Total synthesis of the pyranocoumaronochromone lupinalbin H

Article abstract of DOI:10.1016/j.tet.2011.09.042

The pyranocoumaronochromone lupinalbin H was synthesized in three major steps, which involved preparation of 2′-hydroxygenistein by the Suzuki-Miyaura reaction, followed by oxidative cyclodehydrogenation into lupinalbin A. The final step was the regiospec

Full text of DOI:10.1016/j.tet.2011.09.042

Tetrahedron 67 (2011) 8654e8658
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Total synthesis of the pyranocoumaronochromone lupinalbin H
*
Mamoalosi A. Selepe, Siegfried E. Drewes, Fanie R. van Heerden
School of Chemistry, University of KwaZulu-Natal, Private Bag X01, Scottsville 3209, Pietermaritzburg, South Africa
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 July 2011
Received in revised form 30 August 2011
Accepted 12 September 2011
Available online 17 September 2011
The pyranocoumaronochromone lupinalbin H was synthesized in three major steps, which involved
preparation of 20-hydroxygenistein by the SuzukieMiyaura reaction, followed by oxidative cyclo-
dehydrogenation into lupinalbin A. The final step was the regiospecific introduction of the dimethylpyran
moiety to ring A of lupinalbin A via an aldol-type condensation with 3-methyl-2-butenal and 6
electrocyclization.
p-
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Lupinalbin H
Lupinalbin A
Pyranocoumaronochromone
Isoflavonoid
20-Hydroxygenistein
SuzukieMiyaura reaction
1. Introduction
Despite the numerous synthetic procedures that have been de-
veloped for the dimethylpyran moiety, the regioselective in-
troduction of the dimethylpyran system to the synthetic precursors
or tothe coumaronochromone core has been a majorchallenge in the
synthesis of pyranocoumaronochromones.14,15
Coumaronochromones are a subclass of isoflavonoids with gen-
eral structure 1.1 They have been isolated from different plant genera,
mostlyof the Leguminosae,1e5 although a fewcoumaronochromones
have been reported from non-leguminous plants.6e8 The striking
feature of most naturally-occurring coumaronochromones is the
presence of prenyl side chains, which in most instances are cyclized
to adjacent hydroxy groups to give pyrano or furano rings.1e3,5,7,9,10
Most pyranocoumaronochromones exhibit important biological ac-
tivities, such as anthelminthic, oestrogenic, neuroprotective, anti-
platelet aggregation, anti-HIV, immunosuppressive activities as well
as cytotoxicity against certain cancer cell lines.2,3,5,9e13 Despite their
biological importance, the synthesis of these compounds has re-
ceived little attention. Methods, which have been employed for the
synthesis of the coumaronochromone nucleus are photochemical
contraction of rotenoids and oxidative cyclization of 20-hydroxyiso-
flavones, the latter being the strategy employed mostly.14e16 The
dimethylpyran scaffold, on the other hand, can be accessed via sev-
eral synthetic approaches, which involve cycloaddition reactions of
C-prenylated phenols, aldol-type condensation of phenols with
prenal (3-methyl-2-butenal) or prenal acetal, dehydration of chro-
manols, HarfenisteThom rearrangement of propargyl ethers and
one-pot Wittig reactions of o-naphthoquinones with allyl-
triphenylphosphonium salts and subsequent electrocyclization.17e20
O
O
O
1
1
8''
8
O
O
2
3
8a
4a
O
7''
2'
6''
5''
A
C
B
OH
5
OH
4''
4'
O
6'
2
In continuation of our studies on the regioselective synthesis of
pyranoisoflavonoids,21 the present paper reports the first total
synthesis of lupinalbin H (2) and confirmation of its structure on
the basis of 1D and 2D NMR techniques. Lupinalbin H (2) was iso-
lated together with other flavonoids from the methanolic extract of
the roots of yellow lupin (Lupinus luteus cv Topaz) by Tahara et al.22
The assignment of the structure of 2 was based mainly on com-
parison of its 1H NMR signals with those of related compounds and
the 13C NMR data was not reported. Furthermore, the other flavo-
noids isolated along with it were reported to exhibit antifungal
activity; however, 2 was not assayed for its activity. The lack of
detailed structural characterization and bioactivity studies of
lupinalbin H (2) can be attributed to the low quantity obtained from
* Corresponding author. Tel.: þ27 33 2605886; fax: þ27 33 2605009; e-mail
address: vanheerdenf@ukzn.ac.za (F.R. van Heerden).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.09.042

M.A. Selepe et al. / Tetrahedron 67 (2011) 8654e8658
8655
the plant source.22 Therefore, our aim was to develop a synthetic
route that can readily give access to 2 in a good yield, to confirm its
structure unambiguously and provide material for future biological
studies.
With this synthesis we hope to demonstrate the usefulness of
the SuzukieMiyaura reaction in the synthesis of isoflavonoids.
Previous methods for the synthesis of this class of compounds were
based mainly on chalcones and deoxybenzoins as in-
termediates.14,16 However, the chalcone route depends on the use
of the highly toxic thallium trinitrate whereas the deoxybenzoin
route employs harsh reaction conditions.
prepared and therefore we opted for methoxymethyl as protecting
group in the synthesis of 5. Boronic acid 627 was prepared from
commercially available resorcinol (7), as illustrated in Scheme 2.
Protection of 7 with MOMCl, prepared in situ from the readily
available dimethoxymethane and acetyl chloride,29 rendered
methoxymethyl ether 8 (60%),30 which was regioselectively io-
dinated at C-4 by I2 in the presence of CH3CO2Ag to give an aryl
iodide 9 in 95% yield.31 In our previous investigation, we dem-
onstrated the successful regioselective iodination of a chromanone
21
containing resorcinol moiety using CF3CO2Ag and I2. CH3CO2Ag
gave comparable results in the present case. Other readily avail-
able silver salts (AgNO3 and Ag2SO4) were tested for C-4 iodination
of 8, but rendered 9 in low yields when CHCl3 was used as the
solvent and in moderate yields in EtOH (Table 1).32,33 The aryl
iodide 9 was converted into boronic acid 6 by lithiumeiodine
exchange, followed by immediate in situ nucleophilic attack of the
generated aryl lithium species on triisopropyl borate and hydro-
lysis of the resulting boronate ester with NH4Cl in a one-pot
reaction.34,35
2. Results and discussion
Scheme 1 shows the retrosynthetic analysis of lupinalbin H (2).
Lupinalbin H (2) was planned to be synthesized by the regiospecific
condensation of lupinalbin A (3)23,24 with prenal. Compound 3
could be prepared by oxidative cyclization of 20-hydroxygenistein
(4),25,26 which could readily be accessed by the SuzukieMiyaura
reaction of 3-iodochromone 521 and boronic acid 6.27 The synthesis
of the penultimate precursor 3 from 20-hydroxyisoflavones has
been reported previously.14,16 However, the former syntheses were
based on the deoxybenzoin and the chalcone routes for the con-
struction of the isoflavone core.14,16
Table 1
Preparation of aryl iodide 9 by iodination of 8 with I2 and silver saltsa
Silver salt
AgNO3
Ag2SO4
Solvent
Time (h)
Yieldsb (%)
CHCl3
CHCl3
EtOH
EtOH
CHCl3
5
5
1
1
5
40
35
62
58
95
c
AgNO3
Ag2SO4
c
2
CH3CO2Ag
a
Silver salt (1.2 equiv), 1.1 equiv I2.
Isolated yields.
Ag2SO4 (0.6 equiv), 1.1 equiv I2.
b
c
O
H
HO
HO
O
O
Having successfully synthesized the boronic acid 6, the next step
involved coupling of 6 with 3-iodochromone 521 in the presence of
10% Pd(C) to give an isoflavone 10 (Scheme 3).36 Cleavage of the
MOM protecting groups of 10 under acidic conditions and sub-
sequent oxidation of 20-hydroxygenistein (4) with DDQ afforded
the phytoestrogen lupinalbin A (3)16 in a 66% yield.14 The last step
was regioselective introduction of the dimethylpyran scaffold to
the phloroglucinol moiety of lupinalbin A (3) to give lupinalbin H
(2). This was planned to be achieved by base-catalyzed coupling of
OH
OH
O
3
O
OH
3 with prenal, which proceeds via aldol-type reaction and 6p-
OH
O
4
electrocylization.18 Thus, treatment of the methanolic solution of 3
with Ca(OH)2 and prenal (2.5 equiv) rendered lupinalbin H (2) in
40% yield and 35% of 3 was recovered.37 Addition of a large excess of
prenal (5 equiv) effected complete consumption of 3 as observed on
TLC but required tedious chromatographic isolation of the targeted
product from the reaction mixture due to side products resulting
from the polymerization of prenal.
OH
OMOM
MOMO
O
(HO)2B
+
I
Lupinalbin A (3) has four nucleophilic sites at positions 6, 8, 30
and 50, which can condense with prenal to give multiple products.
As anticipated, the reaction favoured the more nucleophilic
phloroglucinol moiety (ring A) rather than the resorcinol moiety
(ring B). Nevertheless, three possible regioisomers can result from
condensation of prenal with ring A of 3, i.e., the targeted linear
isomer 2 and two angular isomers 11 and 12. From the 1H NMR
results, it could be readily deduced that the isomer 12 was not
OMOM
MOMO
O
5
6
Scheme 1. Retrosynthetic analysis of lupinalbin H (2).
The synthesis of intermediate 5 was described in a previous
paper.21 Vasselin et al.28 reported that with the widely used benzyl
protecting group, the 3-iodobenzopyran-4-one could not be
1. THF/Et2O, B(i-PrO)3
2. n-BuLi
3. NH4Cl
OMOM
OMOM
OH
CH2Cl2, (i-Pr)2EtN
CH3CO2Ag, I2
CHCl3
I
MOMCl
6
OMOM
60%
OMOM
74%
OH
95%
9
8
7
Scheme 2. Synthesis of boronic acid 6.

8656
M.A. Selepe et al. / Tetrahedron 67 (2011) 8654e8658
Pd(C), Na2CO3 MOMO
DME/H2O
O
OMOM
THF, DDQ
66%
CH3OH, HCl
73%
5
6
+
3
4
78%
MOMO
O
CH3OH
OMOM
Ca(OH)2
Prenal
10
O
O
O
2
40%
OH
OH
O
Scheme 3. Total synthesis of lupinalbin H (2).
formed due to the appearance of a signal characteristic for a hy-
drogen-bonded OH at dH 13.38 (1H, OH-5). Furthermore, in the
1H NMR spectrum was present four aromatic protons, which gave
an ABX spin system for ring B protons at dH 7.82 (1H, d, J¼8.3 Hz,
H-60), 7.14 (1H, d, J¼2.0 Hz, H-30), 7.02 (1H, dd, J¼2.0 and 8.3 Hz, H-
50),and a one-proton singlet for the ring A proton at dH 6.54 (H-8).
The dimethylpyran protons displayed a singlet integrating for six
protons at dH 1.48 (2ꢀ CH3) and two one-proton doublets for the
olefinic protons at dH 6.70 (J¼10.0 Hz, H-400) and 5.79 (1H, d,
J¼10.0 Hz, H-500). These 1H NMR results were in agreement with
those reported in the literature for 2.22 The 13C NMR spectrum
displayed 19 carbon resonances, which were identified as two
methyl carbons overlapping at dC 27.3, six methine carbons at dc
128.6, 121.3, 114.6, 113.6, 98.5 and 95.3 and 12 quaternary carbons
at dC 178.6, 164.7, 158.5, 157.0, 156.4, 154.0, 150.4, 114.0, 105.9,
104.0, 97.5 and 80.0 by DEPT and HSQC experiments. From the
HMBC spectrum, the olefinic proton at dH 6.70 (H-400) displayed
correlations to carbon signals at dC 80.0 (C, C-600), 105.9 (C, C-6),
157.0 (C, C-5) and 158.5 (C, C-7) and the aromatic proton at dH 6.54
(H-8) showed connections to carbon resonances at dC 104.0 (C, C-
4a), 105.9 (C, C-6), 154.0 (C, C-8a) and 158.5 (C, C-7) (Fig. 1). From
these correlations, it was confirmed that the dimethylpyran ring
was attached to C-6 and OH-7, giving the targeted product 2 and
not the angular isomer 11. The assignments of the quaternary
carbons on ring B were also based on HMBC correlations. The
proton at dH 7.82 (H-60) displayed correlations to carbon signals at
dC 97.5 (C, C-3), 150.4 (C, C-20) and 156.4 (C, C-40), whereas H-50 (dH
7.02) showed correlations to carbons at dC 114.0 (C, C-10) and 156.4
(C, C-40), and the proton at dH 7.14 (H-30) showed correlations to
signals at dC 114.0 (C, C-10), 150.4 (C, C-20) and 156.4 (C, C-40)
(Fig. 1). The structure of 2 was confirmed by HRMS-ESI, which
gave an m/z peak of 349.0710 [MꢁH]ꢁ, in agreement with the
calculated molecular weight of 349.0712 for C20H13O6.
O
O
O
OH
O
OH
O
11
HO
O
OH
O
O
12
3. Conclusion
In conclusion, lupinalbin H (2) has been successfully synthesized
by a highly convergent route. The synthesis featured the Suzu-
kieMiyaura coupling reaction for the construction of the isoflavone
nucleus in good yields, and a highly regioselective introduction of
the dimethylpyran scaffold to the coumaronochromone core. Fur-
thermore, it gave access to other naturally-occurring phytoes-
trogens, 20-hydroxygenistein (4) and lupinabin A (3). Owing to the
potential pharmacological properties of the pyranocoumar-
onochromones, the development of the practical synthetic route
described herein for lupinalbin H (2) represents a significant ad-
vance towards the synthesis of other structurally related com-
pounds and exploration of their biological properties.
4. Experimental procedures
4.1. General
All moisture-sensitive reactions were performed using dried
anhydrous solvents in oven-dried glassware under an atmosphere
of N2. Hexanes (Hex) used for chromatographic purifications was
distilled prior to use. Reactions were monitored by TLC, performed
on silica gel plates (60 F254) and visualized under UV light. Alter-
natively, detection of spots on the TLC was achieved by heating
with a heat gun after treatment with a solution of anisaldehyde in
concentrated H2SO4 and EtOH prepared in volume ratios 1:1:18,
respectively. Column chromatographic purifications were effected
using silica gel (60 Ǻ, 230e400 mesh). Centrifugal chromatogra-
phy (chromatotron) was performed on glass plates coated with
silica gel with particle size 0.040e0.063 mm, 2e4 mm thick. 1H,
11B, 13C NMR spectra were recorded on 400 or 500 MHz spec-
trometer. DEPT and 2D NMR (COSY, HSQC and HMBC) were used
8
8a
4a
6''
7
O
H
O
O
O
2'
3'
4'
OH
1'
5
OH
5'
H
H
2
O
O
O
O
H
5''
3
6
OH
4''
6'
OH
for assignments of individual protons and carbons resonances. 11
B
H
NMR spectra were referenced against an external standard of neat
BF3.OEt2 containing a capillary tube of acetone-d6 for deuterium
Fig. 1. Key HMBC correlations of (2).

M.A. Selepe et al. / Tetrahedron 67 (2011) 8654e8658
8657
lock. The chemical shifts from 1H NMR and 13C NMR spectra are
reported in parts per million relative to the residual protonated or
deuterated solvents peaks (CDCl3: dH 7.26, dc 77.0; CD3OD: dH 3.31,
dc 49.0 and acetone-d6: dH 2.05, dc 205.1). The mass spectra were
recorded on a time-of-flight mass spectrometer using electrospray
ionisation in the positive or negative mode. IR spectra were
recorded with FT-IR spectrophotometer.
evaporation of the solvent afforded the boronic acid 6 as an orange
soild (2.76 g, 74%): IR (neat) nmax 3385, 2957, 1726, 1603, 1142,
993 cmꢁ1; 1H NMR (CDCl3, 400 MHz)
d
7.79 (1H, d, J¼8.4 Hz, H-6),
6.80 (1H, d, J¼2.0 Hz, H-3), 6.76 (1H, dd, J¼2.0 and 8.4 Hz, H-5),
6.68 (2H, br s, B(OH)2), 5.27 (2H, s, OCH2O), 5.19 (2H, s, OCH2O),
3.50 (3H, s, OCH3), 3.47 (3H, s, OCH3); 13C NMR (CDCl3, 100 MHz)
d
163.5 (C, C-2), 160.9 (C, C-4), 137.8 (CH, C-6), 109.3 (CH, C-5),
102.1 (CH, C-3), 94.6 (OCH2O), 94.0 (OCH2O), 56.4 (OCH3), 56.0
(OCH3), (C-1 signal not observed); 11B NMR (CDCl3, 128 MHz) dB
28.55.
4.2. Synthesis
4.2.1. 1,3-Dimethoxymethoxybenzene (8)30. Catalytic ZnBr2 was
dissolved in dimethoxymethane (16.0 mL, 0.182 mol) under nitro-
gen atmosphere, and then acetyl chloride (12.9 mL, 0.182 mol) was
added dropwise to the stirred solution. The solution was stirred for
an additional 2 h at rt then transferred via a cannula to the ice-cold
solution of resorcinol (7) (5.00 g, 45.4 mmol) and (i-Pr)2EtN
(23.3 mL, 0.136 mol) in CH2Cl2 (100 mL) under a nitrogen atmo-
sphere. The mixture was stirred for 3 h, diluted with saturated
NH4Cl solution and stirred for an additional 15 min. The two phases
were partitioned and the aqueous phase was extracted with CH2Cl2.
The combined organic extracts were washed with brine and dried
over anhydrous MgSO4. The solvent was evaporated to give a yel-
low oil, which was purified by column chromatography using Hex/
EtOAc (9:1) to give 8 as a colorless oil (5.4 g, 60%): IR (neat) nmax
4.2.4. 20,40,5,7-Tetramethoxymethoxyisoflavone (10). To a solution of
3-iodochromone 5 (1.20 g, 3.06 mmol) in 1:1 DME/H2O (50 mL)
were added 10% Pd/C (0.160 g, 5 mol %), Na2CO3 (0.970 g,
9.18 mmol) and phenylboronic acid 6 (1.11 g, 4.59 mmol). The
resulting mixture was stirred at 40e45 ꢂC overnight. The catalyst
was filtered and washed with water and EtOAc. The aqueous phase
was extracted with EtOAc, and the combined organic layers were
washed with water, brine and dried over anhydrous MgSO4. The
solvent was evaporated and the crude product was purified by silica
gel column chromatography using Hex/EtOAc (7:3) to afford an
isoflavone 10 (1.1 g, 78%) as a yellow oil: IR (neat) nmax 2905, 2828,
1647, 1609, 1570, 1256, 1150, 999, 918 cmꢁ1 1H NMR (CDCl3,
;
400 MHz)
d
7.75 (1H, s, H-2), 7.22 (1H, d, J¼8.5 Hz, H-60), 6.88 (1H, d,
2955, 2902, 2827, 1768, 1591, 1487, 1219, 1138, 1004, 772 cmꢁ1
NMR (CDCl3, 400 MHz)
;
1H
J¼2.3 Hz, H-30), 6.76e6.72 (3H, m, H-6, H-8, H-50), 5.27 (2H, s,
OCH2O), 5.23 (2H, s, OCH2O), 5.17 (2H, s, OCH2O), 5.10 (2H, s,
OCH2O), 3.52 (3H, s, OCH3), 3.50 (3H, s, OCH3), 3.47 (3H, s, OCH3),
d
7.19 (1H, t, J¼8.3 Hz, H-5), 6.75 (1H, t,
J¼2.3 Hz, H-2), 6.71 (2H, dd, J¼2.3 and 8.3 Hz, H-4 and H-6), 5.16
(4H, s, 2ꢀ OCH2O), 3.48 (6H, s, 2ꢀ OCH3); 13C NMR (CDCl3,
3.41 (3H, s, OCH3); 13C NMR (CDCl3, 100 MHz)
d 174.9 (C, C-4), 160.9
100 MHz)
d
158.3 (2ꢀ C, C-1 and C-3), 129.9 (CH, C-5), 109.6 (2ꢀ CH,
(C, C-7), 159.4 (C, C-8a), 158.5 (C, C-5), 158.4 (C, C-40), 156.2 (C, C-20),
151.8 (CH, C-2), 132.4 (CH, C-60), 123.1 (C, C-3), 115.5 (C, C-10), 111.5
(C, C-4a), 108.9 (CH, C-50), 104.1 (CH, C-30), 102.4 (CH, C-6), 97.3 (CH,
C-8), 95.8 (CH2, OCH2O), 95.1 (CH2, OCH2O), 94.5 (CH2, OCH2O), 94.3
(CH2, OCH2O), 56.5 (CH3, OCH3), 56.4 (CH3, OCH3), 56.1 (CH3, OCH3),
56.0 (CH3, OCH3); HRMS-ESI m/z [MþNa]þ calcd for C23H26NaO10
485.1424, found 485.1415.
C-4 and C-6), 105.0 (CH, C-2), 94.5 (2ꢀ OCH2O), 55.9 (2ꢀ OCH3);
LRMS-ESI m/z [M]þ 198.1.
4.2.2. 1-Iodo-2,4-dimethoxymethoxybenzene (9). CH3CO2Ag (5.10 g,
30.3 mmol) was added to a solution of 8 (5.00 g, 25.2 mmol) in
CHCl3 (50 mL). The mixture was stirred for 5 min, and then a so-
lution of I2 (7.04 g, 27.7 mmol) in CHCl3 (150 mL) was added
dropwise to the stirred suspension. The resulting mixture was
stirred at rt for 5 h and filtered to remove the AgI. The filtrate was
washed with 10% Na2S2O3 solution, 5% NaHCO3 solution, H2O and
brine. The organic phase was dried over anhydrous MgSO4 and the
solvent evaporated to give a colourless oil. The oil was purified by
flash chromatography using Hex/EtOAc (9:1) to afford the iodin-
ated compound 9 as a colorless oil (7.76 g, 95%): IR (neat) nmax
2956, 2902, 2826, 1716, 1577, 1567, 1474, 1219, 1149, 982,
4.2.5. 20,40,5,7-Tetrahydroxyisoflavone (4)25,26. HCl (3 M, 15 mL)
was added to a solution of 10 (1.00 g, 2.16 mmol) in CH3OH
(30 mL) and stirred at 50 ꢂC for 12 h. CH3OH was evaporated and
the reaction mixture was extracted with EtOAc. The combined
organic phases were washed with H2O and brine. The organic
layer was dried over anhydrous MgSO4 and the solvent evaporated
under reduced pressure to give a yellow solid. Purification of the
solid by column chromatography using Hex/EtOAc (1:1) afforded 4
as a pale yellow solid (0.45 g, 73%): recrystallization of 4 from Hex/
EtOAc (1:4) gave pale yellow needles. Mp 268.4e270.1 ꢂC (lit.26
mp 272.0 ꢂC); IR (neat) nmax 3319, 1652, 1613, 1502, 1254,
772 cmꢁ1; 1H NMR (CDCl3, 400 MHz)
d
7.62 (1H, d, J¼8.5 Hz, H-6),
6.80 (1H, d, J¼2.5 Hz, H-3), 6.53 (1H, dd, J¼2.5 and 8.5 Hz, H-5),
5.21 (2H, s, OCH2O), 5.13 (2H, s, OCH2O), 3.50 (3H, s, OCH3), 3.46
(3H, s, OCH3); 13C NMR (CDCl3, 100 MHz)
d
158.7 (C, C-4), 156.7 (C,
1171 cmꢁ1 1H NMR (CD3OD, 400 MHz)
; d 8.00 (1H, s, H-2), 7.04
C-2), 139.2 (CH, C-6), 111.4 (CH, C-5), 104.4 (CH, C-3), 95.0 (CH2,
OCH2O), 94.5 (CH2, OCH2O), 77.4 (C, C-1), 56.4 (CH3, OCH3), 56.0
(CH3, OCH3); HRMS-ESI m/z [MþNa]þ calcd for C10H13INaO4
346.9756, found 346.9754.
(1H, d, J¼8.2 Hz, H-60), 6.40 (1H, d, J¼2.3 Hz, H-30), 6.37 (1H, dd,
J¼2.3 and 8.2 Hz, H-50), 6.36 (1H, d, J¼2.3 Hz, H-8), 6.23 (1H, d,
J¼2.3 Hz, H-6); 13C NMR (CD3OD, 100 MHz)
d 182.7 (C, C-4), 166.2
(C, C-7), 163.7 (C, C-5), 160.2 (C, C-40), 159.8 (C, C-8a), 157.8 (C, C-
20), 156.7 (CH, C-2), 133.2 (CH, C-60), 122.6 (C, C-3), 110.9 (C, C-10),
108.2 (CH, C-50), 106.2 (C, C-4a), 104.4 (CH, C-30), 100.3 (CH, C-6),
94.9 (CH, C-8), HRMS-ESI m/z [MꢁH]ꢁ calcd for C15H9O6 285.0399,
found 285.0399.
4.2.3. 2,4-Dimethoxymethoxyphenylboronic acid (6)27. Triisopropyl
borate (10.7 mL, 46.3 mmol) was added to the stirred solution of
aryl iodide 9 (5.00 g, 15.4 mmol) in THF/Et2O (1:2, 100 mL) under
N2. The solution was cooled to ꢁ100 ꢂC using liquid N2 and CH3OH
bath, and then n-BuLi (14.5 mL of a 1.6 M solution in hexanes,
23.2 mmol) was added slowly with stirring. After 1 h of stirring at
the temperature below ꢁ78 ꢂC, saturated NH4Cl solution was
added. The solution was stirred for an additional 1 h at rt and the
two phases partitioned. The aqueous phase was extracted with
Et2O. The combined organic phases were washed with H2O and
brine, and dried over anhydrous MgSO4. The solvent was evapo-
rated under reduced pressure to give an orange oil. Purification of
the oil by column chromatography (8:2 Hex/EtOAc) and
4.2.6. Lupinalbin A (3)23. DDQ (79.0 mg, 0.349 mmol) was added
under N2 to a solution of 4 (100 mg, 0.35 mmol) in THF (20 mL). The
reaction mixture was heated to 60 ꢂC with stirring for 15 min.
Additional DDQ (79.0 mg, 0.349 mmol) was added to the mixture
and stirring was continued at the same temperature for 30 min. The
solvent was evaporated and the crude mixture purified by column
chromatography using Hex/EtOAc as eluent to give coumar-
onochromone 3 (66 mg, 66%) as a white solid: 3 was recrystallized
from Hex/EtOAc (1:4) to afford white needle-like crystals, which

8658
M.A. Selepe et al. / Tetrahedron 67 (2011) 8654e8658
decomposed at 278.4e280.0 ꢂC (lit.14 mp >300 ꢂC); IR (neat) nmax
Supplementary data associated with this article can be found, in the
online version, at doi:10.1016/j.tet.2011.09.042.
3327, 3101, 2922, 1622, 1436, 1029, 822 cmꢁ1 1H NMR (CD3OD,
;
400 MHz)
d
7.75 (1H, d, J¼8.4 Hz, H-60), 6.99 (1H, d, J¼1.9 Hz, H-30),
6.89 (1H, dd, J¼1.9 and 8.4 Hz, H-50), 6.46 (1H, d, J¼2.0 Hz, H-8),
References and notes
6.27 (1H, d, J¼2.0 Hz, H-6); 13C NMR (CD3OD, 100 MHz)
d 180.0 (C,
C-4),166.2 (C, C-2),165.2 (C, C-7),164.0 (C, C-5),157.8 (C, C-40),156.6
(C, C-8a),151.9 (C, C-20),122.5 (CH, C-60), 115.2 (CH, C-50), 114.7 (C, C-
10), 104.5 (C, C-4a), 100.9 (CH, C-6), 99.5 (C, C-3), 98.7 (CH, C-30),
95.8 (CH, C-8); HRMS-ESI m/z [MꢁH]ꢁ calcd for C15H7O6 283.0243,
found 283.0239.
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We are grateful to the National Research Foundation (South
Africa) and the University of Kwazulu-Natal for financial assistance.
Supplementary data
Copies of 1H and 13C NMR spectra of 8, 9, 6, 10, 4, 3 and lupi-
nalbin H (2) as well as copies of HSQC and HMBC NMR spectra of 2.
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