 1124 (s) cm . HRMS (EI): calcd. for
3
): δ = 9.68 (d, J = 7.7 Hz, 1 H), 7.55–7.41 (m, 5
3
(126 MHz, CDCl ): δ = 193.9, 156.9, 156.8, 152.8, 136.9, 132.3,
1
–
1
H), 4.60 (d, J = 5.2 Hz, 2 H), 3.43 (s, 3 H) ppm. 13C NMR
75 MHz, CDCl ): δ = 193.7, 158.3, 156.9, 152.6, 133.4, 132.2,
31.3, 130.6, 130.1, 128.0, 128.2, 127.4, 117.9, 115.6, 114.6, 94.9,
9.0, 56.5 ppm. IR (ATR): ν˜ = 1673 (s), 1490 (m), 1244 (s), 1125
+
+
21 22 4
C H O [M] 338.1518; found 338.1518.
(
1
6
3
4
Ј-Methoxymagnaldehyde B (3b): Compound 17 (20 mg,
0
.06 mmol) was dissolved in CH Cl /CF CO H (10:1, 2 mL), and
2
2
3
2
–1
+
+
the resulting mixture was stirred at ambient temperature for 2 h
and then diluted with ethyl acetate (50 mL). The mixture was
washed with brine (3ϫ 10 mL), and the organic layer was dried
(s), 983 (s) cm . HRMS (EI): calcd. for C20
20 4
H O [M] 324.1362;
found 324.1362.
(E)-3-[3Ј-Allyl-4Ј-hydroxy-6-(methoxymethoxy)-(1,1Ј-biphenyl)-3-yl-
with MgSO
4
, filtered, and concentrated under reduced pressure to
]
acrylaldehyde (16): Compound 15 (100 mg, 0.31 mmol) was dis-
furnish 3b (17 mg, 0.06 mmol, quantitative yield) in analytically
pure form. H NMR (300 MHz, CDCl ): δ = 9.63 (d, J = 7.8 Hz,
3
1
solved in N,N-diethylaniline (3 mL) in a vessel suited for microwave
irradiation. The closed vessel was placed in a microwave reactor
and irradiated at 250 °C for 1.0 h. The mixture was cooled to ambi-
ent temperature and diluted with ethyl acetate (50 mL). The re-
sulting solution was washed with hydrochloric acid (1.0 m, 3ϫ).
1 H), 7.54–7.45 (m, 3 H), 7.32 (dd, J = 8.3, 2.1 Hz, 1 H), 7.25 (d,
J = 1.9 Hz, 1 H), 7.05 (d, J = 8.2 Hz, 1 H), 7.01 (d, J = 8.4 Hz, 1
H), 6.67 (dd, J = 15.8, 7.9 Hz, 1 H), 6.03 (ddt, J = 16.8, 10.0,
6.7 Hz, 1 H), 5.57 (s, 1 H), 5.11 (ddd, J = 17.3, 3.2, 1.6 Hz, 1 H),
5.09 (ddd, J = 10.3, 2.8, 1.4 Hz, 1 H), 3.91 (s, 3 H), 3.46 (d, J =
The organic layer was dried with MgSO
under reduced pressure to yield compound 16 (57 mg, 0.18 mmol,
7%), which was sufficiently pure to be used in the next step with-
4
, filtered, and concentrated
1
3
3
6.6 Hz, 2 H) ppm. C NMR (75 MHz, CDCl ): δ = 194.7, 157.7,
5
156.1, 154.1, 136.4, 131.3, 130.5, 130.3, 129.7, 129.1, 128.0, 127.7,
1
out further purification. H NMR (300 MHz, CDCl
J = 7.7 Hz, 1 H), 7.53–7.44 (m, 3 H), 7.32–7.22 (m, 3 H), 6.89 (d, 3286 (br. w), 1657 (m), 1594 (s), 1497 (s), 1248 (m) cm
J = 8.1 Hz, 1 H), 6.66 (dd, J = 15.8, 7.7 Hz, 1 H), 6.06 (ddt, J =
1
2
(
1
1
(
[
3
): δ = 9.67 (d, 126.9, 126.4, 116.7, 116.2, 111.3, 55.7, 34.4 ppm. IR (ATR): ν˜ =
–
1
.
+
+
HRMS (EI): calcd. for C19
6.5, 10.1, 6.4 Hz, 1 H), 5.48 (s, 1 H), 5.27–5.13 (m, 2 H), 5.19 (s, 294.1263.
H), 3.47 (d, J = 6.4 Hz, 2 H), 3.44 (s, 3 H) ppm. 13C NMR
): δ = 194.0, 156.9, 153.9, 153.0, 136.4, 132.3,
H
18
O
3
[M] 294.1256; found
Dictyobiphenyl B (20): Compound 21 (68 mg, 0.30 mmol), com-
pound 7 (53 mg, 0.38 mmol, 1.30 equiv.), TBAF·3H O (372 mg,
.18 mmol, 4.0 equiv.), and Pd/C (10 wt.-%, 5.9 mg, 2 mol-%) were
75 MHz, CDCl
3
2
31.5, 131.3, 130.2, 129.0, 129.0, 128.1, 127.3, 125.4, 116.8, 115.7,
1
15.6, 94.8, 56.5, 35.2 ppm. IR (ATR): ν˜ = 1657 (s), 1597 (s), 1490
–
1
+
suspended in water (4.0 mL) in a vessel suited for microwave irradi-
ation. The closed vessel was placed in a microwave reactor and
irradiated at 150 °C for 0.5 h. After cooling to ambient tempera-
ture, KOH (132 mg, 2.36 mmol) was added, and the mixture was
irradiated again at 150 °C for 0.5 h. After cooling to ambient tem-
perature, the mixture was carefully acidified by the addition of hy-
drochloric acid (1.0 m). The resulting solution was extracted with
MTBE (3ϫ 50 mL). The combined organic layers were dried with
20 4
m), 1270 (m), 1131 (m) cm . HRMS (EI): calcd. for C20H O
+
M] 324.1362; found 324.1369.
Magnaldehyde B (3a): Compound 16 (28 mg, 0.09 mmol) was dis-
solved in CH Cl /CF CO H (10:1, 2 mL), and the resulting mix-
ture was stirred at ambient temperature for 2 h and then diluted
with ethyl acetate (50 mL). The mixture was washed with brine (3ϫ
2
2
3
2
1
4
0 mL), and the organic layer was dried with MgSO , filtered, and
concentrated under reduced pressure to furnish analytically pure
4
MgSO , filtered, and concentrated under reduced pressure. The res-
magnaldehyde B (3a, 24 mg, 0.09 mmol, quantitative yield); m.p.
idue was purified by column chromatography on silica (pure
1
1
1
1
6
52–155 °C. H NMR (300 MHz, CDCl
3
): δ = 9.60 (d, J = 7.8 Hz,
MTBE) to furnish dictyobiphenyl B (20, 59 mg, 0.26 mmol, 87%)
H), 7.53–7.42 (m, 3 H), 7.25–7.17 (m, 2 H), 7.03 (d, J = 8.2 Hz, as a colorless solid, m.p. 207 °C; ref.[ m.p. 208–210 °C. H NMR
44]
1
H), 6.95 (d, J = 8.8 Hz, 1 H), 6.65 (dd, J = 15.8, 7.9 Hz, 1 H),
.04 (ddt, J = 16.6, 10.1, 6.5 Hz, 1 H), 5.69 (s, 2 H), 5.18 (ddd, J
(300 MHz, [D
6
]acetone): δ = 7.96 (d, J = 2.2 Hz, 1 H), 7.84 (dd, J
= 8.4, 2.2 Hz, 1 H), 7.46 (d, J = 8.7 Hz, 2 H), 7.04 (d, J = 8.4 Hz,
1
3
=
3
17.3, 3.2, 1.6 Hz, 1 H), 5.17 (ddd, J = 10.3, 2.8, 1.6 Hz, 1 H),
6
1 H), 6.91 (d, J = 8.7 Hz, 2 H) ppm. C NMR (75 MHz, [D ]-
.47 (d, J = 6.4 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl
): δ = acetone): δ = 167.6, 159.3, 157.7, 133.2, 131.3, 130.8, 129.8, 129.3,
3
Eur. J. Org. Chem. 2015, 3760–3766
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3765

B. Schmidt, M. Riemer
FULL PAPER
1
23.1, 116.7, 115.9 ppm. IR (ATR): ν˜ = 3226 (br. s), 1679 (s), 1601
[21] J. Srinivas, P. P. Singh, Y. K. Varma, I. Hyder, H. M. S. Kumar,
Tetrahedron Lett. 2014, 55, 4295–4297.
–
1
+
(
10 4
s), 1516 (m), 1231 (s) cm . HRMS (EI): calcd. for C13H O
+
[22] M. Cui, H. S. Kim, Synlett 2012, 23, 311–313.
[M] 230.0579; found 230.0584.
[
[
[
23] W. Seo, S. Koo, K. Bae, Arch. Pharmacal Res. 1986, 9, 127–
130.
24] Y.-S. Kim, J.-Y. Lee, J. Park, W. Hwang, J. Lee, D. Park, Arch.
Pharmacal Res. 2010, 33, 61–65.
25] Y. Luo, Y. Xu, L. Chen, J. Hu, C. Peng, D. Xie, J. Shi, W.
Huang, G. Xu, M. Peng, J. Han, R. Li, S. Yang, Y. Wei, Bioorg.
Med. Chem. Lett. 2009, 19, 4702–4705.
Acknowledgments
The authors thank Evonik-Oxeno for generous donations of sol-
vents and Umicore for generous donations of precious metal cata-
lysts.
[26] L. Ma, J. Chen, X. Wang, X. Liang, Y. Luo, W. Zhu, T. Wang,
M. Peng, S. Li, S. Jie, A. Peng, Y. Wei, L. Chen, J. Med. Chem.
2
011, 54, 6469–6481.
[
[
1] S. Yahara, T. Nishiyori, A. Kohda, T. Nohara, I. Nishioka,
Chem. Pharm. Bull. 1991, 39, 2024–2036.
[27] M. Bernaskova, N. Kretschmer, W. Schuehly, A. Huefner, R.
Weis, R. Bauer, Molecules 2014, 19, 1223–1237.
2] Y. Fu, B. Liu, N. Zhang, Z. Liu, D. Liang, F. Li, Y. Cao, X.
Feng, X. Zhang, Z. Yang, J. Ethnopharmacol. 2013, 145, 193–
[28] W. Schühly, A. Hüfner, E. M. Pferschy-Wenzig, E. Prettner, M.
Adams, A. Bodensieck, O. Kunert, A. Oluwemimo, E.
Haslinger, R. Bauer, Bioorg. Med. Chem. 2009, 17, 4459–4465.
[29] B. Taferner, W. Schuehly, A. Huefner, I. Baburin, K. Wiesner,
G. F. Ecker, S. Hering, J. Med. Chem. 2011, 54, 5349–5361.
[30] S. Tripathi, M.-H. Chan, C. Chen, Bioorg. Med. Chem. Lett.
2012, 22, 216–221.
199.
[
[
[
[
[
3] W.-L. Kuo, C.-Y. Chung, T.-L. Hwang, J.-J. Chen, Phytochem-
istry 2013, 85, 153–160.
4] Y. Maruyama, H. Kuribara, M. Morita, M. Yuzurihara, S. T.
Weintraub, J. Nat. Prod. 1998, 61, 135–138.
5] M. Fujita, H. Itokawa, Y. Sashida, Chem. Pharm. Bull. 1972, [31] V. Praveen Kumar, R. Gajendra Reddy, D. D. Vo, S. Chakrav-
20, 212–213.
arty, S. Chandrasekhar, R. Grée, Bioorg. Med. Chem. Lett.
2012, 22, 1439–1444.
[32] V. Rempel, A. Fuchs, S. Hinz, T. Karcz, M. Lehr, U. Koetter,
C. E. Müller, ACS Med. Chem. Lett. 2013, 4, 41–45.
[33] U.-J. Youn, Q. C. Chen, W.-Y. Jin, I.-S. Lee, H.-J. Kim, J.-P.
Lee, M.-J. Chang, B.-S. Min, K.-H. Bae, J. Nat. Prod. 2007,
70, 1687–1689.
[34] U. Youn, Q. C. Chen, I. S. Lee, H. Kim, J.-K. Yoo, J. Lee, M.
Na, B.-S. Min, K. Bae, Chem. Pharm. Bull. 2008, 56, 115–117.
[35] U. J. Youn, N. Fatima, Q. C. Chen, S. Chae, T. M. Hung, B.-S.
Min, Phytother. Res. 2013, 27, 1419–1422.
6] S. I. Jeong, Y. S. Kim, M. Y. Lee, J. K. Kang, S. Lee, B. K.
Choi, K. Y. Jung, Pharmacol. Res. 2009, 59, 183–188.
7] F. Amblard, B. Govindarajan, B. Lefkove, K. L. Rapp, M. De-
torio, J. L. Arbiser, R. F. Schinazi, Bioorg. Med. Chem. Lett.
2007, 17, 4428–4431.
[
[
[
8] S. Arora, S. Singh, G. A. Piazza, C. M. Contreras, J. Panyam,
A. P. Singh, Curr. Mol. Med. 2012, 12, 1244–1252.
9] S.-Y. Lin, J.-D. Liu, H.-C. Chang, S.-D. Yeh, C.-H. Lin, W.-S.
Lee, J. Cell. Biochem. 2002, 84, 532–544.
10] H. Luo, Q. Zhong, L.-j. Chen, X.-r. Qi, A. f. Fu, H.-s. Yang,
F. Yang, H.-g. Lin, Y.-q. Wei, X. Zhao, J. Cancer Res. Clin. [36] T. Takeya, T. Okubo, S. Tobinaga, Chem. Pharm. Bull. 1987,
Oncol. 2008, 134, 937–945.
35, 1755–1761.
[11] E.-S. Hwang, K.-K. Park, Biosci. Biotechnol. Biochem. 2010,
[37] B. Schmidt, M. Riemer, M. Karras, J. Org. Chem. 2013, 78,
74, 961–967.
8680–8688.
[
[
12] J. Runeberg, Acta Chem. Scand. 1958, 12, 188–192.
[38] B. Schmidt, M. Riemer, J. Org. Chem. 2014, 79, 4104–4118.
[39] A. J. J. Lennox, G. C. Lloyd-Jones, Chem. Soc. Rev. 2014, 43,
412–443.
[40] C. Amatore, A. Jutand, G. Le Duc, Angew. Chem. Int. Ed.
2012, 51, 1379–1382.
[41] M. Butters, J. N. Harvey, J. Jover, A. J. J. Lennox, G. C. Lloyd-
Jones, P. M. Murray, Angew. Chem. Int. Ed. 2010, 49, 5156–
5160.
[42] S. W. Wright, D. L. Hageman, L. D. McClure, J. Org. Chem.
1994, 59, 6095–6097.
[43] D. Dallinger, C. O. Kappe, Chem. Rev. 2007, 107, 2563–2591.
[44] H. Kikuchi, Y. Matsuo, Y. Katou, Y. Kubohara, Y. Oshima,
Tetrahedron 2012, 68, 8884–8889.
[45] Sigma–Aldrich: http://sigmaaldrich.com (accessed August 28,
2014).
13] W. Gu, X. She, X. Pan, T.-K. Yang, Tetrahedron: Asymmetry
1
998, 9, 1377–1380.
14] H. Erhardt, T. Schlaeger, S. Heuser, Int. J. Appl. Chem. 2013,
, 177–184.
15] T. Takeya, T. Okubo, S. Tobinaga, Chem. Pharm. Bull. 1986,
4, 2066–2070.
16] T. Esumi, G. Makado, H. Zhai, Y. Shimizu, Y. Mitsumoto, Y.
Fukuyama, Bioorg. Med. Chem. Lett. 2004, 14, 2621–2625.
17] Z.-L. Kong, S.-C. Tzeng, Y.-C. Liu, Bioorg. Med. Chem. Lett.
[
[
[
[
9
3
2005, 15, 163–166.
[
[
18] C.-M. Chen, Y.-C. Liu, Tetrahedron Lett. 2009, 50, 1151–1152.
19] R. M. Denton, J. T. Scragg, J. Saska, Tetrahedron Lett. 2011,
52, 2554–2556.
[
20] B. V. Subba Reddy, R. Nageshwar Rao, N. Siva Senkar Reddy,
R. Somaiah, J. S. Yadav, R. Subramanyam, Tetrahedron Lett.
Received: March 16, 2015
Published Online: May 5, 2015
2014, 55, 1049–1051.
3766
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