Total Synthesis of the Natural Pyridocoumarins Goniothaline A and B

Article abstract of DOI:10.1055/s-0037-1610909

In this paper, we report the first total synthesis of goniothaline A and B, which are rare natural pyridocoumarins isolated from Goniothalamus australis. The key feature of the synthesis of goniothaline A is high-yielding silver-catalyzed cycloisomerization to afford the pyridine moiety. In addition, goniothaline B, a natural 8-hydroxyquinoline derivative, is readily synthesized by the regioselective demethylation of goniothaline A.

Full text of DOI:10.1055/s-0037-1610909

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
©
Georg Thieme Verlag Stuttgart · New York
2018, 50, A–E
paper
A
en
Synthesis
S. Ahn et al.
Paper
Total Synthesis of the Natural Pyridocoumarins Goniothaline A
and B
Sungwan Ahn
Perkin reaction
Jeong A Yoon
OMe
O
Young Taek Han*
OR
N
OH 7 steps
Goniothaline A, R = Me (1)
Goniothaline B, R = H (2)
H
College of Pharmacy, Dankook University,
Dandae-ro 119, Cheonan 31116, Republic of Korea
hanyt@dankook.ac.kr
O
O
HO
Selective
demethylation
Silver-catalyzed
cycloisomerization
Received: 30.07.2018
Accepted after revision: 23.08.2018
Published online: 17.09.2018
ture of 1 and 2 prompted us to investigate an efficient syn-
thetic method that can be used in subsequent medicinal
chemistry research.
DOI: 10.1055/s-0037-1610909; Art ID: ss-2018-f0509-op
Abstract In this paper, we report the first total synthesis of gonio-
thaline A and B, which are rare natural pyridocoumarins isolated from
Goniothalamus australis. The key feature of the synthesis of goniothaline
A is high-yielding silver-catalyzed cycloisomerization to afford the pyri-
dine moiety. In addition, goniothaline B, a natural 8-hydroxyquinoline
derivative, is readily synthesized by the regioselective demethylation of
goniothaline A.
privileged structures
in goniothalines
OMe
O
O
5
6
OR
coumarin
OH
O
2
O
N
Key words total synthesis, goniothaline, Perkin reaction, silver-cata-
lyzed cycloisomerization, selective demethylation
8
10
N
Goniothaline A, R = Me (1)
Goniothaline B, R = H (2)
8-hydroxyquinoline
Coumarins, including heterocycle-linked and fused cou-
marins, have been reported to possess diverse biological ac-
tivities and hence are regarded as privileged scaffolds in
Figure 1 Structure of goniothaline A (1) and B (2), and embedded
privileged structures
1
drug discovery. Consequently, much effort has devoted to
not only acquire diverse natural and non-natural com-
pounds bearing novel coumarin skeletons, but also develop
efficient synthetic methods thereof.
The retrosynthetic analysis for goniothalines is depicted
in Scheme 1, which includes the efficient construction of
the 5,6-dimethoxy-10-methylpyridocoumarin skeleton. Go-
niothaline B (2), a 5-hydroxy-6-methoxypyridocoumarin,
was anticipated to be derived from goniothaline A (1) via
selective demethylation of its 6-methoxy group, by the di-
2
Goniothaline A (1) and B (2) are unprecedented natural
pyridocoumarin derivatives isolated from Goniothalamus
3
australis, an Australian rainforest plant (Figure 1). Gonio-
thaline A (1) possesses two methoxy groups at the 5- and 6-
positions, whereas goniothaline B (2) has a hydroxy group
instead of the methoxy group at the 6-position. The 8-hy-
droxyquinoline (8-HQ) moiety found in 2 has been consid-
5
recting effect of the neighboring pyridine nitrogen. 5,6-Di-
methoxy-10-methylpyridocoumarin 1 was expected to be
synthesized from 7-amino-5,6-dimethoxycoumarin 3 via
synthetic methodologies for quinoline moiety such as the
Skraup–Doebner–Miller reaction, Povarov reaction, or di-
verse metal-catalyzed reactions.6
Further, it was anticipated that 3 can be readily pre-
pared from 6-hydroxy-5-methoxycoumarin 4 via regio-
selective nitration, O-methylation, and reduction of the ni-
tro group. Hydroxycoumarin 4 could be accessed by cop-
4
ered as a privileged scaffold, as many 8-HQs show thera-
peutically beneficial activities against neurodegenerative
diseases, cancers, infective diseases, etc., by virtue of their
4b
metal-chelating properties. Goniothalines are expected to
exhibit a diverse range of biological activities because of the
6-hydroxypyridocoumarin skeleton embedded with the
privileged scaffolds coumarin and 8-HQ. The unique struc-
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–E

B
Synthesis
S. Ahn et al.
Paper
without the formation of the regioisomer 8-nitrocoumarin.
The structure of 7 was confirmed by combined 2D-NMR
analysis (see Supporting Information). We also could obtain
7 under in situ nitronium generation conditions, i.e., by us-
ing a combination of NaNO and KHSO in the presence of
OMe
OMe
OH
N
OMe
N
O
O
O
O
3
4
wet silica,1
1b,c
although the yield did not exceed 52%. Fur-
2
1
11d
OMe
OMe
ther, we found that cerium ammonium nitrate (CAN) and
OMe
OH
11e
nitric acid were unsuitable for the generation of 7 from 4.
Williamson etherification of 7 readily afforded dimethoxy-
coumarin 8, which was subjected to nitro reduction using
O
O
O
NH2
OH
O
O
3
4
SnCl to provide 7-aminocoumarin 3, a key intermediate for
2
constructing the pyridocoumarin skeleton of goniothalines.
With 3 in hand, we first attempted the Doebner–Miller
reaction, an acid-catalyzed one-pot method for synthesiz-
ing quinoline from anilines and α,β-unsaturated carbonyl
compounds.12 When 3 was refluxed with methyl vinyl ke-
H
HO
5
Scheme 1 Retrosynthetic analysis of goniothaline A (1) and B (2)
12b
tone in concentrated HCl or AcOH in the presence of Fe-
12c
Cl3, a mixture of unidentifiable products was obtained,
possibly due to the acid-labile nature of the coumarin moi-
ety.6a Therefore, we conceived a stepwise route via silver-
per-catalyzed oxidative methoxylation7 and subsequent
coumarin synthesis from the commercially available 2,5-di-
hydrobenzaldehyde (5).
As shown in Scheme 2, our synthesis commenced with
the preparation of previously reported 3,6-dihydroxy-2-
13
catalyzed cycloisomerization, as shown in Scheme 3. To
prepare 7-(but-2-ynylamino)coumarin 9, 1-bromobut-2-
yne was added portionwise to the refluxing solution of 7-
aminocoumarin 3 and K CO in anhydrous acetone. Then, 9
methoxybenzaldehyde (6) by copper-catalyzed oxidative
methoxylation.
2
3
7
2,5-Dihydroxybenzaldehyde (5) was
was isolated in 66% yield (84% yield brsm) along with the
stirred with CuCl and CaSO under O atmosphere to obtain
a 2-methoxybenzoquinone intermediate that was subjected
unreacted 3 (20%) and dialkynylated byproduct (11%). Cy-
4
2
13
cloisomerization of 9 using a catalytic amount of AgSbF6
afforded the desired goniothaline A (1) in high yield (98%).
to reduction with Na S O to provide hydroquinone 6. This
2
2
4
1
13
unstable compound was immediately used in the next step
without further purification. Several sets of reaction condi-
The H and C NMR data of 1 were in agreement with those
3
of the natural product. We hypothesized that the nitrogen
tions were investigated for the synthesis of coumarin 4.
atom at the 7-position of 1 would serve as a directing group
8
Perkin reaction of o-hydroxybenzaldehyde 6 using Ac O
for the selective cleavage of the methyl ether at the 6-posi-
2
5
and NaOAc afforded coumarin 4 in the best yield (51%).
tion to furnish goniothaline B (2). As expected, 2 was ob-
9
Knoevenagel condensation (with Meldrum’s acid) and Wit-
tained in high yield (92%) by refluxing 1 with 3 equiv of BCl3
in CH Cl for 4 hours. The spectral data of 2 were also con-
10
tig olefination of 6 also gave 4, but the yields decreased
slightly to 47%.
2
2
sistent with the previously reported data.3
Next, to introduce a nitrogen moiety at the 7-position of
-hydroxycoumarin 4, we carried out nitration using sever-
In summary, the first total synthesis of the natural
pyridocoumarins, goniothaline A (1) and B (2), has been ac-
complished. Aminocoumarin 3 was prepared in moderated
yield after intensive optimization of the nitration condition
for hydroxycoumarin 4. The key feature of the synthesis of 1
6
al reported reaction conditions for the regioselective ortho-
11
nitration of phenolic compounds. When 4 was refluxed
with 1.2 equiv of NH NO and 1 equiv of KHSO in acetoni-
4
3
4
1
1a,b
trile,
7-nitrocoumarin 7 was obtained in best yield (67%)
O
O
OMe
OMe
NH4NO3
NaOAc
Ac2O
CuCl, MeOH
CaSO4, O2
OH
OH
OH
KHSO4
H
H
MeCN
reflux
MeCN
DMF
HO
HO
O
O
180 °C
0
°C
5
71%
6
51%
4
67%
OMe
OMe
OMe
MeI
Cs2CO3
OH
OMe
SnCl2
OMe
NH2
DMF
r.t.
EtOH
70 °C
O
O
NO2
O
O
NO2
O
O
7
87%
8
86%
3
Scheme 2 Preparation of 7-aminocoumarin intermediate 3
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–E

C
Synthesis
S. Ahn et al.
Paper
6
-Hydroxy-5-methoxy-2H-chromen-2-one (4)
Br
OMe
OMe
To a solution of benzaldehyde 6 (127 mg, 0.76 mmol) and NaOAc (186
mg, 2.27 mmol) in DMF (1.3 mL) was added Ac O (0.29 mL, 3.02
mmol, 4.0 equiv) at r.t. The mixture was stirred at 180 °C for 3 h and
then allowed to cool to r.t., diluted with EtOAc, and quenched with 1
M HCl. The organic layer was washed with 1 M HCl and brine, dried
OMe
OMe
NH2
K2CO3
2
acetone
O
O
N
H
O
O
reflux
66%
3
9
(
MgSO ), and concentrated in vacuo. Purification of the residue via
4
flash column chromatography (silica gel, EtOAc/5% CH Cl in n-hex-
ane 1:5 to 1:2) afforded chromenone 4 (74 mg, 51%) as a yellow solid;
Rf = 0.2 (EtOAc/n-hexane 1:2).
2
2
OMe
OMe
OMe
N
OH
N
AgSbF6
BCl3
IR (neat): 3289, 1685, 1573, 1312, 1074 cm–1
.
O
O
O
O
MeCN
reflux
CH2Cl2
reflux
1
H NMR (500 MHz, CDCl ): δ = 7.92 (d, J = 9.8 Hz, 1 H), 7.16 (d, J = 9.0
3
Hz, 1 H), 7.04 (d, J = 9.0 Hz, 1 H), 6.44 (d, J = 9.7 Hz, 1 H), 3.93 (s, 3 H).
98%
1
92%
2
13
C NMR (125 MHz, CDCl ): δ = 161.0, 147.3, 145.8, 142.8, 136.6,
3
Scheme 3 Completion of the synthesis of goniothaline A (1) and B (2)
120.9, 115.6, 113.7, 111.8, 61.6.
HRMS (Q-ToF): m/z [M + H]+ calcd for C10H O : 193.0495; found:
193.0499.
9
4
is the silver-catalyzed isomerization. Unlike acid-catalyzed
one-pot quinoline synthesis methods, our synthetic route
provided the pyridocoumarin skeleton without decomposi-
tion of the acid labile 3. In addition, 8-HQ derivative 2 was
successfully synthesized from 1 via regioselective demeth-
ylation by the neighboring pyridine nitrogen. Because of its
high efficiency, this synthesis protocol can be extended to
various structurally related pyridocoumarins. Further syn-
thesis of analogues and biological studies are in good prog-
ress in our laboratory, and the results will be reported in
due course.
6-Hydroxy-5-methoxy-7-nitro-2H-chromen-2-one (7)
To a solution of hydroxychromenone 4 (200 mg, 1.04 mmol) in MeCN
(17 mL) were added NH
NO (100 mg, 1.25 mmol, 1.2 equiv) and KH-
4
3
SO (142 mg, 1.04 mmol, 1.0 equiv) at r.t. The mixture was stirred for
4
30 min at this temperature, then it was heated at reflux for 19 h. The
mixture was filtered through celite, and the filtercake was washed
with MeCN and CH Cl . The combined filtrate and washes were con-
2
2
centrated in vacuo. Purification of the residue via flash column chro-
matography (silica gel, EtOAc/5% CH Cl in n-hexane 1:5 to 1:3) af-
2
2
forded nitrochromenone 7 (166 mg, 67%) as a yellow solid; R = 0.3
f
(EtOAc/n-hexane 1:2).
IR (neat): 1763, 1532, 1466, 1290 cm–1
.
Unless noted otherwise, all starting materials and reagents were ob-
tained commercially and were used without further purification. All
solvents utilized for routine product isolation and chromatography
were of reagent grade and glass-distilled, and reaction flasks were
dried at 100 °C before use. Flash column chromatography was per-
formed using silica gel 60 (230–400 mesh, Merck) with the indicated
solvents. TLC was performed using 0.25-mm silica gel plates (Merck).
Mass spectra were obtained using an Agilent 6530 Q-TOF unit. Infra-
1
H NMR (500 MHz, CDCl ): δ = 10.47 (s, 1 H), 8.03 (d, J = 9.8 Hz, 1 H),
.83 (s, 1 H), 6.57 (d, J = 9.8 Hz, 1 H), 4.12 (s, 3 H).
3
7
13
C NMR (125 MHz, CDCl ): δ = 159.2, 146.1, 145.3, 144.7, 137.0,
3
1
35.2, 120.5, 120.3, 106.7, 62.2.
HR-MS (Q-ToF): m/z [M + H]+ calcd for C10H NO : 238.0346; found:
2
8
6
38.0350.
1
13
red spectra were recorded on a FT-IR spectrophotometer. H and
C
5,6-Dimethoxy-7-nitro-2H-chromen-2-one (8)
spectra were recorded on a Bruker Analytik AVANCE digital 400 (400
MHz) and AVANCE digital 500 (500 MHz) spectrometer in CDCl3,
To a solution of hydroxychromenone 7 (100 mg, 0.42 mmol) and Cs2-
CO3 (647 mg, 2.11 mmol, 5.0 equiv) in DMF (2 mL) was added MeI
(0.13 mL, 2.11 mmol, 5.0 equiv) at r.t. The mixture was stirred for 2 h
at this temperature, and then it was diluted with EtOAc and quenched
with water. The organic layer was washed with 1 M HCl and brine,
CD OD, DMSO-d and are referenced to the deuterated solvent.
3
6
6-Hydroxy-5-methoxy-2H-chromen-2-one (4)
dried (MgSO ), and concentrated in vacuo. Purification of the residue
4
via flash column chromatography (silica gel, EtOAc/2% CH Cl2 in n-
hexane 1:4 to 1:3) afforded dimethoxychromenone 8 (92 mg, 87%) as
3
,6-Dihydroxy-2-methoxybenzaldehyde (6)
2
To a solution of 2,5-dihydroxybenzaldehyde (5; 1.0 g, 7.24 mmol) in
MeCN (29 mL) were added MeOH (2.2 mL, 54.3 mmol, 7.5 equiv), an-
hyd CaSO (14.49 g, 106.43 mmol, 14.7 equiv), and CuCl (3.58 g, 36.2
a yellow solid; R = 0.4 (EtOAc/n-hexane 1:2).
f
IR (neat): 1766, 1574, 1521, 1415, 1352 cm–1
.
4
mmol, 5.0 equiv) at r.t. The mixture was stirred vigorously under an
1
H NMR (500 MHz, CDCl ): δ = 8.01 (d, J = 9.7 Hz, 1 H), 7.45 (s, 1 H),
3
O atmosphere at 0 °C for 7 h. To the mixture was added an aq soln of
2
6.53 (d, J = 9.7 Hz, 1 H), 4.07 (s, 3 H), 3.99 (s, 3 H).
13
NaHCO and Na S O (83 mL; NaHCO : 1.46 g, 17.38 mmol; Na S O :
3
2
2
4
3
2
2
4
C NMR (125 MHz, CDCl ): δ = 159.3, 151.0, 149.2, 146.4, 142.3,
3
7.18 g, 41.27 mmol) at 0 °C, and then it was allowed to warm up to r.t.
1
37.2, 118.9, 117.6, 107.8, 62.6, 62.2.
The mixture was stirred for 12 h at r.t. and then diluted with EtOAc.
The organic layer was washed with water and brine, dried (MgSO4),
and concentrated in vacuo to give methoxybenzaldehyde 6 (862 mg,
HR-MS (Q-ToF): m/z [M + H]+ calcd for C11H10NO : 252.0503; found:
2
6
52.0508.
71%) as a yellow solid, which was used without further purification
for next reaction step.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–E

D
Synthesis
S. Ahn et al.
Paper
7
-Amino-5,6-dimethoxy-2H-chromen-2-one (3)
Goniothaline B (2)
To a solution of goniothaline A (1; 10 mg, 0.37 mmol) in CH Cl (1.8
To a solution of nitrochromenone 8 (100 mg, 0.40 mmol) in EtOH (4
2
2
mL) was added SnCl (380 mg, 2.0 mmol, 5.0 equiv), and the mixture
mL) was added 1.0 M BCl in CH Cl (0.11 mL, 0.11 mmol, 3 equiv) at
2
3 2 2
was heated at 70 °C for 3 h. The mixture was cooled to r.t. and poured
0 °C. The mixture was heated to reflux for 4 h, and then it was
cooled to r.t. and quenched with water. The organic layer was
onto an ice/water mixture which was basified with NaHCO until pH
3
8
–9. The aqueous layer was extracted with EtOAc several times. The
combined organic layers were washed with water and brine, dried
MgSO ), filtered, and concentrated in vacuo. Purification of the resi-
washed with water, brine, dried (MgSO ), filtered, and concentrated
in vacuo. Purification of the residue via flash column chromatogra-
4
(
phy (silica gel, Et O/CH Cl 1:10 to 1:5) afforded goniothaline B (2;
4
2
2
2
due via flash column chromatography (silica gel, EtOAc/1% CH Cl in
8.7 mg, 92%) as a light-brown gum; R = 0.2 (Et O/CH Cl 1:6). The
2
2
f 2 2 2
n-hexane 1:3 to 1:1) afforded aminochromenone 3 (78 mg, 86%) as a
spectral data were consistent with that previously reported.
yellow solid; R = 0.25 (EtOAc/n-hexane 1:1).
IR (neat): 3349, 1714, 1303, 1079 cm–1
f
.
IR (neat): 3356, 1715, 1623, 1259 cm–1
.
1
H NMR (400 MHz, DMSO-d ): δ = 9.65 (br s, 1 H), 8.80 (d, J = 4.1 Hz, 1
6
1
H NMR (500 MHz, CDCl ): δ = 7.85 (d, J = 9.6 Hz, 1 H), 6.39 (s, 1 H),
H), 8.28 (d, J = 9.7 Hz, 1 H), 7.48 (d, J = 4.1 Hz, 1 H), 6.62 (d, J = 9.5 Hz,
3
6.10 (d, J = 9.6 Hz, 1 H), 4.4 (s, 2 H), 3.97 (s, 3 H), 3.85 (s, 3 H).
1 H), 4.03 (s, 3 H), 2.99 (s, 3 H).
13
13
C NMR (125 MHz, CDCl ): δ = 162.0, 152.3, 149.0, 145.2, 139.2,
C-NMR (125 MHz, DMSO-d ): δ = 159.6, 149.8, 145.5, 144.5, 141.2,
3
6
136.0, 110.3, 105.3, 96.9, 61.5, 60.4.
139.8, 139.7, 137.8, 124.0, 115.5, 114.9, 112.1, 60.9, 23.5.
HR-MS (Q-ToF): m/z [M + H]+ calcd for C11H12NO : 222.0761; found:
HR-MS (Q-ToF): m/z [M + H]+ calcd for C14H12NO : 258.0761; found:
4
4
222.0766.
258.0765.
7-(But-2-ynylamino)-5,6-dimethoxy-2H-chromen-2-one (9)
Funding Information
To a solution of aminochromenone 3 (10 mg, 0.045 mmol) and K CO
2
3
(
14.4 mg, 0.104 mmol, 2.3 equiv) in acetone (0.4 mL) was added 1-
This work was supported by the National Research Foundation of Ko-
rea (NRF) grant funded by the Ministry of Science, ICT & Future Plan-
bromobut-2-yne (6 mg, 0.045 mmol, 1 equiv) at r.t., and then the
mixture was heated to reflux. After 19 h, 1-bromobut-2-yne (6 mg,
0
ning (NRF-2017R1C1B1001826).
N
oaitn
a
l
Research
F
o
u
n
d
oaitn
of
K
ore
a
N( RF-2
0
1
7
R
1
C
1
B
1
0
0
1
8
2
6)
.045 mmol, 1 equiv) was added to the mixture, and it was stirred for
a further 30 h at the same temperature. The mixture was cooled to
r.t., and then it was filtered and concentrated in vacuo. Purification of
the residue via flash column chromatography (silica gel, EtOAc/4%
CH Cl in n-hexane 1:5 to 1:2) afforded 7-(but-2-ynylamino)chrome-
Supporting Information
2
2
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610909.
none 9 (8.2 mg, 66%) as a yellow gum along with unreacted 3 (2.0 mg,
0%) and dialkynylated byproduct (1.6 mg, 11%); R = 0.3 (EtOAc/n-
S
u
p
p
o
nrtogI
i
f
rm oaitn
S
u
p
p
ortioIgnfmr oaitn
2
f
hexane 1:2).
IR (neat): 1719, 1611, 1258, 772 cm–1
.
References
1
H NMR (500 MHz, CDCl ): δ = 7.85 (d, J = 9.5 Hz, 1 H), 6.39 (s, 1 H),
3
(
1) (a) Grover, J.; Jachak, S. M. RSC Adv. 2015, 5, 38892. (b) Jameel,
E.; Umar, T.; Kumar, J.; Hoda, N. Chem. Biol. Drug Des. 2016, 87,
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3.84 (s, 3 H), 1.83–1.82 (m, 3 H).
2
13
C NMR (125 MHz, CDCl ): δ = 162.2, 152.8, 148.1, 145.2, 139.2,
3
Dehahan, G.; Alizadeh, B. H.; Ramazani, A.; Ardestani, S. K.;
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Rep. 2015, 32, 1472.
135.9, 109.9, 104.6, 93.7, 61.5, 60.5, 33.45, 29.85, 14.29, 3.72.
HR-MS (Q-ToF): m/z [M + H]+ calcd for C15H16NO : 274.1074; found:
4
274.1078.
(
2) (a) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003,
Goniothaline A (1)
103, 893. (b) Nicolaou, K. C.; Pfefferkorn, J. A.; Roecker, A. J.; Cao,
To a solution of 7-(but-2-ynylamino)chromenone 9 (10 mg, 0.037
mmol) in MeCN (1 mL) was added AgSbF6 (1.0 mg, 3.7 μmol, 0.1
equiv) at r.t. The mixture was refluxed for 5 h, and then concentrated
in vacuo. Purification of the residue via flash column chromatography
G.-Q.; Barluenga, S.; Mitchell, H. J. J. Am. Chem. Soc. 2000, 122,
9939. (c) Symeonidis, T. S.; Litinas, K. E. Tetrahedron Lett. 2013,
54, 6517. (d) Belal, M.; Das, D. K.; Khan, A. T. Synthesis 2015, 47,
1109.
(
silica gel, Et O/CH Cl 1:20 to 1:10) afforded goniothaline A (1; 9.7
2 2 2
(
3) Levrier, C.; Balastrier, M.; Beattle, K. D.; Carroll, A. R.; Martin, F.;
Choomuenwai, V.; Davis, R. A. Phytochemistry 2013, 86, 121.
4) (a) Oliveri, V.; Vecchio, G. Eur. J. Med. Chem. 2016, 120, 252.
mg, 98%) as a light-brown gum; R = 0.1 (Et O/CH Cl 1:20). The spec-
tral data were consistent with that previously reported.
IR (neat): 1731, 1622, 1367, 1226, 1083, 1039 cm–1
f
2
2
2
(
.
(b) Song, Y.; Xu, H.; Chen, W.; Zhan, P.; Liu, X. Med. Chem.
1
H NMR (500 MHz, DMSO-d ): δ = 8.83 (d, J = 4.4 Hz, 1 H), 8.28 (d, J =
Commun. 2015, 6, 61.
6
9
.7 Hz, 1 H), 7.44 (d, J = 4.4 Hz, 1 H), 6.63 (d, J = 9.8 Hz, 1 H), 4.10 (s, 3
(5) (a) Pettit, G. R.; Hoffmann, H.; Herald, D. L.; McNulty, J.;
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H), 4.00 (s, 3 H), 2.97 (s, 3 H).
13
C-NMR (125 MHz, DMSO-d ): δ = 159.4, 151.1, 148.5, 146.3, 145.5,
6
2251. (b) Ahn, S.; Han, Y. T. Tetrahedron Lett. 2017, 58, 4779.
145.4, 142.2, 139.7, 123.9, 115.8, 115.4, 111.5, 62.0, 61.9, 23.7.
(
6) (a) Khusnutdinov, R. I.; Bayguzina, A. R.; Dzhemilev, U. M.
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HR-MS (Q-ToF): m/z [M + H]+ calcd for C15H14NO : 272.0917; found:
4
272.0919.
24463.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–E

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Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–E