Synthesis of non-symmetrical 3,4-diaryl-substituted pyrroles: Implementation for the preparation of lamellarin R

Article abstract of DOI:10.3184/174751917X15105690662863

A straightforward method for synthesising symmetrical and non-symmetrical 3,4-diaryl-substituted pyrroles is proposed, consisting of (i) the condensation reaction between phenylacetonitriles and aldehydes to give acrylonitriles, (ii) the conjugate additio

Full text of DOI:10.3184/174751917X15105690662863

JOURNAL OF CHEMICAL RESEARCH 2017
VOL. 41 DECEMBER, 677–683
RESEARCH PAPER 677
Synthesis of non-symmetrical 3,4-diaryl-substituted pyrroles: implementation
for the preparation of lamellarin R
Héctor Zavala-Gómez, Armando Ramírez-Rodríguez and Alfredo Vázquez*
Departamento de Química Orgánica, Facultad de Química, Universidad Nacional Autónoma de México, Circuito Interior S/N, Ciudad Universitaria, 04510,
CDMX, México
A straightforward method for synthesising symmetrical and non-symmetrical 3,4-diaryl-substituted pyrroles is proposed, consisting of
(i) the condensation reaction between phenylacetonitriles and aldehydes to give acrylonitriles, (ii) the conjugate addition of cyanide to
afford succinonitriles, and (iii) reduction of the succinonitriles with DIBAL-H to provide the target pyrroles in good overall yields. The
implementation of this technology for the preparation of lamellarin R is presented.
Keywords: heterocyclic compounds, pyrroles, lamellarins, N-arylation of pyrroles, natural products
In recent years, an increasing number of alkaloids with
different molecular architectures containing a pyrrole ring
have been isolated from marine organisms,1–3 mainly from
ascidians and sponges, as well as from other sources.4 Among
these natural products, lamellarins (Fig. 1) are an important
group of pyrrole-containing compounds first isolated by
Faulkner in 1985 from the marine mollusc Lamellaria sp.5
Since the isolation of lamellarins A–D, an increasing number
of structurally related compounds have been reported.6 For
instance, in 1988 lamellarins E–H were isolated from the marine
ascidian Didemnum chartaceum.7 In 1992, the structurally
related compounds lukianol A and B were recovered from
an unidentified tunicate,8 and in 1993 lamellarins I–N were
reported from an Australian colonial ascidian Didemnum sp.9
Later, in 1994, lamellarins O and P,10 and in 1995, lamellarins
Q and R11 were obtained from different geographically
located specimens of the marine sponge Dendrilla cactos.
Currently, more than 70 different lamellarins and structurally
related 3,4-diaryl-substituted pyrrole-derived compounds,
isolated from diverse marine organisms, have been reported.
Remarkably, a significant number of the members of this group
of alkaloids exhibit different kinds of biological activities,
including antitumour,12 reversal of multidrug resistance (MDR),
antiviral and HIV inhibition.13 Until now, lamellarin D has
been the most studied and promising member of this family of
compounds.14–17
Fig. 1. Structures of lamellarins D, N, O, R and lukianol A.
All lamellarins possess aryl substituents at C-3 and C-4 of
the pyrrole moiety, and they can be classified into three groups
according to their structural features. In the first group, the
central pyrrole ring is unfused. In the second group, the pyrrole
moiety is fused to an isoquinoline ring with an unsaturated
C5–C6 bond, whereas in the third group the pyrrole contains a
quinoline ring with a saturated C5–C6 bond.18,19
In recent decades, different approaches have been reported
for the synthesis of lamellarins.6,19,20 For instance, 10 years
after the isolation of lamellarins A–D, Fürstner and co-
workers21 employed the reductive cleavage of the N–O bond of
a 2,3-diarylisoxazole, followed by a McMurry cyclisation as
the fundamental transformation, to accomplish the first total
synthesis of the O-dimethyl ether of lamellarin O. Starting
from this compound, they were able to obtain lamellarin O and
lukianol A. Similarly, Boger reported the synthesis of lamellarin
O using an elegant aza-Diels-Alder strategy combining a
1,2,4,5-tetrazine and a 1,2-diaryl acetylene22. Several subsequent
syntheses of non-fused pyrrole lamellarins focused instead on
lamellarin Q dialkyl ethers as the key intermediate for further
transformations. Examples include the works of Banwell23
on the synthesis of lamellarin O, Alvarez24 for lamellarine
Q, and Iwao25 for lamellarins P and R by constructing the
pyrrole nucleus first, followed by the introduction of the phenyl
rings using cross-coupling procedures.26-28. More recently,
our group used a Paal–Knorr approach for the preparation
of 3,4-disubstitued pyrroles starting from succinonitriles as
1,4-dicarbonyl precursors (Scheme 1). Thus, we were able to
prepare lamellarins Q and O quite easily.29
The wide variety of biological activities displayed by
lamellarins continues to elicit the interest of synthetic chemists
in developing new and more efficient methodologies for
obtaining these compounds in the quantities required for
extensive biological studies. Herein, we disclose the scope of our
previously reported methodology, as well as its implementation,
by making a series of non-symmetrical 3,4-diarylpyrroles in
combination with a copper-catalysed cross-coupling reaction in
a new synthesis of lamellarin R.
* Correspondent. E-mail: joseavm@unam.mx

678 JOURNAL OF CHEMICAL RESEARCH 2017
R3
R3
R3
R1
R3
1.DIBAL
2.NaH2PO4
NC
NC
R2
NC
-CN
R2
R1
R2
R1
+
NaOMe
CHO
CN
R2
10
7
N
H
R1
6
8
9
Scheme 1 Methodology for the synthesis of non-symmetrical 3,4-diaryl-substituted pyrroles.
Results and discussion
Finally, treatment of succinonitriles 9b–h with
diisobutylaluminium hydride (DIBAL) (2.5 equiv) followed by
aqueous NaH2PO4 afforded the desired pyrroles in good overall
yields (Table 3).
After proving the generality of our method, we explored the
functionalisation of the N atom in the pyrrole ring. Base on
a report by Buchwald and co-workers, where they performed
copper-mediatedcross-couplingsbetweenN–Hheterocyclesand
aromatic iodides in the presence of diamine ligands in excellent
yields,32 we explored the arylation of 3,4-diphenylpyrrole
12 using commercially available 4-iodoanisole under
Buchwald’s conditions (Scheme 3). In our first experiment,
ethylenediamine, an inexpensive ligand for this reaction, was
From a general viewpoint, two approaches can be envisioned
for the synthesis of a heterocyclic compound: (i) modification
on an existing heterocyclic ring, usually through substitution
reactions, and (ii) synthesis of the heterocyclic core from an
acyclic precursor.29 Even though pyrroles undergo electrophilic
substitution in a straightforward manner, this process takes
place preferentially or exclusively at C2/C5, and some additional
manipulations might be required to introduce substituents
selectively at C3/C4 (e.g. introduction of a triisopropylsilyl
ether (TIPS) protecting group at the nitrogen atom).30
Knoevenagel
condensation
between
benzaldehyde
reported
and phenylacetonitriles 6a–h, according to
a
methodology,29 afforded the desired acrylonitrile derivatives
8a–h, in a straightforward fashion (Table 1, entries 2–8).
However, the reaction between (4-nitrophenyl)acetonitrile and
benzaldehyde did not occur under the conditions mentioned
above (sodium methoxide, 1.2 equiv. in methanol), leading
only to complete consumption of (nitrophenyl)acetonitrile,
presumably due to the high stability of the corresponding anion.
To overcome this obstacle, acrylonitrile 8a was prepared using
K3PO4 as a solid basic catalyst, as reported by Saad31 (Table
1, entry 1). For the formation of succinonitriles, we used
standard conditions (KCN/NH4Cl; DMF/H2O). Unfortunately,
nitroacrylonitrile 8a did not react to form succinonitrile 9a,
and compound 11 was the only isolated product (Table 2, entry
1). We believe that compound 11 might be formed by a formal
redox reaction. Experiments to investigate the mechanism for
this transformation are currently underway, and the results will
be published elsewhere.
NO2
NC
NO2
CN
NC
9a
Not formed
NH2
8a
NC
CN
11
Isolated
Scheme 2 Formal redox reaction of 8a.
Table 2 Michael addition of cyanide to obtain succinonitriles
Table 1 Knoevenagel condensation
R3
R3
R3
R3
NaOMe,
methanol,
reflux 6 to 8 h.
NC
NC
R2
NC
NC
2.5
KCN,
eq.
1.5 eq. NH4Cl
R2
R1
R2
R1
R2
R1
+
CHO
CN
7
3:1 DMF/H
80 °C
2O
R1
8
9
6
8
R1
NO2
Cl
Me
OMe
H
NMe2
NBn2
NBn2
R2
H
H
H
H
OMe
H
H
R3
H
H
H
H
H
H
H
Cl
Product
8a
8b
8c
8d
8e
8f
8g
8h
Yield (%)
91
95
95
87
98
84
98
95
Entry
R1
NO2
Cl
Me
OMe
H
NMe2
NBn2
NBn2
R2
H
H
H
H
OMe
H
H
R3
H
H
H
H
H
H
H
Cl
Product
9a
9b
9c
9d
9e
9f
9g
9h
Yield (%)
Entry
1a
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
ND
86
89
89
79
94
90
92
H
H
a4 equiv. of K3PO4 were used as the base.
ND, not determined.

JOURNAL OF CHEMICAL RESEARCH 2017 679
Table 3 Pyrrole formation
R
R
R
R
CuI 5 mol%
OMe
OMe
+
EDA 10 mol%
toluene 110 °C
N
N
H
O
13
O
62%
yield
18
17
R= 4-MeOC6H4
HO
OMe
OH
Entry
R1
Cl
Me
OMe
H
NMe2
NBn2
NBn2
R2
H
H
H
OMe
H
R3
H
H
H
H
H
H
Cl
Product
10b
10c
10d
10e
10f
10g
10h
Yield (%)
70
73
70
62
64
72
70
1
2
3
4
5
6
7
OMe
BBr3 Et2O, 9 eq.
N
O
H
H
(5)
Lamellarin R
OH
Scheme 4 Attempts to obtain lamellarin R.
did not take place, and we recovered only unreacted pyrrole 16
(Scheme 3).
Our unsuccessful attempts to acylate 16 prompted us to
modify the order of the transformations. Thus, we decided to
prepare the Fürstner intermediate 18 first, using our reported
porcedure,29 and then to perform the coupling between 18 and
4-iodoanisole 13 (Scheme 4). With this modification, we were
able to obtain trimethoxy lamellarin R 17 in 62% yield. Despite
the fact that deprotection of trimethoxy lamellarin R with BBr3
has been reported,33 we were unable to reproduce the procedure
to deprotect 17 (Scheme 4). To circumvent the problem of
deprotection, benzylated pyrrole 23 was prepared in three
steps (62% yield). The yield for the carboxymethylation step
(23 to 24, Scheme 5), previously described by our group,29 was
improved from 56% to 70% by performing the reaction under
sonication for 1 h, followed by stirring the reaction mixture for
5 h at room temperature (Scheme 5).
Surprisingly, 24 did not react under the conditions used
to arylate 18 (Scheme 4). Buchwald reported32 that the best
results for this transformation are obtained when N,N′-
dimethylcyclohexan-1,2-diamine (L3) and N,N′-dimethyl-
ethylenediamine (L2) are used as the ligands. Indeed, when
23 was subjected to Buchwald’s conditions using these ligands,
25 was readily obtained in 96% (N,N′-dimethylcyclohexan-
1,2-diamine) and 64% (N,N′-dimethylethylenediamine)
yields (Scheme 5). Finally, removal of the benzyl protective
groups was conducted with H2/Pd(OH)2 in methanol to afford
lamellarin R (5) in quantitative yield. All of the intermediates
and products were satisfactorily characterised, and the 1H NMR
chemical shifts for compound 5 compared favourably with
Scheme
3
N-arylation of 3,4-diaryl-substituted pyrroles under
Buchwald’s conditions.
used instead of Buchwald’s N,N’-dimethylethylenediamine.
After 18 h of reaction, we were delighted to isolate the
desired 1,3,4-triarylpyrrole 14 in 80% yield. When 3,4-bis(4-
methoxyophenyl)pyrrole 1529 was coupled to 4-iodoanisole
13 under the above conditions, 1,3,4-triarylpyrrole 16 was
isolated in 86% yield in a reproducible manner. Jia was able
to introduce the carboxymethyl functionality into the pyrrole
moiety using a Vilsmeier–Haack formylation, oxidation and
esterification sequence of reactions33. Since we were able to
introduce the same functionality into a 3,4-diaryl-substituted
pyrrole with trichloroacetyl chloride in the presence of
4-dimethylaminopyridine (DMAP), followed by methanolysis,29
compound 16 was subjected to our conditions to obtain the
desired trimethoxy lamellarin R 17. Unfortunately, this reaction
those reported in the literature25,33
.
Originally, 1H and 13C NMR spectra for lamellarin R
1
prepared by us were recorded in CDCl3; H NMR (CDCl3,
300 MHz): δ 7.14 (d, J = 8.7 Hz, 2H), 7.05 (d, J = 8.6 Hz,
2H), 6.92 (s, 1H), 6.90 (d, J = 8.7 Hz, 2H), 6.82 (d, J = 8.7 Hz,
2H), 6.71 (d, J = 8.6 Hz, 2H), 6.60 (d, J = 8.7 Hz, 2H), 3.40
(s, 3H)]. Some differences in chemical shifts were observed
between the spectra in CDCl3 and those collected in deuterated
acetone reported by Iwao.25 When we recorded the spectra in
deuterated acetone, our 13C NMR spectrum was identical to
1
Iwao’s spectrum. However, our H NMR spectrum showed
some minor differences in the chemical shifts for the OH

680 JOURNAL OF CHEMICAL RESEARCH 2017
Scheme 5 Synthesis of lamellarin R.
Experimental
signals compared to Iwao’s spectrum, which we attributed to
differences in concentration.
Commercial reagents were purchased from Sigma-Aldrich and were
used without further purification. Solvents were purified by distillation
and were dried using Na/benzophenone when required. All reactions
were monitored by TLC. Crude-mixture purifications were performed
by flash column chromatography (FCC) on silica gel 60 mesh. NMR
measurements were performed on a Varian Inova 300 MHz instrument
using Me4Si as internal standard. Infrared (IR) spectra were recorded
on a PerkinElmer IR-FT with ATR Spectrum 400 spectrophotometer.
High-resolution mass spectra (HRMS) were collected using a JEOL
SMX-102a spectrometer. Melting points were obtained on a MeltTemp
apparatus and are uncorrected.
To the best of our knowledge, two routes have been reported for
the synthesis of lamellarin R. The first, in 2008, by Iwao25 relies
on Pd-mediated coupling reactions between 3,4-dibromopyrrole
and the corresponding aryl derivative to obtain lamellarin R in
8% yield over eight steps. In 2011, Jia33 reported a biomimetic
approach for lamellarin R (five steps, 53% overall yield) consisting
of oxidative transformations. The introduction of the carboxyl
functionality was achieved via a sequence of Vilsmeier–Haack
formylation, oxidation and esterification reactions. However,
2-(4-methoxyphenyl)acetaldehyde is not readily available, and
some additional steps are required for its preparation, which has a
detrimental effect on the overall yield.
Synthesis of 2,3-diarylacrylonitrile derivatives; general procedure
2-(4-Chlorophenyl)-3-phenylacrylonitrile (8b)
A 30% solution of NaOMe in MeOH (2.86 mL, 16 mmol) was added
to a mixture of 4-chlorophenylacetonitrile (2.00 g, 13.27 mmol)
and benzaldehyde (1.41 g, 13.27 mmol) in MeOH (90 mL), at room
temperature under nitrogen. The mixture was refluxed for 12 h. The
reaction mixture was cooled to room temperature, diluted with 50%
EtOAc–hexanes (100 mL), washed successively with H2O (3 × 30 mL)
and brine (30 mL), dried over Na2SO4 and the solvent removed in
vacuo to afford 3.00 g (95% yield) of the desired product (used without
further purification in the next reaction): White solid; m.p. 89–91 °C;
Conclusions
A simple procedure for the preparation of non-symmetrical
3,4-diarylpyrrolesinexcellentyieldsemployingreadilyavailable
starting materials has been developed. Our method is amenable
to scaling and starts from easily prepared succinonitriles as
1,4-dicarbonyl surrogates. Using our protocol, we were able to
synthesise lamellarin R (5) in 42% overall yield. We believe
that this methodology might be of practical use for synthetic
chemists and can be implemented with suitable modifications
for the preparation of other 3,4-diarylpyrrole structural motifs
commonly present in the lamellarin family of alkaloids.
1
IR (νmax/cm−1): 3057, 2217, 1598, 1492, 821, 750; H NMR (CDCl3,
300 MHz): δ 7.92–7.85 (m, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.51 (s, 1H),
7.49–7.44 (m, 3H), 7.41 (d, J = 8.6 Hz, 2H); 13C NMR (CDCl3, 75 MHz):
δ 147.9, 142.6, 135.3, 133.5, 133.0 130.8, 129.4, 129.1, 127.3, 117.7,

JOURNAL OF CHEMICAL RESEARCH 2017 681
110.5; MS m/z (relative intensity): 204 (100%), 239 (60%), 240 (11%)
(M+), 241 (19%).
2-(4-chlorophenyl)-3-phenylacrylonitrile 8b (2.9 g, 12.1 mmol) in
DMF (81 mL) at room temperature. After the addition was completed,
the resultant mixture was heated at 100 °C (oil bath) for 6 h. The
reaction mixture was then poured into ice-water (ca. 150 mL) to
precipitate the product. The solid was filtered and rinsed with
H2O (100 mL). The product was then dried in vacuo to afford the
desired succinonitrile: Yellow-cream solid (2.77 g, 86% yield), m.p.
172–173 °C; IR (νmax/cm−1): 2941, 2247, 1492, 1097, 702; 1H NMR
(DMSO-d6, 300 MHz): δ 7.52 (d, J = 8.5 Hz, 2H), 7.50–7.41 (m, 5H),
7.39 (d, J = 8.5 Hz, 2H), 5.25–5.15 (m, J = 8.3, 4.3 Hz, 2H); 13C NMR
(DMSO-d6, 75 MHz): δ 134.4, 134.3, 132.4, 132.4, 131.6, 131.6, 130.9,
130.6, 129.6, 129.5, 128.9, 128.6; MS m/z (relative intensity): 116
(72%), 150 (100%), 204 (28%), 266 (7%) (M+), 267 (1%), 268 (2%).
2-Phenyl-3-(p-tolyl)succinonitrile (9c) C17H14N2, from 3-phenyl-
2-(p-tolyl)acrylonitrile 8c (2 g, 9.1 mmol) gave 2.00 g (89% yield):
Pale yellow powder; m.p. 166–171 °C; IR (νmax/cm−1): 3059, 2941,
3-Phenyl-2-(p-tolyl)acrylonitrile (8c) C16H13N, from 4-methyl-
phenylacetonitrile (3.00 g, 22.9 mmol) and benzaldehyde (2.43
g, 22.9 mmol) gave 4.76 g (95% yield): Pale yellow powder; m.p.
38–39 °C; IR (νmax/cm−1): 3054, 3030, 2216, 1605, 1445, 909, 689;
1H NMR (CDCl3, 300 MHz): δ 7.93–7.87 (m, 2H), 7.59 (d, J = 8.2 Hz,
2H), 7.51 (s, 1H), 7.49–7.41 (m, 3H), 7.26 (d, J = 7.9 Hz, 2H), 2.41 (s,
3H); 13CNMR (CDCl3, 75 MHz): δ 141.1, 139.3, 133.8, 131.6, 130.3,
129.7, 129.1, 128.8, 125.8, 118.1, 111.5, 21.2; MS m/z: 219 (M+).
2-(4-Methoxyphenyl)-3-phenylacrylonitrile (8d) C16H13NO, from
4-methoxyphenylacetonitrile (2.00 g, 13.6 mmol) and benzaldehyde
(1.44 g, 13.6 mmol) gave 2.80 g (87% yield): Pale yellow solid; m.p.
71–74 °C; IR (νmax/cm−1): 2964, 2843, 2208, 1510, 1253, 1179, 692;
1H NMR (CDCl3, 300 MHz): δ 7.89–7.81 (m, 2H), 7.60 (d, J = 8.8 Hz,
2H), 7.45 (s, 1H), 7.48–7.35 (m, 3H), 6.95 (d, J = 8.9 Hz, 2H), 3.84 (s,
3H); 13C NMR (CDCl3, 75 MHz): δ 161.4, 141.8, 134.8, 131.1, 128.9,
128.7, 126.4, 125.7, 118.5, 114.3, 108.6, 55.4; MS m/z: 235 (M+).
2-(2-Methoxyphenyl)-3-phenylacrylonitrile (8e) C16H13NO, from
2-methoxyphenylacetonitrile (1.00 g, 7.35 mmol) and benzaldehyde
(861 mg, 7.35 mmol) gave 1.69 g (98% yield): Amber oil; IR (νmax/cm−1):
1
2246, 1494, 1454, 1025, 751, 698; H NMR (acetone-d6 300 MHz,): δ
7.53–7.38 (m, 5H), 7.33–7.22 (m, 4H), 5.01–4.80 (m, 2H), 2.37 (s, 3H);
13C NMR (DMSO-d6, 75 MHz): δ 139.1, 139.0, 132.8, 132.7, 132.7,
130.0, 129.8, 129.6, 129.6, 129.5, 129.5, 129.0, 128.9, 128.7, 128.6,
119.2, 119.1, 119.1, 118.9, 105.1, 41.8, 21.3. MS m/z: 246 (M+).
1
2-(4-Methoxyphenyl)-3-phenylsuccinonitrile (9d) C17H14N2O, from
2-(4-methoxyphenyl)-3-phenylacrylonitrile 8d (2.5 g, 10.6 mmol) gave
2.53 g (89% yield): Yellow powder; m.p. 152–154 °C; IR (νmax/cm−1):
2938, 2246, 1516, 1250, 1029, 747; 1H NMR (DMSO-d6, 300 MHz): δ
7.46–7.36 (m, 5H), 7.34 (d, J = 8.6 Hz, 1H), 7.28 (d, J = 8.6 Hz, 1H),
6.97 (d, J = 7.2 Hz, 2H), 5.15–4.91 (m, 2H), 3.75 (s, 3H); 13C NMR
(DMSO-d6, 75 MHz): δ 159.6, 159.5, 132.3, 132.2, 129.7, 129.5, 128.9,
128.5, 128.2, 124.0, 118.7, 118.6, 118.5, 114.3, 55.2. MS m/z: 262 (M+).
2-(2-Methoxyphenyl)-3-phenylsuccinonitrile (9e) C17H14N2O, from
2-(2-methoxyphenyl)-3-phenylacrylonitrile 8e (3.9g, 16.6 mmol) gave
3.43g (79% yield): Light yellow oil; IR (νmax/cm−1): 2946, 2244, 1597,
1492, 1245, 1020, 697; 1H NMR (CDCl3,300 MHz): δ 7.60 (d, J = 7.4 Hz,
2H), 7.48 (t, J = 8.3 Hz, 1H), 7.49–7.38 (m, 5H), 7.06 (t, J = 7.5 Hz, 1H),
6.97 (d, J = 8.3 Hz, 1H), 4.62 (d, J = 4.6 Hz, 1H), 4.43 (d, J = 4.7 Hz, 1H),
3.93 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ 156.1, 155.7, 132.3, 131.0,
129.7, 129.4, 129.3, 129.2, 128.9, 128.5, 127.7, 121.4, 121.0, 119.9, 117.1,
117.0, 110.9, 55.9, 55.7, 41.5, 40.1, 39.3, 37.9. MS m/z: 262 (M+).
2-[4-(Dimethylamino)phenyl]-3-phenylsuccinonitrile (9f) C18H17N3;
from 2-(4-(dimethylamino)phenyl)-3-phenylacrylonitrile 8f (2.35g,
9.5 mmol) gave 2.46 g (94% yield): Brick-red powder; m.p. 145–147 °C;
IR (νmax/cm−1): 2923, 2249, 1618, 1528, 1367, 697; 1H NMR (DMSO-d6,
300 MHz): δ 7.50–7.39 (m, 5H), 7.25 (d, J = 8.8 Hz, 1H), 7.20 (d,
J = 8.7 Hz, 1H), 6.74 (d, J = 8.9 Hz, 2H), 6.73 (d, J = 8.9 Hz, 2H), 5.05 (t,
1H), 4.96 (t, 1H), 2.94 (s, 6H);13C NMR (DMSO-d6, 75 MHz): δ 150.9,
150.9, 133.1, 132.9, 129.6, 129.4, 129.3, 129.0, 128.7, 119.5, 119.3, 119.2,
119.2, 119.1, 112.6, 112.5, 112.1, 40.4, 40.3, MS m/z: 275 (M+).
2838, 2212, 1596, 1245, 748; H NMR (CDCl3, 300 MHz): δ 8.15 (dd,
J = 7.6, 1.4 Hz, 1H), 7.97 (s, 1H), 7.75–7.66 (m, 2H), 7.49–7.34 (m, 5H),
7.07 (t, J = 7.3 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 3.89 (s, 3H); 13C NMR
(CDCl3, 75 MHz): δ 131.9, 128.9, 129.0, 128.57, 126.1, 124.2, 123.1,
123.1, 120.8, 119.4, 119.4, 110.7, 110.7, 55.64; MS m/z: 235 (M+).
2-(4-(Dimethylamino)phenyl)-3-phenylacrylonitrile (8f) C17H16N2,
from 4-(dimethylamino)phenylacetonitrile (5.46g, 34.1 mmol) and
benzaldehyde (3.60 g, 34.1 mmol) gave 7.12 g (84% yield): Bright yellow
solid; m.p. 103–104 °C; IR (νmax/cm−1): 3031, 2900, 2198, 1525, 1371,
1172; 1H NMR (CDCl3, 300 MHz): δ 7.86 (d, J = 8.7 Hz, 2H), 7.69–7.59
(m, 2H), 7.41 (s, 1H), 7.45–7.28 (m, 3H), 6.73 (d, J = 9.1 Hz, 2H), 3.06
(s, 6H); 13C NMR (CDCl3, 75 MHz): δ 142.6, 135.6, 131.3, 128.9, 128.0,
125.5, 121.6, 119.5, 111.6, 104.6, 104.5, 40.1; MS m/z: 248 (M+).
2-[4-(Dibenzylamino)phenyl]-3-phenylacrylonitrile (8g) C29H24N2,
from 4-(N,N-dibenzylamino)phenylacetonitrile (1.00 g, 3.2 mmol)
and benzaldehyde (343 mg, 3.2 mmol) gave 1.26 g (98% yield): Bright
orange powder; m.p. 81–82 °C; IR (νmax/cm−1): 3028, 2211, 1607,
1
1519, 1241; H NMR (CDCl3, 300 MHz): δ 7.86–7.78 (m, 2H), 7.49
(d, J = 9.0 Hz, 2H), 7.44–7.21 (m, 13H), 6.77 (d, J = 9.0 Hz, 2H), 4.71
(s, 3H); 13C NMR (CDCl3,75 MHz): δ 149.7, 137.8, 137.7, 137.6, 134.4,
129.7, 128.9, 128.9, 127.2, 127.2, 126.5, 122.7, 118.3, 112.5, 111.6, 54.3;
MS m/z 400 (M+).
3-(4-Chlorophenyl)-2-[4-(dibenzylamino)phenyl]acrylonitrile
(8h) C29H23N2Cl, from 4-(N,N-dibenzylamino)phenylacetonitrile (2 g,
4.6 mmol) and 4-chlorobenzaldehyde (646 mg, 4.6 mmol) gave 2.01 g
(95% yield): Orange-brownish powder; m.p. 97–99 °C; IR (νmax/cm−1):
3058, 3027, 2212, 1519, 1200, 729; 1H NMR (CDCl3, 300 MHz): δ 7.73
(d, J = 8.6 Hz, 2H), 7.46 (d, J = 9.0 Hz, 2H), 7.38 (s, 1H), 7.37–7.19
(m, 12H), 6.75 (d, J = 9.0 Hz, 2H), 4.70 (s, 4H); 13C NMR (CDCl3,
75 MHz): δ 149.9, 137.7, 135.9, 135.4, 132.9, 130.1, 129.1, 128.9,
127.2, 126.5, 122.4, 118.1, 112.5, 112.2, 105.0, 54.3; MS m/z (relative
intensity): 91 (100%), 203 (18%), 343 (23%), 434 (46%), 435 (14%)
(M+), 436 (15%).
2,3-Bis[4-(benzyloxy)phenyl]acrylonitrile (20) C29H23NO2, from
4-(benzyloxy)phenylacetonitrile (500 mg, 2.24 mmol) and 4-(benzyloxy)
benzaldehyde (475 mg, 2.24 mmol) gave 890 mg (95% yield): Yellow
solid; m.p.130–131 °C; IR (νmax/cm−1): 3063, 3032, 2216, 1248; 1H NMR
(CDCl3, 300 MHz): δ 7.84 (d, J = 9 Hz, 2H), 7.57 (d, J = 9 Hz, 2H),
7.45–7.33 (m, 11 H), 7.02 (d, J = 9 Hz, 2H), 7.00 (d, J = 9 Hz, 2H), 5.11 (s,
2H), 5.09 (s, 2H); 13C NMR (CDCl3, 75 MHz): δ 160.2, 159.2, 157.7, 139.9,
136.5, 136.3, 130.9, 128.6, 128.2, 128.1, 127.5, 127.4, 127.0, 126.9, 118.6,
115.3, 115.3, 115.1, 108.4, 70.1, 70.0. MS: m/z: 417 (M+).
2-[4-(Dibenzylamino)phenyl]-3-phenylsuccinonitrile (9g) C30H25N3,
from 2-(4-(dibenzylamino)phenyl)-3-phenylacrylonitrile 8g (2.00 g,
5 mmol) gave 1.92 g (90% yield): Orange powder; m.p. 115–117 °C; IR
(νmax/cm−1): 2863, 2244, 1613, 1520, 721; 1H NMR (CDCl3,300 MHz): δ
7.81 (d, J = 7.6 Hz, 2H), 7.49 (d, J = 8.1 Hz, 2H), 7.45–7.19 (m, 13H), 6.77
(d, J = 8.5 Hz, 2H), 4.84–4.62 (m, 6H); 13C NMR (CDCl3, 75 MHz): δ
149.8, 137.8, 131.3, 129.4, 129.3, 129.1, 128.9, 128.8, 128.4, 128.2, 127.1,
127.0, 126.5, 118.2, 117.6, 117.6, 112.8, 112.6, 54.2, 43.7, 42.7. MS m/z:
427 (M+).
2-(4-Chlorophenyl)-3-[4-(dibenzylamino)phenyl]succinonitrile
(9h) C30H24N3Cl, from 3-(4-chlorophenyl)-2-(4-(dibenzylamino)
phenyl)acrylonitrile 8h (1 g, 2.3 mmol) gave 980 mg (92% yield):
Orange powder; m.p. 137–140 °C; IR (νmax/cm−1): 3029, 2244, 2195,
1
1612, 1520, 1355, 729; H NMR (CDCl3, 300 MHz): δ 7.39–7.18 (m,
12H), 7.15 (d, J = 8.5 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.69 (d, J = 8.9
Hz, 2H), 4.67 (s, 4H), 4.12 (s, 2H); 13C NMR (CDCl3, 75 MHz): δ 149.9,
137.8, 135.7, 129.8, 129.7, 129.4, 129.3, 128.8, 127.2, 126.6, 117.7, 117.4,
117.3, 112.7, 54.3, 43.1, 42.6; MS m/z (relative intensity): 91 (100%),
149 (66%), 311 (58%), 434 (16%), 461 (3%)(M+), 462 (1%), 463 (1%).
Synthesis of 2,3-diarylsucciononitrile derivatives; general procedure
2-(4-Chlorophenyl)-3-phenylsuccinonitrile (9b) C16H11ClN2
A solution of KCN (2.00 g, 30.7 mmol) and NH4Cl (1.00 g,
18.8 mmol) in H2O (27 mL) was added dropwise to a solution of
2,3-Bis[4-(benzyloxy)phenyl]succinonitrile
from 2,3-bis[4-(benzyloxy)phenyl]acrylonitrile 20 (1.8 g, 4.3 mmol)
(21)
C30H24N2O2,

682 JOURNAL OF CHEMICAL RESEARCH 2017
gave 1.80 g (95% yield): Yellow-brownish powder; m.p. 240–244 °C;
2H), 6.89–6.84 (m, 1H), 6.82–6.79 (m, 1H), 6.65 (d, J = 8.8 Hz, 2H),
4.62 (s, 4H); 13C NMR (CDCl3, 75 MHz): δ 147.6, 138.9, 136.2, 129.3,
128.6, 128.6, 128.1, 126.9, 126.9, 125.6, 124.4, 123.5, 123.3, 117.2,
116.7, 112.6, 54.3; HRMS (EI) m/z: (M+) calcd for C30H26N2: 414.2096;
found: 414.2087.
N,N-Dibenzyl-4-[4-(4-chlorophenyl)-1H-pyrrol-3-yl]aniline (10h)
C30H25ClN2, from 2-(4-chlorophenyl)-3-[4-(dibenzylamino)phenyl]
succinonitrile 9h (690 mg, 1.5 mmol) gave 471 mg (70% yield): Yellow
solid; m.p. 145–147 °C; IR (νmax/cm−1): 3426, 3025, 1614, 1506, 1354,
735, 551; 1H NMR (CDCl3, 300 MHz): δ 8.19 (s, br, 1H), 7.36–7.29 (m,
6H), 7.28–7.23 (m, 6H), 7.22–7.19 (m, 2H), 7.05 (d, J = 9.0 Hz, 2H),
6.86–6.82 (m, 1H), 6.81–6.78 (m, 1H), 6.66 (d, J = 8.8 Hz, 1H), 4.63
(s, 4H); 13C NMR (CDCl3, 75 MHz): δ 147.7, 138.8, 134.7, 131.2, 129.7,
129.4, 128.6, 128.3, 126.9, 126.8, 123.9, 123.5, 122.2, 117.1, 116.8,
112.6, 54.3; MS m/z (relative intensity): 217 (27%), 357 (100%), 448
(96%), 449 (28%) (M+), 450 (32%); HRMS (EI) m/z: (M+) calcd for
C30H25ClN2: 449.1784; found: 449.1774.
3,4-Bis[4-(benzyloxy)phenyl]-1H-pyrrole (23) C30H25NO2, from
2,3-bis[4-(benzyloxy)phenyl]succinonitrile 21 (1.8 g, 4 mmol) gave
1.21 g (70% yield): Yellow solid; m.p. 120–140 °C; IR (νmax/cm−1):
3443, 3061, 3030, 2883, 2852, 2549, 1696, 1593, 1497, 1247; 1H NMR
(CDCl3, 300 MHz): δ 8.19 (br s, 1H), 7.45–7.31 (m, 10H), 7.19 (d,
J = 9 Hz, 4H), 6.88 (d, J = 9 Hz, 4H), 6.81 (d, J = 3 Hz, 2H), 5.03 (s,
4H); 13C NMR (CDCl3, 75 MHz): δ 157.1, 137.2, 129.6, 128.6, 128.5,
127.9, 127.6, 123.0, 116.8, 114.5, 69.9; MS: m/z = 431 (M+).
1
IR (νmax/cm−1): 3070, 3032, 2936, 2880, 2244, 1514, 1247; H NMR
(CDCl3, 300 MHz): δ 7.42–7.35 (m, 10H), 7.13 (d, J =8.7 Hz, 4H),
6.96 (d, J = 8.7 Hz, 4H), 5.07 (s, 4H), 4.16 (s, 2H); 13C NMR (CDCl3,
75 MHz): δ 152.0, 136.4, 129.7, 128.7, 128.2, 127.5, 122.9, 117.5, 115.4,
70.1; MS: m/z = 444 (M+).
Synthesis of 3,4-diraylpyrroles; typical procedure
3-(4-Chlorophenyl)-4-phenyl-1H-pyrrole (10b) C16H12ClN
A 1.0 M solution of DIBAL-H in toluene (9.5 mL, 9.5 mmol) was added
dropwise to a suspension of 2-(4-chlorophenyl)-3-phenylsuccinonitrile
9b (1.00 g, 3.8 mmol) in anhydrous toluene (25 mL) at room
temperature under nitrogen. After the addition was completed, the
mixture was stirred at room temperature for 6 h and then quenched
with aqueous 1.5 M NaH2PO4 (80 mL). The resulting heterogeneous
mixture was stirred at 100 °C for an additional period of 1 h, cooled
to room temperature, diluted with 50% EtOAc–hexanes (150 mL)
and filtered through Celite®. The two layers were separated and the
organic phase was washed with H2O (2 × 30 mL), brine (30 mL), and
then dried (Na2SO4). After removal of the solvent in vacuo, the residue
was fractionated by FCC (SiO2, 30% EtOAc–hexanes) to obtain
the product (672 mg, 70% yield): Brown solid; m.p. 73–75 °C; IR
(νmax/cm−1): 3422, 1671, 1532, 1487, 1090, 698, 518; 1H NMR (CDCl3,
300 MHz): δ 8.22 (br s, 1H), 7.44–7.12 (m, 9H), 6.94–6.78 (m, 2H);
13C NMR (CDCl3, 75 MHz): δ 135.5, 134.3, 131.5, 129.8, 128.6, 128.4,
128.4, 126.0, 123.6, 122.5, 117.7, 117.5; MS m/z (relative intensity): 217
(50%), 253 (100%), 254 (22%) (M+), 255 (31%); HRMS (EI) m/z: (M+)
calcd for C16H12ClN: 253.0658; found: 253.0663.
Methyl-3,4-bis(4-benzyloxyphenyl)-1H-pyrrole-2-carboxylate (24)
C32H27NO4
3-Phenyl-4-(p-tolyl)-1H-pyrrole (10c) C17H15N, from 2-(4-methyl-
phenyl)-3-phenylbutanedinitrile 9c (500 mg, 2.03 mmol) gave 346 mg
(73% yield): Brown solid; m.p. 51–52 °C; IR (νmax/cm−1): 3416, 3024,
A solution of trichloroacetyl chloride (230 μL, 2.06 mmol) in anhydrous
THF (2 mL) was added dropwise to a mixture of pyrrole 23 (587,
1.36 mmol) and DMAP (268 mg, 2.2 mmol) in anhydrous THF (2 mL) at
0 °C. After the addition was completed, the resultant mixture was stirred at
room temperature for 4 h. The mixture was then transfer to an ultrasound
bath and sonicated for three periods of 45 min each. The reaction was
quenched by the addition of 30% NaOMe in MeOH (1 mL, 5.5 mmol)
and MeOH (7 mL) and the sonication was continued for 30 minutes. The
mixture was diluted with 50% EtOAc–hexanes (50 mL) and washed
successively with H2O (3 × 20 mL) and brine (20 mL), dried over Na2SO4
and the solvent evaporated in vacuo. The residue was fractionated by FCC
(SiO2, 30% EtOAc–hexanes) to afford 466 mg (70% yield) of the desired
product: Pale yellow solid; m.p.166–168 °C; IR (νmax/cm−1): 3307, 3000,
1
2918, 1712, 1535, 1439, 1082, 770, 697; H NMR (CDCl3, 300 MHz):
δ 8.29 (s, 1H), 7.38–7.25 (m, 5H), 7.22 (d, J = 8.1 Hz, 2H), 7.12 (d,
J = 8.4 Hz, 2H), 6.95–6.91 (m, 2H), 3.42 (s, 3H);13C NMR (CDCl3,
75 MHz): δ 136.0, 135.3, 132.9, 129.9, 129.0, 128.6, 128.5, 128.2, 125.7,
123.5, 117.5, 117.4, 21.2; HRMS (EI) m/z: (M+) calcd for C17H15N:
233.1204; found: 233.1205.
3-(4-Methoxyphenyl)-4-phenyl-1H-pyrrole (10d) C17H15NO, from
2-(4-methoxyphenyl)-3-phenylsuccinonitrile 9d (524 mg, 2 mmol) gave
349 mg (70% yield): Yellow solid; m.p.100–102 °C; IR (νmax/cm−1): 3418,
1499, 1240, 1174, 1025, 698; 1H NMR (CDCl3, 300 MHz): δ 8.29 (br s,
1H), 7.37–7.27 (m, 4H), 7.29–7.20 (m, 3H), 6.94 (s, 1H), 6.91–6.83 (m,
3H), 3.84 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ 157.8, 130.0, 129.6,
128.4, 127.9, 123.19, 118.2, 116.8, 116.8, 113.6, 55.2; MS: m/z: 249
(M+); HRMS (ESI) m/z: (M+H) calcd for C17H15NO: 250.1231; found:
250.1233.
1
2947, 2832, 1674, 1246; H NMR (CDCl3, 300 MHz): δ 9.24 (br s, 1H),
7.16 (d, J = 9 Hz, 2H), 7.00–7.03 (m, 3H), 6.81 (d, J = 9 Hz, 2H), 6.72 (d,
J = 9 Hz, 2H), 3.79 (s, 3H), 3.73 (s, 3H), 3.69 (s, 3H); 13C NMR (CDCl3,
75 MHz): δ 161.5, 158.5, 158.0, 131.8, 129.5, 127.1, 126.5, 120.0, 119.4,
113.7, 113.1, 55.2, 55.1, 51.2; MS: m/z = 489 (M+).
3-(2-Methoxyphenyl)-4-phenyl-1H-pyrrole (10e) C17H15NO, from
2-(2-methoxyphenyl)-3-phenylsuccinonitrile 9e (500 mg, 1.9 mmol)
gave 294 mg (62% yield): Yellow oil; IR (νmax/cm−1): 3374, 2935, 1702,
1433, 1239, 1022, 749, 697; 1H NMR (CDCl3, 300 MHz): δ 8.29 (br s,
1H), 7.33–7.12 (m, 6H), 7.19–7.05 (m, 2H), 6.98–6.77 (m, 3H), 3.44 (s,
3H); 13C NMR (CDCl3, 75 MHz): δ 156.9, 137.0, 136.9, 131.6, 128.0,
127.6, 127.4, 125.3, 120.5, 118.7, 116.5, 111.1, 55.1; HRMS (EI) m/z:
(M+) calcd for C17H15NO: 249.1154; found: 249.1157.
N-Arylation of 3,4-diraylpyrroles; general procedure
1-(4-Methoxyphenyl)-3,4-diphenyl-1H-pyrrole (14) C23H19NO
CuI (5 mg, 5 mol%), 3,4-diphenyl-1H-pyrrole 12 (100 mg, 0.46 mmol)
and anhydrous K3PO4 (212 mg, 0.96 mmol) were added to a Schlenck
flask. The reaction vessel was evacuated and back-filled with nitrogen.
This sequence was repeated two more times. 1-(Methoxy)-4-
iodobenzene (130 mg, 0.55 mmol), ethylenediamine (5 mg, 90 μmol)
and toluene (1 mL) were then added simultaneously under a stream of
nitrogen. The reaction vessel was sealed and stirred in a pre-heated oil
bath at 120 °C for 18 h. The reaction mixture was allowed to cool to room
temperature and diluted with ethyl acetate, filtered through Celite®, and
the filter rinsed with ethyl acetate. The solvent was evaporated in vacuo
and the residue was fractionated by FCC (SiO2, 20% EtOAc–hexanes)
to afford 119 mg (80% yield) of the desired product: White-yellow
solid; m.p. 82–84 °C; IR (νmax/cm−1): 3056, 1602, 1516, 1247, 1027,
695; 1H NMR (CDCl3, 300 MHz): δ 7.37 (d, J = 8.9 Hz, 2H), 7.34–7.30
(m, 4H), 7.30–7.25 (m, 4H), 7.25–7.19 (m, 2H), 7.10 (s, 2H), 6.96 (d,
J = 8.9 Hz, 2H), 3.822 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ 157.9,
135.5, 133.9, 128.5, 128.3, 125.9, 125.1, 121.9, 119.0, 114.8, 55.6.
N,N-Dimethyl-4-(4-phenyl-1H-pyrrol-3-yl)aniline (10f) C18H18N2,
from
2-[4-(dimethylamino)phenyl]-3-phenylsuccinonitrile
9f
(600 mg, 2.18 mmol) gave 366 mg (64% yield): Brown-red solid; m.p.
25–27 °C; IR (νmax/cm−1): 3404, 2882, 1614, 1534, 1505, 1057, 770, 550;
1H NMR (CDCl3,300 MHz): δ 8.23 (s, br, 1H), 7.38–7.22 (m, 5H), 7.16
(d, J = 8.9 Hz, 3H), 6.82 (s, 1H), 6.82 (s, 1H), 6.67 (d, J = 8.9 Hz, 2H),
2.93 (s, 6H);13C NMR (CDCl3, 75 MHz): δ 148.9, 136.2, 129.4, 128.5,
128.1, 125.5, 124.2, 123.3, 120.6, 117.2, 116.7, 112.7, 40.8; HRMS (EI)
m/z: (M+) calcd for C18H18N2: 262.1470; found: 262.1464.
N,N-Dibenzyl-4-(4-phenyl-1H-pyrrol-3-yl)aniline (10g) C30H26N2,
from 2-[4-(dibenzylamino)phenyl]-3-phenylsuccinonitrile 9g (1.09 g,
2.55 mmol) gave 762 mg (72% yield): Yellow solid; m.p.116–118 °C; IR
(νmax/cm−1): 3426, 3027, 1507, 1356, 1238, 730, 694; 1H NMR (CDCl3,
300 MHz): δ 8.19 (s, br, 1H), 7.39–7.23 (m, 5H), 7.08 (d, J = 8.8 Hz,
1,3,4-Tris(4-methoxyphenyl)-1H-pyrrole (16) C25H23NO3, from
3,4-bis(4-methoxyphenyl)-1H-pyrrole 15 (201 mg, 0.72 mmol) gave

JOURNAL OF CHEMICAL RESEARCH 2017 683
236 mg (86% yield): White-yellow solid; m.p. 59–63 °C; IR (νmax
/
Received 3 July 2017; accepted 5 November 2017
Paper 1704864
https://doi.org/10.3184/174751917X15105690662863
Published online: 11 December 2017
cm−1): 2956, 2832, 1706, 1515, 1239, 1029, 826; 1H NMR (CDCl3,
300 MHz): δ 7.37 (d, J = 9.0 Hz, 2H), 7.23 (d, J = 8.8 Hz, 4H), 7.05 (s,
1H), 6.96 (d, J = 8.9 Hz, 2H), 6.83 (d, J = 8.9 Hz, 4H), 3.83 (s, 3H), 3.80
(s, 6H); 13C NMR (CDCl3, 75 MHz): δ 158.0, 157.7, 134.1, 129.6, 128.1,
124.7, 121.7, 118.3, 114.8, 113.7, 55.6, 55.2; HRMS (EI) m/z: (M+) calcd
for C25H23NO3: 358.1678; found: 385.1684.
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2
3
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Methyl-1,3,4-tris[4-(methoxy)phenyl]-1H-pyrrole-2-carboxylate
(Trimethoxy lamellarin R) (17) C27H25NO5, from 3,4-bis(4-
methoxyphenyl)-1H-pyrrole-2-carboxylate 18 (30 mg, 90 μmol)
gave 25 mg (62% yield): Yellow solid; m.p. 42–44 °C; IR (νmax/cm−1):
2949, 1702, 1512, 1240, 832; 1H NMR (CDCl3, 300 MHz): δ 7.31
(d, J = 9.0 Hz, 2H), 7.20 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 8.9 Hz, 2H),
7.00 (s, 1H), 6.96 (d, J = 9.0 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 6.75 (d,
J = 8.9 Hz, 2H), 3.86 (s, 3H), 3.83 (s, 3H), 3.76 (s, 3H), 3.47 (s, 3H);
13C NMR (CDCl3, 75 MHz): δ 168.3, 161.7, 158.9, 158.4, 158.0, 134.0,
131.8, 131.0, 129.4, 127.3, 127.1, 126.8, 126.5, 124.9, 113.8, 113.6, 113.0,
55.5, 55.2, 55.2, 50.9; HRMS (EI) m/z; (M+) calcd for C27H25NO5:
443.1733; found: 443.1731.
4
5
6
7
8
9
N. Lindquist, W. Fenical, G.D. van Duyne and J. Clardy, J. Org. Chem.,
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Methyl-1,3,4-tris[4-(benzyloxy)phenyl]-1H-pyrrole-2-carboxylate
(Tribenzyloxy lamellarin R) (25) C45H37NO5, from methyl-3,4-bis(4-
benzyloxyphenyl)-1H-pyrrole-2-carboxylate 24 (95 mg, 0.19 mmol)
A.R. Carroll, B.F. Bowden and J.C. Coll, Aust. J. Chem., 1993, 46, 489.
10 S. Urban, M.S. Butler and R.J. Capon, Aust. J. Chem., 1994, 47, 1919.
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gave 125 mg (96% yield) as a white solid; m.p. 69–72 °C; IR (νmax
/
cm−1): 3031, 1702, 1510, 1220, 1010, 832, 695; 1H NMR (CDCl3,
300 MHz): δ 7.41–7.23 (m, 15H), 7.21 (d, J = 9.0 Hz, 2H), 7.13 (d,
J = 8.8 Hz, 2H), 6.94 (dd, J = 8.9, 1.5 Hz, 4H), 6.90 (s, 1H), 6.85 (d,
J = 8.8 Hz, 2H), 6.73 (d, J = 8.9 Hz, 2H), 5.00 (s, 2H), 4.97 (s, 2H),
4.90 (s, 2H), 3.37 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ 161.7, 158.2,
157.8, 157.3, 137.1, 137.1, 136.7, 134.2, 131.9, 131.0, 129.4, 128.7, 128.6,
128.2, 128.0, 128.0, 127.7, 127.7, 127.6, 127.1, 127.1, 126.6, 125.0, 121.3,
114.8, 114.6, 114.1, 70.3, 70.0, 51.0; HRMS (ESI) m/z: (M+H) calcd for
C45H37NO5: 672.2750; found: 672.2726.
14 S. Khiati, J. Seol, K. Agama, I. Dalla-Rosa, S. Agrawal, K. Fesen, H.
Zhang, K.C. Neuman and Y. Pommier, Mol Pharmacol., 2014, 86, 193.
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Methyl-1,3,4-tris(4-hydroxyphenyl)-1H-pyrrole-2-carboxylate
(Lamellarin R) (5) C24H19NO5
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through Celite®, the filter was rinsed with EtOAc, and the solvent
was evaporated under reduced pressure to afford 60 mg (quantitative
yield) of the desired product (not purified further): Yellow-brownish
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(d, J = 8.7 Hz, 2H), 3.40 (s, 3H); 13C NMR (acetone-d6, 75 MHz): δ
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Acknowledgements
We thank DGAPA-UNAM for financial support (Grant
IN212513). HZ thanks CONACYT for a scholarship (216074).
We also thank Marisela Gutierrez and Rosa I. del Villar from
USAII (F.Q. UNAM) for several spectroscopic determinations.