A protecting group-free divergent synthesis of natural benzofurans via one-pot synthesis of 2-bromo-6-hydroxybenzofurans

Article abstract of DOI:10.1039/C8OB03102A

2-Bromo-6-hydroxybenzofurans are potentially versatile intermediates for the divergent synthesis of numerous benzofuran-based natural products and their analogues. Herein we report the first one-pot strategy for the efficient synthesis of 2-bromo-6-hydrox

Full text of DOI:10.1039/C8OB03102A

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A protecting group-free divergent synthesis of natural benzofurans via one-pot
synthesis of 2-bromo-6-hydroxybenzofurans
Aneesh Sivaraman,a Dipesh S. Harmalkar,a Jiyoon Kang,a Yongseok Choi,b and Kyeong Lee*a
aCollege of Pharmacy, Dongguk University-Seoul, Goyang, 10326, Republic of Korea
E-mail: kaylee@dongguk.edu
bDepartment of Biotechnology, Korea University, Seoul, 02841, Republic of Korea.

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Abstract: 2-Bromo-6-hydroxybenzofurans are potentially versatile intermediates for the divergent
synthesis of numerous benzofuran-based natural products and their analogues. Herein we report
the first one-pot strategy for the efficient synthesis of 2-Bromo-6-hydroxybenzofurans. The
present protocol provide shorter routes for the synthesis of moracins M, N, O and P; gramniphenols
F and G; and morunigrol C using a protecting group-free approach.

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Introduction
Natural benzofurans and their analogues are privileged structures in the field of medicinal
chemistry due to their wide range of biological and pharmacological properties. Different classes
of benzofuran compounds like moracins, ribisins, stemofurans, gramniphenols and homoegonol-
related compounds exhibiting diverse biological activities have been isolated from plants, marine
sources and bacterial or fungal metabolites etc.1a–c Among the variety of powerful methodologies
that have been well established for the construction of benzofuran scaffolds, a number of them
requires additional protection-deprotection steps to avoid complications due to the phenolic group
in the coupling partner. Additionally, most of these strategies involve the convergent synthesis of
individual benzofuran skeletons.2a–p New efficient and common pooled strategies for the synthesis
of this class of compounds are highly desirable since these compounds are of keen interest in the
field of drug discovery.
Earlier, we reported the total synthesis of moracin O and P which exhibited potent in vitro
inhibitory activity against HIF-1, a key mediator to tumor hypoxia. Furthermore, the synthesis and
biological evaluation of novel moracins O and P analogues was also carried out.3a–c Continuing
our interest in the synthesis of natural benzofurans and their derivatives, we planned an approach
involving a fewer number of steps, a broad substrate scope and the non-usage of pyrophoric
reagents.
Previously, the synthesis of substituted 2-bromobenzofuran compounds from the intra molecular
cyclization of gem-dibromoalkenes has been reported which in turn, could be synthesized by the
condensation of the aldehydes with CBr4 (Ramirez olefination).4a–d Kim et al.5a and Damodar et

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al.5b reported the synthesis of natural benzofurans using Suzuki coupling as a key step via 2-
bromobenzofurans obtained from the intramolecular cyclization of protected/modified gem-
dibromoalkenes. Rao et al. utilized functional group maneuvering techniques for tuning the
stability and reactivity of gem-dibromides for the synthesis of benzofuran-based natural
products.6a,b The aforementioned methods require additional protection-deprotection techniques
and are less divergent. However, the preparation of gem-dibromoalkenes containing two phenolic
groups has seldom been reported.
We envisioned that a divergent-pooled route for benzofuran analogues could be developed using
2-bromo-6-hydroxybenzofurans, which could serve as potentially versatile intermediates due to
their high reactivity and ease of derivatization. Hence, a direct method for the synthesis of 2-
bromo-6-hydroxybenzofurans and their applications in the synthesis of benzofuran analogues is
highly needed. Herein, we report our findings on how to gain access to the desired 2-bromo-6-
hydroxybenzofurans by using modified Ramirez olefination and its subsequent selective
intramolecular cyclization in a one-pot synthesis.

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Results and discussion
The Ramirez olefination of 2,4-dihydroxybenzaldehyde (1a) was investigated to identify a
protecting group-free conditions for the synthesis of 2-bromo-6-hydroxybenzofuran/2-
bromobenzofuran-6-ol (3a). Initial attempts to prepare 4-(2,2-dibromovinyl)benzene-1,3-diols (2)
according to the standard Ramirez olefination procedure [CBr4 (6 equiv), triphenylphosphine
(PPh3; 6 equiv), triethylamine (TEA; 12 equiv), DCM, 0 °C to room temperature (rt)] were futile
owing to its poor stability.7 Although gem-dibromoalkene 2 was found to decompose on isolation,
it exhibited considerable stability in the solvated state even at elevated temperatures. Hence, a one-
pot strategy for the synthesis of 3a from 1a via gem-dibromoalkene (2) was envisaged.
We suitably modified the Ramirez olefination for the subsequent one-pot synthesis of 3a as shown
in Table 1. Since the isolated yields of 2 could not be compared for every reaction, the conversion
of aldehyde 1a was monitored by thin layer chromatography. Zn powder was used as a molecular
scavenger in place of TEA to reduce the amount of CBr4 and PPh3 required, as has been reported.8
The initial efforts focused on complete conversion of aldehyde 1a to gem-dibromoalkene 2 using
solvents like DCM, DCE, and THF failed to give the desired results. However, efficient conversion
was observed when ACN was employed. Hence, in our procedure a solution of CBr4 (4 equiv) in
ACN was added dropwise to a stirred suspension of aldehyde (1 equiv), PPh3 (4 equiv) and Zn (4
equiv) powder at rt and stirred for an additional 30 min (Table 1). Solid NH4Cl was used to cleave
the scavenger bonding at the end of the reaction contrary to previously reported procedures which
use aqueous NH4Cl or 1N HCl solution. Thus, Ramirez olefination in ACN using the

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aforementioned conditions turned out to be excellent as it could be performed at rt due to its low
exothermic nature and also served as a suitable solvent for the subsequent cyclization reaction.
With this improved synthesis of 4-(2,2-dibromovinyl)benzene-1,3-diol (2) suitable for the one-pot
synthesis of 2-bromo-6-hydroxybenzofuran (3a) in hand, various reaction conditions were
screened for the subsequent selective intramolecular cross-coupling. Although cyclization was not
observed in the presence of Cs2CO3 (3 equiv) as a base at rt (Table 1, entry 1), the promising results
were obtained when the reaction was carried out at 85 °C, yielding 3a in 25% (entry 2). This
finding encouraged us to optimize the reaction parameters to improve the yield of 3a and
accordingly, a variety of cyclization conditions were explored, the results of which are summarized
in Table 1.
The use of 5 equiv of Cs2CO3 moderately improved the reaction yields in 5 hours (entry 3). Many
different copper species including CuI (5 mol%) have been reported as effective catalysts for the
selective intramolecular coupling of gem-dibromovinylphenols to yield 2-bromobenzofurans.4a
Hence, the model reaction was screened with varying amounts of base and CuI as the catalyst
(entries 4–6). The best results were obtained using Cs2CO3 (3.5 equiv) and CuI (5 mol%) at 85 °C,
giving the desired 3a with complete selectivity in 65% yield (entry 4).
The choice of base was also important as the selected commercially available bases (K2CO3,
Na2CO3, K3PO4, and CsF) failed to improve the yields in the above reaction (entries 7–10). During
the course of further optimization, we also studied the effect of solvents in the cyclization. For this
purpose, the gem-dibromoalkene (2) solution in ACN was evaporated nearly to dryness and the

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cyclization was performed in solvents like THF and EtOH. However, no significant improvement
in product yield was observed (entries 11–13). Tetra-n-butylammonium fluoride (TBAF)
promoted metal-free cyclization was also found to be ineffective (entry 14).4b The present one-pot
synthesis greatly simplified the work-up procedure and enabled purification to be accomplished
by simple filtration of the reaction mixture through silica gel.
Table 1. The effect of a base or an additive on the intramolecular cyclization of 4-(2,2-
dibromovinyl)benzene-1,3-diol (2)a
Br
b
O
a
Br
Br
OH
HO
O
HO
OH
HO
2
1a
3a
Unstable on isolation
Entry Base (equiv)
Additive (mol%) Solvent Temp (°C) Time (h) Yield (%)
1
2
3
4
5
6
Cs2CO3 (3)
Cs2CO3 (3)
Cs2CO3 (5)
----
ACN
ACN
ACN
ACN
ACN
ACN
rt
16
16
5
NR
25
40
65
40
65
----
85
85
85
85
85
----
Cs2CO3 (3.5)
Cs2CO3 (2.5)
Cs2CO3 (3.5)
CuI (5)
CuI (5)
CuI (10)
3
3
3

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7
K2CO3 (3.5)
Na2CO3 (3.5)
K3PO4 (3.5)
CsF (3.5)
CuI (5)
ACN
ACN
ACN
ACN
THF
85
3
45
8
CuI (5)
CuI (5)
CuI (5)
CuI (5)
CuI (5)
CuI (5)
85
85
85
70
80
70
85
3
35
9
16
16
3
20
10
11
12
13
14
NR
42b
26b
44b
NR
Cs2CO3 (3.5)
Cs2CO3 (3.5)
K3PO4 (3.5)
EtOH
THF
2
3
TBAF in THF (5) ----
ACN
16
aReagents and conditions: (a) all reactions were performed with 1a (1.5 mmol), CBr4 (6.0 mmol),
PPh3 (6.0 mmol), Zn (6.0 mmol), ACN (15 ml), rt, 1 h; followed by NH4Cl (9.0 mmol), rt, 0.5 h.;
and then (b) base (2.5-5 equiv), additive (5–10 mol%) at T °C in a solvent (15 mL) under an N2
atmosphere. bReactions were performed in a new solvent after concentrating ACN to the minimum
volume.
After having established our approach for the preparation of 3a, the scope of the reaction was
evaluated under the optimized conditions. A variety of reported 2,4-dihydroxy benzaldehydes (1a–
m, Supporting Information) possessing different substituents on the benzene rings were
examined (Table 2). Electron donating substituents at C-6 resulted in improved yields (entries 2
and 3), while a slight ortho-position effect was observed in the reaction for substituents at C-3

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(entries 4 and 5). In general, the substituents at C-5 gave lower yields (entries 6–9) with the effects
being more predominant when strongly electron withdrawing –NO2 was present (entry 9). Halogen
substituents (either Cl or Br) as well as either mono-halogen or di-halogens on the benzene rings
underwent clean conversions and afforded good yields of the corresponding di- or multi-
halogenated benzofurans, which are essential building blocks for further transformation through
selective transition metal-catalyzed cross-coupling reactions with various nucleophiles (entries
10–12). Under the optimized conditions, 2,4-dihydroxyacetophenone also reacted to give 2-
bromo-3-methyl-6-hydroxybenzofuran in good yields (entry 13).
Table 2. Synthesis of substituted 2-bromo-6-hydroxybenzofurans (3a–m) through one pot strategy.
6
R
5R
O
1
2
a
Br
O
4
HO
OH
HO
3
3a-m
1a-m
Entry
1
Substrate
Product
Yield (%)
CHO
Br
Br
65
O
HO
HO
HO
OH
3a
1a
1b
CHO
OH
2
65
O
HO
3b

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O
O
CHO
3
4
69
59
Br
Br
O
O
HO
HO
OH
HO
HO
3c
3d
1c
CHO
OH
1d
1e
CHO
OH
Br
O
HO
HO
5
6
60
3e
CHO
Br
40b
O
HO
OH
HO
3f
1f
CHO
OH
Br
7
8
9
42
10
44
O
HO
HO
3g
1g
O2N
HO
CHO
OH
O2N
HO
Br
O
3h
1h
Br
CHO
OH
Br
Br
O
HO
HO
3i
1i

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Br
Br
CHO
10
11
12
56
40
45
Br
Br
Br
O
O
O
HO
OH
HO
1j
3j
Cl
CHO
OH
Cl
HO
HO
3k
1k
Cl
Cl
CHO
OH
HO
HO
Cl
3l
Cl
1l
O
Br
13
40b
O
HO
HO
OH
3m
1m
aReagents and conditions: (a) i) 1a–m (1.5 mmol), CBr4 (6.0 mmol), PPh3 (6.0 mmol), Zn (6.0
mmol), ACN (15 ml), rt, 1 h; followed by NH4Cl (9.0 mmol), rt, 0.5 h.; and then ii) Cs2CO3 (5.25
mmol), CuI (5 mol%) at 80 °C in ACN (15 mL) under an N2 atmosphere.
bReaction were performed in an ACN:DCM (4:1) mixture for efficient conversion.
After successfully establishing the protecting group-free synthesis of the 2-bromo-6-
hydroxybenzofurans, we focused on the synthesis of bioactive benzofuran compounds using this
divergent-pooled strategy. We opted for a few of the 2-arylbenzofuran-based natural products (4–
11) to illustrate the synthetic applications of the 2-bromo-6-hydroxybenzofurans (Figure 1).

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OH
OH
OH
R1
R2
R1
O
O
HO
HO
O
OH
O
Moracin M (4)
Moracin N (5)
Gramniphenol F (8): R1 = H, R2 = OH
Gramniphenol G (9): R1 = H, R2 = OMe
Murunigrol C (10): R1 = OH, R2 = H
3',5'-di-O-methyl
OH
OH
OH
HO
HO
O
O
O
O
OH
morunigrol C (11): R1 = OMe, R2 = H
(±) Moracin O (6)
(±) Moracin P (7)
Figure 1. 2-arylbenzofuran-based natural products.
A retrosynthetic analysis for these benzofurans (4–11) involves the synthesis of two major building
blocks; substituted 2-bromo-6-hydroxybenzofurans (II) and boronic ester/acid (III). The tricyclic
fused compounds (IV) could be synthesized by the subsequent cyclization reactions from II, which
could be obtained by the one-pot synthesis from the corresponding aldehydes (I) (Scheme 1).
Moracin O (6)
Moracin P (7)
Moracin M (4)
Moracin N (5)
Gramniphenol F (8)
Gramniphenol G (9)
Murunigrol C (10)
3',5'-di-O-methyl
R1
R1
O
Br
Br
O
O
II
HO
OH
HO
morunigrol C (11)
IV
I
O
B
O
R2
III
Scheme 1. The retrosynthetic approach.
Moracins M (4) and N (5) possessing anticancer activity were first isolated from the root bark of
Morus alba and dried leaves of mulberry leaves, respectively.9a–c Earlier syntheses of moracins M

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and N have been achieved using protection-deprotection techniques or under drastic reaction
conditions.6b,10a–e Boronic ester 13 required for the synthesis of these natural products was obtained
from 3,5-dihydroxybromobenzene (12) using Mayura borylation,11 as shown in Scheme 2.
Furthermore, varying reaction conditions for the Suzuki coupling to give moracin M were screened
(Table 1, Supporting Information). The best results were achieved using DMF:H2O (4:1) as the
solvent with Pd(dppf)Cl2.DCM and K3PO4 (entry 4, Table 1, Supporting Information). Using the
optimized conditions, moracins M (4) and N (5) were synthesized from 3a and 3f with overall
yields of 54% and 7.7%, respectively (Scheme 2).
OH
OH
OH
OH
OH
R
O
O
a
b
B
Br
O
HO
OH
13
12
Moracin M (4), R = H
Moracin N (5), R = Prenyl
Scheme 2. The synthesis of moracins M (4) and N (5). Reagents and conditions: (a)
bis(pinacolato)diboron, KOAc, Pd(dppf)Cl2.DCM, 1,4-dioxane, 100 °C, 2 h, 88%; (b) 3a or 3f,
K3PO4, Pd(dppf)Cl2.DCM, DMF:H2O (4:1), 70 °C, 1 h 83% (4) and 51% (5).
After completing the synthesis of moracins M and N, we then focused on the synthesis of natural
HIF-1 inhibitors moracins O (6) and P (7), which have been isolated from Morus alba. Kaur et al.
reported the first total synthesis of these from 2,4-dihydroxybenzaldehyde (1a) utilizing Corey-
Fuchs reaction and Sonogashira coupling as key transformations over 10 steps with overall yields
of 2.21% and 2.27%, respectively.3a Considering the longer synthetic route employing pyrophoric
reagents in the aforementioned method, we designed a shorter route using prenyl intermediate 3f

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obtained from 2,4-dihydroxybenzaldehyde (1a) in two steps with an overall yield of 15% (Table
2). The construction of five (14) and six (15) membered cyclic compounds was carried out from
3f using insitu epoxidation followed by cyclization. For the synthesis of moracin O (6),
epoxidation with m-CPBA followed by [5-exo-tet]-cyclization under basic condition gave mixture
of 14 and 15 in a ratio of 3:1, which were then separated by column chromatography. Although in
situ epoxidation with m-CPBA followed by ring closure under acidic conditions (p-TSA) has been
reported to give six-membered cyclic compound 15,3a selective [6-endo-trig]-closure was also
observed without using an acid catalyst to yield 15 as the sole product when we employed oxone
for the epoxidation. From these two intermediates (14 and 15), direct Suzuki coupling with 13
afforded (±) moracins O (6) and P (7) in five steps with overall yields of 6.8% and 9.2%,
respectively.
OH
c
a
Br
O
O
HO
O
O
HO
OH
14
(±) Moracin O (6)
Br
O
HO
2e
OH
OH
HO
HO
b
c
Br
O
O
O
O
15
(±) Moracin P (7)
Scheme 3. The synthesis of moracins O (6) and P (7). Reagents and conditions: (a) i) m-CPBA,
DCM, 0 °C to rt; ii) LiOH, MeOH, rt, 1 h, 57%; (b) oxone, ACN:H2O (4:1), rt, 3 h, 76%; (c)
boronic ester 13, K3PO4, Pd(dppf)Cl2.DCM, DMF:H2O (4:1), 70 °C, 1 h, 80% (6) and 81% (7).

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Gramniphenols F (8) and G (9) exhibiting anti-tobacco mosaic virus activity isolated from the
plant Arundina Graminfolia12 and morunigrol C (10) isolated from the bark of Morus nigra13 have
already been synthesized.5b,6b Owing to their structural similarity to moracin P, we planned a
unified route for these natural products from 3f. Initial attempts using BF3.Et2O cyclization
followed by DDQ oxidation yielded desired intermediate 17 in low yield.14a–c Hence, to improve
the yield, an alternate route involving the already established intermediate 15 was designed. The
dehydration of 15 under Appel conditions gave 17 in good yield.15 After the successful generation
of benzofuran 17, it was directly coupled with the corresponding boronic esters (13 and 18–20) to
give natural products gramniphenols F (8) and G (9), morunigrol C (10), and 3',5'-di-O-methyl
morunigrol C (11) with overall yields of 7.3%, 7.8%, 7.3%, and 7.8% respectively (Scheme 4).
a
b
Br
O
Route 1
O
16
R1
R1
e
Br
Br
R2
O
O
HO
O
O
O
2e
17
Gramniphenol F (8): R1 = H, R2 = OH
Gramniphenol G (9): R1 = H, R2 = OMe
Murunigrol C (10): R1 = OH, R2 = H
3',5'-di-O-methyl
HO
d
c
Br
Route 2
O
O
morunigrol C (11): R1 = OMe, R2 = H
15
O
O
O
O
O
B
OH
B
B
O
O
O
20
O
19
18
Scheme 4. The synthesis of gramniphenols F (8) and G (9), morunigrol C (10) and 3’,5’-di-O-
methyl morunigrol C (11). Reagents and conditions: (a) BF3.Et2O, DCE, rt, 2 h, 50%; (b) DDQ,

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dioxane, 16 h, 100 °C, 37%; (c) oxone, ACN:H2O (4:1), rt, 3 h, 76%; (d) PPh3, CCl4:ACN (1:1),
80 °C, 85%; (e) boronic esters (13 and 18–20), K3PO4, Pd(dppf)Cl2.DCM, DMF:H2O (4:1), 1 h,
70 °C, 76% (8), 80% (9), 75% (10), and 80% (11).
Conclusions
In conclusion, we report the improved and divergent synthesis of moracins M (4), N (5), O (6), P
(7), gramniphenols F (8) and G (9), morunigrol C (10), and its derivative (11). A common pooled
strategy for benzofuran compounds using an efficient one-pot synthesis of versatile intermediate
2-bromo-6-hydroxybenzofurans was successfully established. The fewer number of steps and the
broad substrate scope in this strategy provides a new and practical straightforward route to
numerous benzofuran-based natural products and their derivatives via transition-metal-catalyzed
cross-coupling reactions.
Experimental section
All the commercial chemicals were of reagent grade and were used without further purification.
Solvents were dried with standard procedures. All the reactions were carried out under an
atmosphere of dried argon in flame-dried glassware. Melting points were measured on Thermo
Scientific-9200 apparatus. Infrared (IR) spectra were recorded on an FT-IR Nicolet iS5
spectrometer (ThermoFisher Scientific, Madison, WI, U.S.A.). The proton nuclear magnetic
resonance (1H-NMR) spectra were determined on a Varian (400 or 600 MHz) spectrometer (Varian
Medical Systems, Inc., Palo Alto, CA, USA). 13C-NMR spectra were recorded on a Varian (100
or 150 MHz) spectrometer. The chemical shifts are provided in parts per million (ppm) downfield

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with coupling constants in hertz (Hz). The mass spectra were recorded using high-resolution mass
spectrometry (HRMS) (electron ionization MS) obtained on a JMS-700 mass spectrometer (Jeol,
Japan). The products from all of the reactions were purified by flash column chromatography using
silica gel 60 (230−400 mesh Kieselgel 60). Additionally, thin layer chromatography on 0.25 mm
silica plates (E. Merck; silica gel 60 F254) was used to monitor reactions. Spots were detected by
viewing under UV light and colorized with charring after dipping in 2,4-DNP or basic KMnO4
solution.
General procedure for the one–pot synthesis of 2-bromo-6-hydroxybenzofurans (3a-m): A
solution of CBr4 (4 equiv) in ACN was added drop wise to a suspension of aldehyde (1 equiv),
PPh3 (4 equiv) and Zn powder (4 equiv) in ACN. The reaction mass was stirred at rt for 30 min
(for 3m reaction mass was stirred at 60 °C for 30 min). NH4Cl (5 equiv) was added to the reaction
mass and stirred vigorously till it becomes a clear solution. To this solution Cs2CO3 (3.5 equiv)
and CuI (5 mol%) were added and the reaction mass was heated to reflux for 3 h. Reaction mixture
was cooled to rt, filtered through celite and concentrated in vacuo. Residue was purified by silica
gel column chromatography (hexane:EtOAc). The isolated compounds were stored at 0-5 °C.
2-Bromobenzofuran-6-ol (3a). Purification by silica gel column chromatography (0 to 10%
1
EtOAc in hexane) afforded 3a (0.21 g, 65%) as off white solid. H NMR (400 MHz, CDCl3) δ
7.32 (d, J = 8.4 Hz, 1H), 6.94 (d, J = 2.0 Hz, 1H), 6.77 (dd, J = 8.4, 2.0 Hz, 1H), 6.63 (s, 1H), 4.91
(s, 1H); 13C NMR (100 MHz, CDCl3) δ 156.36, 153.33, 126.29, 122.34, 120.32, 112.37, 108.01,
98.16; IR (neat) νmax 3372.41, 1626.09, 1491.58, 1060.09, 592.17 cm-1; HRMS (ESI) m/z calcd for
C8H6BrO2 [M +H]+ 212.9551; found 212.9545.

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2-Bromo-4-methylbenzofuran-6-ol (3b). Purification by silica gel column chromatography (0 to
10% EtOAc in hexane) afforded 3b (0.22 g, 65%) as off white solid. 1H NMR (400 MHz, DMSO-
d6) δ 9.59 (brs, 1H), 7.00 (s, 1H), 6.73 (d, J = 2.0 Hz, 1H), 6.57 (d, J = 2.0 Hz, 1H), 2.34 (s, 3H);
13C NMR (100 MHz, DMSO-d6) δ 156.42, 155.89, 130.82, 124.33, 120.67, 113.55, 107.71, 95.26,
18.55; IR (neat) νmax 3195.48, 1603.56, 1494.46, 1039.63, 587.22 cm-1; HRMS (ESI) m/z calcd for
C9H8BrO2 [M +H]+ 226.9708; found 226.9709.
2-Bromo-4-methoxybenzofuran-6-ol (3c). Purification by silica gel column chromatography (0
1
to 10% EtOAc in hexane) afforded 3c (0.25 g, 69%) as off white solid. H NMR (400 MHz,
DMSO-d6) δ 9.68 (s, 1H), 6.89 (s, 1H), 6.53 (d, J = 1.6 Hz, 1H), 6.30 (d, J = 1.6 Hz, 1H), 3.82 (s,
3H); 13C NMR (100 MHz, DMSO-d6) δ 157.35, 157.19, 152.63, 123.28, 110.79, 106.10, 95.57,
90.71, 55.89; IR (neat) νmax 3232.65, 1621.99, 1498.11, 1136.41, 1059.60, 538.91 cm-1; HRMS
(ESI) m/z calcd for C9H8BrO3 [M +H]+ 242.9657; found 242.9653.
2-Bromo-7-(3-methylbut-2-en-1-yl)benzofuran-6-ol (3d). Purification by silica gel column
chromatography (0 to 8% EtOAc in hexane) afforded 3d (0.25 g, 59%) as white solid. 1H NMR
(600 MHz, CDCl3) δ 7.19 (d, J = 7.8 Hz, 1H), 6.76 (d, J = 7.8 Hz, 1H), 6.62 (s, 1H), 5.34 (t, J =
7.2 Hz, 1H), 5.25 (s, 1H) 3.62 (d, J = 7.2 Hz, 2H), 1.85 (s, 3H), 1.77 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ 154.91, 152.06, 135.72, 125.97, 121.91, 120.62, 117.67, 112.95, 110.33, 108.42, 25.78,
23.00, 17.93; IR (neat) νmax 3340.70, 2969.76, 2919.09, 1619.64, 1416.49, 1062.25, 909.08, 535.93
cm-1; HRMS (ESI) m/z calcd for C13H14BrO2 [M+H]+ 281.0177; found 281.0185.

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7-Allyl-2-bromobenzofuran-6-ol (3e). Purification by silica gel column chromatography (0 to 9%
EtOAc in hexane) afforded 3e (0.23 g, 60%) as white solid. 1H NMR (400 MHz, CDCl3) δ 7.22
(d, J = 8.0 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.63(s, 1H), 6.10–6.00(m, 1H), 5.21 (dd, J = 16.0,
2.8 Hz, 1H), 5.18 (dd, J = 10.0, 2.8 Hz, 1H), 5.05(s, 1H), 3.67(d, J = 6.4 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ 154.98, 151.81, 135.03, 126.15, 122.09, 118.12, 116.69, 112.94, 108.79, 108.49,
28.06; IR (neat) νmax 3445.22, 1622.31, 1413.76, 1147.33, 1058.01, 905.19, 546.09 cm-1; HRMS
(ESI) m/z calcd for C11 H10 O2 Br [M+H]+ 252.9864; found 252.9865.
2-Bromo-5-(3-methylbut-2-en-1-yl)benzofuran-6-ol (3f). The reaction was carried out in
ACN:DCM (4:1) mixture. Purification by silica gel column chromatography (0 to 7% EtOAc in
hexane) afforded 3f (0.17 g, 40%) as light yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.18 (s, 1H),
6.92 (s, 1H), 6.58 (s, 1H),5.31(t, J = 6.8 Hz, 1H), 5.21 (s, 1H), 3.40(d, J = 6.8 Hz, 2H),1.79(s, 6H);
13C NMR (100 MHz, CDCl3) δ 155.21, 152.29, 135.11, 125.80, 123.92, 122.08, 121.82, 119.98,
107.84, 98.36, 29.96, 25.81, 17.88; IR (neat) νmax 3449.06, 2978.02, 2910.2, 1625.54, 1447.90,
1063.06, 913.82, 596.64 cm-1; HRMS (ESI) m/z calcd for C13H14BrO2 [M+H]+ 281.0177; found
281.0164.
5-Allyl-2-bromobenzofuran-6-ol (3g). Purification by silica gel column chromatography (0 to 12%
1
EtOAc in hexane) afforded 3g (0.16 g, 42%) as light yellow oil. H NMR (400 MHz, CDCl3) δ
7.21 (s, 1H), 6.95 (s, 1H), 6.60 (s, 1H), 6.07–5.98 (m, 1H), 5.18 (dd, J = 10.0, 2.8 Hz, 1H), 5.14
(dd, J = 16.0, 2.8 Hz, 1H), 5.05(s, 1H),3.47(d, J = 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
155.6, 152.02, 136.41, 126.07, 122.34, 122.20, 120.60, 116.75, 107.82, 98.57, 35.37; IR (neat)

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νmax 3416.07, 1625.31, 1469.27, 1238.50, 1085.9, 913.72, 596.74 cm-1; HRMS (ESI) m/z calcd for
C11 H10 O2 Br [M+H]+ 252.9864; found 252.9875.
2-Bromo-5-nitrobenzofuran-6-ol (3h). Purification by silica gel column chromatography (100%
hexane) afforded 3h (39.0 mg, 10%) as yellow solid. 1H NMR (400 MHz, CDCl3) δ 10.72 (s, 1H),
13
8.31 (s, 1H), 7.17 (s, 1H), 6.74 (s, 1H); C NMR (100 MHz, CDCl3) δ 160.16, 153.54, 130.94,
122.49, 116.96, 108.37, 108.38, 100.91; IR (neat) νmax 3115.45, 1633.72, 1526.84, 1426.00,
1324.54, 1128.61, 892.62, 598.32 cm-1; HRMS (ESI) m/z calcd for C8H4NO4NaBr [M+Na]+
279.9221; found 279.9224.
2,5-dibromobenzofuran-6-ol (3i). Purification by silica gel column chromatography (0 to 5%
EtOAc in hexane) afforded 3i (0.19 g, 44%) as off white solid. 1H NMR (400 MHz, CDCl3) δ 7.59
(s, 1H), 7.14 (s, 1H), 6.60 (s, 1H), 5.55 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 155.80, 149.49,
127.70, 123.40, 122.08, 107.31, 106.74, 98.75; IR (neat) νmax 3464.27, 1620.83, 1421.22, 1339.33,
1259.03, 1064.98, 914.44, 596.39 cm-1; HRMS (ESI) m/z calcd for C8H5Br2O2 [M+H]+ 290.8656;
found 290.8651.
2,4-dibromobenzofuran-6-ol (3j). Purification by silica gel column chromatography (0 to 5%
EtOAc in hexane) afforded 3j (0.25 g, 56%) as off white solid. 1H NMR (400 MHz, DMSO-d6) δ
13
10.11 (brs, 1H), 6.98 (s, 2H), 6.93 (s, 1H); C NMR (100 MHz, DMSO-d6) δ 156.70, 156.22,
126.81, 122.09, 116.04, 112.10, 108.35, 97.74; IR (neat) νmax 3334.94, 1591.79, 1406.95, 1281.90,
1082.45, 915.20, 597.64 cm-1; HRMS (ESI) m/z calcd for C8H5Br2O2 [M+H]+ 290.8656; found
290.8651.

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2-Bromo-5-chlorobenzofuran-6-ol (3k). Purification by silica gel column chromatography (0 to
7% EtOAc in hexane) afforded 3k (0.15 g, 40%) as off white solid. 1H NMR (400 MHz, CDCl3)
13
δ 7.44 (s, 1H), 7.13 (s, 1H), 6.60 (s, 1H), 5.58 (s, 1H); C NMR (100 MHz, CDCl3) δ 155.14,
148.78, 127.67, 122.71, 119.15, 116.84, 107.55, 98.84; IR (neat) νmax 3444.81, 1541.95, 1424.59,
1339.32, 1258.90, 1067.59, 788.93, 597.00 cm-1; HRMS (ESI) m/z calcd for C8H5BrClO2 [M+H]+
246.9161; found.246.9154.
2-Bromo-5,7-dichlorobenzofuran-6-ol (3l). Purification by silica gel column chromatography (0
to 10% EtOAc in hexane) afforded 3l (0.19 g, 44%) asoff white solid. 1H NMR (400 MHz, CDCl3)
δ 7.40 (s, 1H), 6.66 (s, 1H), 5.82 (brs, 1H); 13C NMR (100 MHz, CDCl3) δ 151.01, 145.41, 128.52,
122.55, 117.82, 117.60, 108.31, 104.17; IR (neat) νmax 3461.15, 1542.30, 1413.92, 1345.58,
1149.97, 1066.24, 798.10, 730.68, 596.73 cm-1; HRMS (ESI) m/z calcd for C8H4BrCl2O2 [M +H]+
280.8772; found.280.8763.
2-Bromo-3-methylbenzofuran-6-ol (3m). The reaction was carried out in ACN:DCM (4:1)
mixture. Purification by silica gel column chromatography (0 to 10% EtOAc in hexane) afforded
3m (0.14 g, 40%) as off white semi solid (Thermally unstable and rapidly decomposing on
complete drying). 1H NMR (400 MHz, DMSO-d6) δ 9.64 (brs, 1H), 7.34 (d, J = 8.0 Hz, 1H), 6.88
(d, J = 2.0 Hz,1H), 6.75 (dd, J = 8.0, 2.8 Hz, 1H), 2.10 (s, 3H). 13C NMR (100 MHz, DMSO-d6)
δ 156.13, 155.89, 123.24, 121.30, 119.70, 115.38, 112.77, 97.83, 8.84 IR (neat) νmax 3363.92,
1625.57, 1489.33, 1251.12, 1079.32, 628.82 cm-1; HRMS (ESI) m/z calcd for C9H8BrO2 [M +H]+
226.9708; found 226.9707.

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5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene-1,3-diol (13). Pd(dppf)Cl2.DCM (0.19
g, 0.27 mmol) was added to a degassed solution of 5-bromobenzene-1,3-diol (12) (1.00 g, 5.32
mmol), bis(pinacolato)diboron (2.02 g, 7.98 mmol) and KOAc (0.89 g, 7.98 mmol) in 1,4-
dioxane.The reaction mass was heated to 100 °C for 2 h. Reaction mass was cooled to rt, filtered
through celite and concentrated in vacuo. Purification by silica gel column chromatography (0 to
25% EtOAc in hexane) afforded 13 (1.10 g, 88%) as off white solid. m.p. 224–226 °C; 1H NMR
(400 MHz, DMSO-d6) δ 9.13 (brs, 2H), 6.53 (d, J = 2.0 Hz, 2H), 6.53 (d, J = 2.0 Hz, 1H), 1.25 (s,
13
12H); C NMR (100 MHz, DMSO-d6) δ 158.46, 112.46, 105.98, 83.77, 25.09; IR (neat) νmax
3326.11, 2967.44, 1606.18, 1377.39, 1139.65, 1010.68 cm-1; HRMS (ESI) m/z calcd for
C12H18BO4 [M +H]+ 237.1298; found 237.1304.
2-(6-bromo-2,3-dihydrobenzo[1,2-b:5,4-b']difuran-2-yl)propan-2-ol
(14).
3-
Chloroperoxybenzoic acid (0.14 g, 0.80 mmol) was added to a solution of 2-bromo-5-(3-
methylbut-2-en-1-yl)benzofuran-6-ol (3f) (0.15 g, 0.53 mmol) in DCM at 0 °C and the mixture
was stirred for 0.5 h. Reaction mass distilled to dryness, residue was re-dissolved in MeOH and
LiOH (38.0 mg, 1.60 mmol) was added to it. Resulting mixture was stirred at rt for another 2 h.
Reaction mass was distilled to dryness, partitioned between EtOAc and water. Organic layers
washed with brine, dried over sodium sulfate and concentrated in vacuo. Purification by silica gel
column chromatography (0 to 8% EtOAc in hexane) afforded 14 (90.0 mg, 57%) asoff white solid.
m.p. 80–83 °C; 1H NMR (400 MHz, CDCl3) δ 7.20 (s, 1H), 6.86 (s, 1H), 6.58 (s, 1H), 4.66 (t, J =
13
8.8 Hz, 1H), 3.25–3.15 (m, 2H), 1.89(s, 1H), 1.35 (s, 3H), 1.22 (s, 3H); C NMR (100 MHz,
CDCl3) δ 157.73, 155.78, 125.37, 123.96, 122.26, 115.18, 108.07, 92.85, 90.25, 71.78, 30.25,

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26.19, 24.03; IR (neat) νmax.3195.46, 2916.58, 1603.56, 1494.46, 1301.76, 1120.02,
1039.63,567.22 cm-1; HRMS (ESI) m/z calcd for C13H14BrO3 [M+H]+ 297.0126; found 297.0139.
2-Bromo-7,7-dimethyl-6,7-dihydro-5H-furo[3,2-g]chromen-6-ol (15).
Oxone (0.22 g, 1.42 mmol) was added to a solution of 2-bromo-5-(3-methylbut-2-en-1-
yl)benzofuran-6-ol (3f) (0.20 g, 0.71 mmol) in ACN:H2O (4:1) at 0 °C and the mixture was stirred
for 3h slowly raising to rt. Reaction mass was partitioned between EtOAc and water. Organic
layers washed with brine, dried over sodium sulfate and concentrated in vacuo. Purification by
silica gel column chromatography (0 to 10% EtOAc in hexane) afforded 15 (0.16 g, 76%) as off
white solid. m.p. 96–99 °C; 1H NMR (400 MHz, CDCl3) δ 7.15 (s, 1H), 6.93 (s, 1H), 6.57 (s, 1H),
3.85–3.80 (m, 1H), 3.15 (dd, J = 16.4, 5.6 Hz, 1H), 2.86 (dd, J = 16.4, 5.6 Hz, 1H), 1.74 (d, J =
13
7.6 Hz, 1H), 1.37 (s, 3H), 1.33 (s, 3H); C NMR (100 MHz, CDCl3) δ 155.44, 150.69, 126.51,
122.60, 120.17, 115.56, 107.54, 104.52, 99.44, 69.62, 31.54, 24.75, 22.20; IR (neat) νmax 3375.57,
2971.8, 2924.96, 1630.96, 1457.67, 1142.50, 1101.77, 1049.94, 594.62 cm-1; HRMS (ESI) m/z
calcd for C13H14BrO3 [M +H]+ 297.0126; found 297.0165.
2-Bromo-7,7-dimethyl-6,7-dihydro-5H-furo[3,2-g]chromene (16). BF3.Et2O (45.0 mg, 0.31
mmol) was added to a solution of 2-bromo-5-(3-methylbut-2-en-1-yl)benzofuran-6-ol (3f) (60.0
mg, 0.21 mmol) in DCE at 0°C and the mixture was stirred for 1 h. Reaction mass was partitioned
between DCM and saturated NaHCO3 solution. Organic layers washed with brine, dried over
sodium sulfate and concentrated in vacuo. Purification by silica gel column chromatography (100%
hexane) afforded 16 (35.0 mg, 59%) as colourless oil. 1H NMR (400 MHz, CDCl3) δ 7.12 (s, 1H),

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6.86 (s, 1H), 6.54 (s, 1H), 2.85 (t, J = 6.8 Hz, 2H), 1.82 (t, J = 6.8 Hz, 2H), 1.39 (s, 6H); 13C NMR
(100 MHz, CDCl3) δ 155.54, 152.00, 125.86, 121.66, 119.36, 117.72, 107.50, 99.21, 74.48, 32.84,
26.83, 22.67; HRMS (ESI) m/z calcd for C13H14BrO2 [M +H]+ 281.0177; found 281.0174.
2-Bromo-7,7-dimethyl-7H-furo[3,2-g]chromene (17). PPh3 (0.18 g, 0.68 mmol) was added to a
solution of 2-bromo-7,7-dimethyl-6,7-dihydro-5H-furo[3,2-g]chromene (15) (0.1 g, 0.34 mmol)
in ACN:CCl4 (1:1) and the reaction mixture was heated to 80 °C for 1h. Reaction mass was cooled
to rt and concentrated in vacuo. Purification by silica gel column chromatography (100% hexane)
afforded 17 (80.0 mg, 85%) as colourless oil. 1H NMR (400 MHz, CDCl3) δ 7.05 (s, 1H), 6.88 (s,
1H), 6.57 (s, 1H), 6.38 (d, J = 10.0 Hz, 1H), 5.63 (d, J = 10.0 Hz, 1H), 1.43 (s, 6H); 13C NMR (100
MHz, CDCl3) δ 156.20, 151.23, 130.51, 126.07, 122.44, 122.30, 118.61, 116.74, 107.99, 99.48,
76.37, 27.78; IR (neat) νmax 2974.28, 2934.57, 1625.79, 1541.61, 1462.62, 1263.54,1113.53,
914.89, 590.72 cm-1; HRMS (ESI) m/z calcd for C13H12BrO2 [M+H]+ 279.0021; found 279.0019.
General Procedure for Suzuki Coupling: Pd(dppf)Cl2.DCM (5 mol%) was added to a degassed
solution of aryl bromide (1 equiv), boronic ester/acid (1.2 equiv) and K3PO4 (2.0 equiv) in
DMF:H2O (4:1). The reaction mixture was heated 70 °C for 1 h. Reaction mass was cooled to rt,
filtered through celite and partitioned between EtOAc and water. Organic layers washed with brine,
dried over sodium sulfate and concentrated in vacuo. Residue was purified by silica gel column
chromatography (hexane:EtOAc).
Moracin M (4). Purification by silica gel column chromatography (0 to 55% EtOAc in hexane)
afforded 4 (45.0 mg, 83%) as off white solid. m.p. 264–266 °C; 1H NMR (400 MHz, DMSO-d6) δ

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9.44 (brs, 3H), 7.38 (d, J = 8.0 Hz, 1H), 7.08 (s, 1H), 6.92 (d, J = 2.0 Hz, 1H), 6.74 (dd, J = 8.4,
2.0 Hz, 1H), 6.68 (d, J = 2.0 Hz, 2H), 6.21 (t, J = 2.0 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ
159.22, 156.16, 155.68, 154.38, 132.10, 121.56, 121.21, 112.88, 103.06, 102.72, 101.99, 97.89.
IR (neat) νmax 3252.77, 1604.30, 435.61, 1351.42, 1138.01, 1000.09, 814.45 cm-1; HRMS (ESI)
m/z calcd for C14H11O4 [M +H]+ 243.0658; found 243.0567.
Moracin N (5). Purification by silica gel column chromatography (0 to 40% EtOAc in hexane)
afforded 5 (25.0 mg, 51%) as off white solid. m.p. 183–185 °C; 1H NMR (600 MHz, Methanol-d4)
δ 7.18 (s, 1H), 6.87(s, 1H), 6.85 (s, 1H), 6.74 (s, 2H), 6.22 (s, 2H), 5.35 (t, J = 7.8 Hz, 1H), 3.33
(d, J = 7.8 Hz, 2H), 1.74 (s, 3H), 1.72 (s, 3H);13C NMR (150 MHz, Methanol-d4) δ 158.49, 154.29,
154.13, 153.18, 132.59, 131.38, 124.75, 122.98, 121.33, 119.97, 102.41, 101.90, 100.81, 96.42,
28.08, 24.55, 16.39; IR (neat) νmax 3283.67, 2967.36, 2911.33, 1599.06, 1467.32, 1352.85, 1147.58,
1091.58 cm-1; HRMS (ESI) m/z calcd for C19H19O4 [M+H]+ 311.1283; found 311.1281.
Moracin O (6). Purification by silica gel column chromatography (0 to 50% EtOAc in hexane)
afforded 6 (26.0 mg, 80%) as off white solid. m.p. 235–237 °C; 1H NMR (400 MHz, Methanol-
d4) δ 7.29 (s, 1H), 6.89(s, 1H), 6.85 (s, 1H), 6.73 (d, J = 2.4 Hz, 2H), 6.22 (t, J = 2.4 Hz, 1H), 4.64
(t, J = 9.2 Hz 1H), 3.23 (d, J = 7.6 Hz 1H), 3.21 (d, J = 8.8 Hz 1H), 1.27 (s, 3H), 1.24 (s, 34); 13C
NMR (100 MHz, Methanol-d4) δ 158.53, 158.43, 154.94, 154.78, 132.40, 123.68, 122.55, 115.56,
102.37, 101.99, 100.93, 91.79, 89.95, 71.08, 29.74, 23.92, 23.83; IR (neat) νmax 3325.14, 2990.35,
1700.68, 1608.44, 1443.51, 1356.31, 1136.63, 1090.87, 997.00, 946.77 cm-1; HRMS (ESI) m/z
calcd for C19 H19 O5 [M +H]+ 327.1232; found 327.1234.

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Moracin P (7). Purification by silica gel column chromatography (0 to 50% EtOAc in hexane)
afforded 7 (27.0 mg, 81%) as off white solid. m.p. 133–136 °C; 1H NMR (400 MHz, Methanol-
d4) δ 7.22 (s, 1H), 6.88 (s, 1H), 6.85 (s, 1H), 6.75 (d, J = 2.4 Hz, 2H), 6.24 (t, J = 2.0 Hz, 1H), 3.78
(dd, J = 7.6, 5.6 Hz,1H), 3.11 (dd, J = 16.4, 5.2 Hz, 1H), 2.82 (dd, J = 16.8, 7.6 Hz, 1H), 1.27 (s,
3H), 1.23 (s, 3H); 13C NMR (100 MHz, Methanol-d4) δ 160.01, 156.63, 155.96, 152.60, 133.74,
124.24, 121.82, 117.73, 104.04, 103.69, 101.85, 99.72, 78.26, 70.64, 32.48, 26.03, 21.12; IR (neat)
νmax 3319.02, 2922.89, 1604.03, 1459.38, 1351.54, 1139.25, 1104.48, 1053.26, 1000.74, 944.82
cm-1; HRMS (ESI) m/z calcd for C19 H19 O5 [M +H]+ 327.1232; found 327.1243.
Gramniphenol F (8). Purification by silica gel column chromatography (0 to 10% EtOAc in
1
hexane) afforded 8 (20.0 mg, 76%) as off white solid. m.p. 168–170 °C; H NMR (400 MHz,
Methanol-d4) δ 7.64 (d, J = 7.2 Hz, 2H), 7.11 (s, 1H), 6.85 (s, 1H), 6.84 (d, J = 7.2 Hz, 2H), 6.79
13
(s, 1H), 6.42 (d, J = 9.6 Hz, 1H), 5.66 (d, J = 9.6 Hz, 1H), 1.41 (s, 6H); C NMR (100 MHz,
Methanol-d4) δ 155.56, 155.34, 155.22, 151.10, 129.92, 126.19, 123.86, 123.07, 122.84, 118.17,
117.31, 115.68, 99.48, 76.24, 27.79; IR (neat) νmax 3419.52, 2968.90, 2931.59, 1573.74, 1506.67,
1346.82,1236.92, 1125.88 cm-1; HRMS (ESI) m/z calcd for C19H17O3 [M+H]+ 293.1178; found
293.1166.
Gramniphenol G (9). Purification by silica gel column chromatography (0 to 10% EtOAc in
hexane) afforded 9 (22.0 mg, 80%) as off white solid. m.p. 179–181 °C; 1H NMR (400 MHz,
CDCl3) δ 7.72 (d, J = 9.2 Hz, 2H), 7.10 (s, 1H), 6.95 (d, J = 9.2 Hz, 2H), 6.94 (s, 1H), 6.74 (s, 1H),
13
6.41 (d, J = 10.0 Hz, 1H), 5.62 (d, J = 10.0 Hz, 1H), 3.84 (s, 3H), 1.45 (s, 6H); C NMR (100
MHz, CDCl3) δ 159.62, 155.36, 151.07, 129.89, 125.95, 123.57, 123.12, 122.85, 118.15, 117.28,

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DOI: 10.1039/C8OB03102A
114.21, 99.49, 76.21, 55.37, 27.79; IR (neat) νmax 2976.04, 2934.13, 16.15.14, 1586.95, 1503.59,
1458.24, 1246.13, 1123.40, 1033.06 cm-1; HRMS (ESI) m/z calcd for C20H19O3 [M+H]+ 307.1334;
found 307.1332.
Morunigrol C (10). Purification by silica gel column chromatography (0 to 20% EtOAc in hexane)
afforded 10 (26.0 mg, 75%) as off white solid. m.p. 104–106 °C; 1H NMR (600 MHz, Methanol-
d4) δ 7.16 (s, 1H), 6.90 (s, 1H), 6.85 (s, 1H), 6.74 (s, 2H), 6.44 (d, J = 10.2 Hz, 1H), 6.24 (s, 1H),
13
5.68 (d, J = 10.2 Hz, 1H), 1.42 (s, 6H); C NMR (150 MHz, Methanol-d4) δ 158.61, 155.36,
151.39, 132.10, 129.69, 122.85, 122.33, 118.31, 117.34, 102.56, 102.29, 100.75, 98.52, 75.95,
26.65; IR (neat) νmax 3269.50, 2973.95, 1612.61, 1350.62, 1122.38 cm-1; HRMS (ESI) m/z calcd
for C19H17O4 [M +H]+ 309.1127; found 309.1118.
3',5'-di-O-methylmorunigrol C (11). Purification by silica gel column chromatography (0 to 5%
EtOAc in hexane) afforded 11 (24.0 mg, 80%) as off white solid. m.p. 115–117 °C; 1H NMR (400
MHz, CDCl3) δ 7.13 (s, 1H), 6.96 (s, 1H), 6.95 (d, J = 2.0 Hz, 2H), 6.87 (s, 1H), 6.43 (t, J = 2.0
Hz, 1H), 6.41 (d, J = 9.6 Hz, 1H), 5.63 (d, J = 9.6 Hz, 1H), 3.86 (s, 6H), 1.45 (s, 6H); 13C NMR
(100 MHz, CDCl3) δ 161.09, 155.51, 154.99, 151.61, 132.38, 130.09, 122.76, 118.37, 117.64,
102.59, 101.70, 100.61, 99.54, 76.33, 55.51, 27.83; IR (neat) νmax 2965.38, 2929.18, 1596.99,
1574.19, 1452.45, 1345.99, 1120.26 cm-1; HRMS (ESI) m/z calcd for C21H21O4 [M+H]+ 337.1440;
found 337.1423.

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DOI: 10.1039/C8OB03102A
Conflicts of interest
“There are no conflicts to declare”.
Acknowledgments
This work was supported by the National Research Foundation of Korea (NRF) grant funded by
the Korea government (MSIT) (NRF 2018R1A5A2023127).

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DOI: 10.1039/C8OB03102A
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