Efficient Total Synthesis of (±)-Isoguaiacin and (±)-Isogalbulin

Article abstract of DOI:10.1055/s-0036-1588788

1-Arylnaphthalene lignans such as (-)-isoguaiacin and (-)-isogalbulin have been reported to exhibit notable biological properties. While (-)-isoguaiacin has not been previously synthesized, syntheses of (-)-isogalbulin are generally long and produce a mixture of stereoisomers. We herein present the efficient total synthesis of (±)-isoguaiacin and (±)-isogalbulin in seven and eight steps with an overall yield of 46% and 36%, respectively. The reported approach harnesses a hydrogenolysis reaction in acidic conditions, to convert a furan into an arylnaphthalen structure.

Full text of DOI:10.1055/s-0036-1588788

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2017, 28, A–D
letter
A
de
L. I. Pilkington et al.
Letter
Synlett
Efficient Total Synthesis of (±)-Isoguaiacin and (±)-Isogalbulin
Lisa I. Pilkington
Soo Min Song
Bruno Fedrizzi
MeO
MeO
O
MeO
MeI
HO
David Barker*
0
0
0
0
0-
0
0
2
3-
4
2
5
6-
5
5
2
HO
OMe
OMe
School of Chemical Sciences, University of Auckland,
Private Bag 92019, Auckland 1142, New Zealand
d.barker@auckland.ac.nz
OMe
OMe
OH
vanillin
(
)-isoguaiacin
(
)-isogalbulin
7 steps (46% overall)
from vanillin
8 steps (36% overall)
from vanillin
Received: 06.03.2017
Accepted after revision: 21.03.2017
Published online: 19.04.2017
(–)-isoguaiacin (1) specifically has been shown to exhibit
antioxidant,5 hepaprotective,5 neuroprotective,6 antiprolif-
erative,7,9 and increased osteoblast differentiation.8 (–)-Isogal-
bulin (2) has been isolated from Virola sebifera10 and has not
been shown to exhibit such a wide range activities, but has
demonstrated an increase in osteoblast differentiation.8 Lig-
nans (–)-1 and (–)-2 have the less common 8,8′-syn stereo-
chemistry; compounds with a trans relationship have been
more commonly found and synthesised.
While the synthesis of (±)-isoguaiacin (1) has not been
previously reported, (+)-2 has previously been synthesised.
Some of these syntheses involve the conversion of other
natural products4,11,12 and typically provide aryltetralins in
low overall yields and as mixtures of stereoisomers.13,14
Whitby et al. reported the synthesis of (±)-2 using zirconi-
um chemistry in 21% overall yield,15 and Wang et al. suc-
cessfully produced (±)-2, albeit in a lengthy, nonselective
synthesis of 12 steps,16 while the first enantioselective syn-
theses of (+)-2 was reported by Xie et al., in 10 steps utilis-
ing a Sharpless epoxidation as the enantiodetermining
step.17
During the course of our investigation into the synthesis
of various lignans,18–32 we have noted various rearrange-
ment reactions, particularly in the synthesis of tetrahydro-
furan natural products. To further explore the possibility of
stereoselectively synthesising the 1-arylnaphthalene natu-
ral product scaffold through the hydrogenation of furanoid
compounds,33,34 we attempted to explore an efficient, selec-
tive synthetic route to both (±)-1 and (±)-2.
We envisioned one of the pivotal transformations in the
synthesis of aryl tetralins would be the conversion of a fu-
ran structure, which could be synthesised through a Paal–
Knorr synthesis of the corresponding diketone (Figure 2).
The diketone structure itself could be formed from the di-
merisation of related, substituted benzaldehyde derivatives.
Owing to their aforementioned promising biological prop-
DOI: 10.1055/s-0036-1588788; Art ID: st-2017-d0162-l
Abstract 1-Arylnaphthalene lignans such as (–)-isoguaiacin and (–)-
isogalbulin have been reported to exhibit notable biological properties.
While (–)-isoguaiacin has not been previously synthesized, syntheses of
(–)-isogalbulin are generally long and produce a mixture of stereoiso-
mers. We herein present the efficient total synthesis of (±)-isoguaiacin
and (±)-isogalbulin in seven and eight steps with an overall yield of 46%
and 36%, respectively. The reported approach harnesses a hydrogenoly-
sis reaction in acidic conditions, to convert a furan into an arylnaphtha-
len structure.
Key words lignan, 1-arylnaphthalene, synthesis, Paal–Knorr, cycliza-
tion
1-Arylnaphthalene (aryl tetralin) lignan natural prod-
ucts, including (–)-isoguaiacin (1) and (–)-isogalbulin (2,
Figure 1), have received considerable attention owing to
their notable and varied biological properties. 1-Arylnaph-
thalene lignans have been shown to possess antitumour
and anti-HIV activities,1 as well as indications of activity
against Parkinson’s and Alzheimer’s disease, along with nu-
merous others.2
First isolated in 1964 from Guaiacum officinale3 and
since then from a range of natural sources including Larrea
tridentate,4 Machilus thunbergii,5–8 Calyptranthes pallens,9
7
9
MeO
HO
MeO
MeO
8
8'
9'
7'
OMe
OMe
(–)-isoguaiacin (1)
(–)-isogalbulin (2)
OH
OMe
Figure 1 Structures of 8,8′-syn-1-arylnaphthalen lignan natural prod-
ucts.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

B
L. I. Pilkington et al.
Letter
Synlett
erties and to synthesise (±)-1 for the first time and improve
the efficiency of the synthesis of (±)-2, we identified (±)-
isoguaiacin (1) as our primary synthetic target, which could
then be methylated to provide (±)-isogalbulin (2).
O
O
BnBr, K2CO3
acetone, reflux
H
H
84%
HO
BnO
4
3
OMe
OMe
3.0 M EtMgBr
toluene, 0 °C
R
O
furan
74%
R
R
OH
O
Paal–Knorr
synthesis
CrO3, pyridine
CH2Cl2, r.t.
R
H
aryl tetralin
O
quant.
BnO
BnO
(
)-5
6
OMe
OMe
OMe
O
O
R
R
BnO
Br2, CHCl3
92%
substituted
benzaldehyde
R
diketone
Figure 2 Retrosynthetic analysis towards 8,8′-syn-1-arylnaphthalenes
O
(
i) Na, NH3
FeCl3, THF
–78 °C
O
O
Br
)-7
ii) 6, THF
80%
BnO
As we envisioned the key transformation to involve a
catalytic hydrogenation reaction, we decided that a benzyl
moiety would be an appropriate protecting group for the
phenols in 1, thus vanillin (3) was benzyl-protected to give
benzaldehyde 4 in 84% yield (Scheme 1).35 In order to ex-
tend the carbon chain by two carbon atoms, EtMgBr was
added to benzaldehyde 4 to provide alcohol 5 which was
then oxidised in quantitative yield to ketone 6 following
Collins oxidation procedures.35 With the successful prepa-
ration of ketone 6, one of the two intermediates required
for the dimerisation reaction, the next step was bromina-
tion of 6 to produce the other key intermediate 7. Following
procedures by Adler et al., 6 was brominated using Br2 in
CHCl3 at room temperature, giving bromoketone 7 in 92%
yield.36
OMe
OBn
OMe
(
)-8
HCl in MeOH
CH2Cl2, reflux
quant.
p-TSA, Pd/C
THF, AcOH, H2
quant.
(
)-1
O
BnO
OBn
9
MeI, K2CO3
acetone, 40 °C
78%
MeO
OMe
(
)-2
Scheme 1 Synthesis of (±)-isoguaiacin (1) and (±)-isogalbulin (2)
With ketone 6 and α-bromoketone 7 in hand, 1,4-dike-
tone 8 was synthesised by the reaction of these two units
using methodology reported by Perry et al. and Schneiders
and Stevenson.37,38 That is, the treatment of ketone 6 with
sodamide, prepared by the mixing of ferric chloride and so-
dium metal in liquid ammonia at –78 °C, followed by the
addition of α-bromoketone 7 to the reaction mixture. Once
synthesised, 1,4-diketone 839 was then converted into
quantitative yield to the furan 9 by treatment with HCl. Fi-
nally, furan 940 was hydrogenated, catalysed by Pd/C in the
presence of p-toluenesulfonic acid monohydrate in
THF/AcOH;41 pleasingly, a reaction time of 15 hours provid-
ed the desired product (±)-isoguaiacin (1) in quantitative
yield.42 The NMR data of synthetic 1 was identical to report-
ed values.
ing and resultant formation of a quinone methide 12 which
then undergoes attack by water to give dihydroxyl species
13. Further hydrogenolysis, leads to intermediate 14 which
undergoes elimination of water to give quinone methide 15.
Intramolecular cyclisation of 15 gives 16, which rearoma-
tises to give aryl tetralin, (±)-1.44
Once synthesised, (±)-isoguaiacin (1) was then methyl-
ated using methyl iodide in acetone to give (±)-isogalbulin
(2) in 78% yield, which was again spectroscopically identi-
cal to reported data.45
Overall, (±)-isoguaiacin (1) and (±)-isogalbulin (2) were
synthesised over 7 steps and 8 steps in 46% and 36% yields,
respectively, presenting this as an efficient, high-yielding,
and convenient method to generate these naturally occur-
ring aryl tetralin natural products and associated products.
These methods provide an easy synthesis of these natural
products allowing greater biological investigation without
relying on natural sources.
We hypothesise that (±)-isoguaiacin (1) is formed ac-
cording to the mechanism shown (Scheme 2). Following the
benzyl deprotection of 9, the formed furan 1043 then under-
goes selective hydrogenation to tetrahydrofuran 11 with all
syn stereochemistry. Electron donation from the para hy-
droxy group, in the acidic conditions, allows for ring open-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

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L. I. Pilkington et al.
Letter
Synlett
(9) Lobo-Echeverri, T.; Rivero-Cruz, J. F.; Su, B.-N.; Chai, H.-B.;
Cordell, G. A.; Pezzuto, J. M.; Swanson, S. M.; Soejarto, D. D.;
Kinghorn, A. D. J. Nat. Prod. 2005, 68, 577.
(10) Lopes, L. M. X.; Yoshida, M.; Gottlieb, O. R. Phytochemistry 1984,
23, 2647.
H2
O
O
HO
OH
HO
OH
H
MeO
OMe
MeO
OMe
10
11
(11) Messiano, G. B.; Wijeratne, E. M. K.; Lopes, L. M. X.; Gunatilaka,
A. A. L. J. Nat. Prod. 2010, 73, 1933.
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1987, 28, 5161.
(13) Perry, C. W.; Kalmins, M. V.; Deitcher, K. H. J. Org. Chem. 1972,
37, 4371.
H
HO
OHHO
OMe MeO
O
OH
OH
O
(14) Landais, Y.; Robin, J.-P.; Lebrun, A.; Lenain, V. Tetrahedron Lett.
1987, 28, 5161.
(15) Kastatkin, A. N.; Checksfield, G.; Whitby, R. J. J. Org. Chem. 2000,
65, 3236.
MeO
OMe
H
H
O
12
13
H
H
H2
H+
– H2O
(16) Peng, Y.; Luo, Z.-B.; Zhang, J.-J.; Luo, L.; Wang, Y.-W. Org. Biomol.
Chem. 2013, 11, 7574.
(17) Li, X.; Jiao, X.; Liu, X.; Tian, C.; Dong, L.; Yao, Y.; Xie, P. Tetrahe-
dron Lett. 2014, 55, 6324.
(18) Pilkington, L. I.; Barker, D. J. Org. Chem. 2012, 77, 8156.
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(20) Pilkington, L. I.; Wagoner, J.; Polyak, S. J.; Barker, D. Org. Lett.
2015, 17, 1046.
MeO
HO
MeO
HO
OH
OMe
OH2
OMe
15
14
OH
(21) Jung, E.; Pilkington, L. I.; Barker, D. J. Org. Chem. 2016, 81, 12012.
(22) Jung, E.; Dittrich, N.; Pilkington, L. I.; Rye, C. E.; Leung, E.; Barker,
D. Tetrahedron 2015, 71, 9439.
(23) Rye, C.; Barker, D. Synlett 2009, 3315.
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2012, 84, 1557.
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4464.
(26) Duhamel, N.; Rye, C. E.; Barker, D. Asian J. Org. Chem. 2013, 2,
491.
MeO
MeO
HO
HO
– H+
H
16
(
)-isoguaiacin 1
OMe
OMe
OH
OH
(27) Paterson, D. L.; Barker, D. Beilstein J. Org. Chem. 2015, 11, 265.
(28) Davidson, S. J.; Barker, D. Tetrahedron Lett. 2015, 56, 4549.
(29) Pilkington, L. I.; Barker, D. Synlett 2015, 26, 2425.
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(31) Tran, H.; Dickson, B.; Barker, D. Tetrahedron Lett. 2013, 54, 2093.
(32) Rye, C. E.; Barker, D. J. Org. Chem. 2011, 76, 6636.
(33) Crossley, N. S.; Djerassi, C. J. Chem. Soc. 1962, 1459.
(34) Wu, A.; Zhao, Y.; Yang, W.; Wang, M.; Pan, X. Synth. Commun.
1997, 27, 2087.
Scheme 2 Proposed mechanism for the generation of (±)-isoguaiacin
(1)
Acknowledgment
We wish to acknowledge the University of Auckland for funding for
this work.
(35) Kuwano, M.; Ono, M.; Tomita, M.; Watanabe, J.; Takeda, M. WO
9415594A1, 1994.
(36) Adler, E.; Delin, S.; Miksche, G. E. Acta Chem. Scand. 1996, 20,
1035.
(37) Perry, C. W.; Kalnis, M. V.; Deitcher, K. H. J. Org. Chem. 1972, 37,
4371.
References and Notes
(1) Ayres, D. C.; Loike, J. D. Lignans: Chemical, Biological and Clinical
Properties; 1990.
(2) Ma, C. J.; Kim, S. R.; Kim, J.; Kim, Y. C. Br. J. Pharmacol. 2005, 146,
752.
(3) King, F. E.; Wilson, J. G. J. Chem. Soc. 1964, 4011.
(4) Konno, C.; Lu, Z.-Z.; Xue, H.-Z.; Erdelmeier, C. A. J.; Meksuriyen,
D.; Che, C. T.; Cordell, G. A.; Soejarto, D. D.; Waller, D. P.; Fong, H.
H. S. J. Nat. Prod. 1990, 53, 396.
(5) Yu, Y. U.; Kang, S. K.; Park, H. Y.; Sung, S. H.; Lee, E. J.; Kim, S. Y.;
Kim, Y. C. J. Pharm. Pharmacol. 2000, 52, 1163.
(6) Ma, C. J.; Sung, S. H.; Kim, Y. C. Planta Med. 2004, 70, 79.
(7) Lee, J. S.; Kim, J.; Yu, Y. U.; Kim, Y. C. Arch. Pharm. Res. 2004, 27,
1043.
(38) Schneiders, G. E.; Stevenson, R. J. Org. Chem. 1981, 46, 2969.
(39) (±)-2′,3′-Bis(4-benzyloxy-3-methoxybenzoyl)butane (8)
To liquid NH3 (20 mL) at –78 °C was added FeCl3 (0.002 g) and
Na (0.092 g, 3.95 mmol) and the mixture stirred for 2.5 h. To the
dark-grey suspension of sodamide was added a solution of 6
(0.464 g, 1.72 mmol) in THF (6 mL), dropwise over 10 min and
stirred for 40 min. A solution of 7 (0.600 g, 1.72 mmol) in THF
(18 mL) was then added dropwise over 30 min. After the
mixture was stirred for a further 2.5 h, NH4Cl (0.500 g) was
added, and the mixture warmed to r.t. to remove the NH3. The
mixture was then filtered, washed with EtOAc, and concen-
trated in vacuo to give the crude product which was then puri-
fied using flash chromatography (9:1 n-hexanes–EtOAc) to give
the title product (0.742 g, 80%) as a colorless semisolid. 1H NMR
(400 MHz, CDCl3): δ = 1.27 (6 H, d, J = 6.6 Hz, 2′-CH3 and 3′-CH3),
(8) Lee, M. K.; Yang, H.; Ma, C. J.; Kim, Y. C. Biol. Pharm. Bull. 2007,
30, 814.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

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L. I. Pilkington et al.
Letter
Synlett
3.87–3.96 (8 H, m, 2 × OCH3, H-2′ and H-3′), 5.23 (4 H, s, 2 ×
ArCH2), 6.91 (2 H, d, J = 8.4 Hz, H-5, H-5′′′), 7.31 (2 H, tt, J = 1.2,
7.2 Hz, H-4, H-4′′′), 7.35–7.40 (4 H, m, H-3′′, H-5′′, H-3′′′′, H-5′′′′),
7.42–7.44 (4 H, m, H-2′′, H-6′′, H-2′′′′, H-6′′′′), 7.50 (2 H, d, J = 2.0
Hz, H-2, H-2′′′), 7.61 (2 H, dd, J = 2.0, 8.4 Hz, H-6, H-6′′′). 13C
NMR (100 MHz, CDCl3): δ = 16.0 (2′-CH3 and 3′-CH3), 43.3 (C-2′
and C-3′), 56.0 (2 × OCH3), 70.8 (2 × OCH2), 111.2 (C-2 and C-
2′′′), 112.3 (C-5 and C-5′′′), 122.9 (C-6 and C-6′′′), 127.2 (C-2′′, C-
6′′, C-2′′′′ and C-6′′′′), 128.1 (C-4′′ and C-4′′′′), 128.7 (C-3′′, C-5′′,
C-3′′′′, and C-5′′′′), 129.5 (C-1 and C-1′′′), 136.4 (C-1′′, C-1′′′′),
149.5 (C-3 and C-3′′′), 152.4 (C-4 and C-4′′′), 203.0 (C-1′ and C-
4′). The 1H NMR and 13C NMR data were consistent with those
reported in literature.46
brown solid; mp 147–149 °C (lit. 149 °C). 1H NMR (400 MHz,
CDCl3): δ = 0.89–0.90 (6 H, m, H-9 and H-9′), 1.92–1.95 (1 H, m,
H-8′), 2.02–2.04 (1 H, m, H-8), 2.46 (1 H, dd, J = 7.2, 16.0 Hz, H-
7b), 2.90 (1 H, dd, J = 5.6, 16.0 Hz, H-7a), 3.59 (1 H, d, J = 6.4 Hz,
H-7′), 3.81 (3 H, s, OCH3), 3.86 (3 H, s, OCH3), 5.35 (br s, OH),
5.47 (br s, OH), 6.41 (1 H, s, H-5), 6.49 (1 H, dd, J = 2.0, 8.1 Hz, H-
6′), 6.55 (1 H, d, J = 2.0 Hz, H-2′), 6.57 (1 H, s, H-2), 6.78 (1 H, d,
J = 8.1 Hz, H-5′). 13C NMR (100 MHz, CDCl3): δ = 15.8 and 15.9
(C-9 and C-9′), 29.3 (C-8), 35.3 (C-7), 40.6 (C-8′), 50.5 (C-7′),
55.9 (3-OCH3 and 3′-OCH3), 110.6 (C-2), 111.5 (C-2′), 113.8 (C-
5′), 116.1 (C-5), 122.0 (C-6′), 127.6 (C-6), 130.9 (C-1), 139.0 (C-
1′), 143.5 (C-4), 143.7 (C-4′), 145.0 (C-3), 146.2 (C-3′). The 1H
NMR and 13C NMR data were consistent with that reported in
literature.44
(40) 3,4-Dimethyl-2,5-bis(4′-benzyloxy-3′-methylphenyl)furan
(9)
(43) Hydrogenation of 9 for one hour leads to complete removal of
the benzyl groups to give 10 only; an extended reaction time is
required to transform 10 into (±)-1.
(44) Wang, B.-G.; Hong, X.; Li, L.; Zhou, J.; Hhao, X.-J. Planta Med.
2000, 66, 511.
To a solution of diketone 8 (0.300 g, 0.557 mmol) in CH2Cl2 (5.5
mL) was added a solution of aq methanolic HCl (9.45 mL, 4.8%
HCl in MeOH) and stirred at 80 °C at reflux for 2.75 h. The
mixture was then cooled to r.t. to give the title product (0.29 g,
quant.) as a white solid; mp 155 °C. 1H NMR (400 MHz, CDCl3):
δ = 2.20 (6 H, s, 3-CH3 and 4-CH3), 3.95 (6 H, m, 2 × OCH3), 5.20
(4 H, s, 2 × ArCH2), 6.94 (2 H, d, J = 8.4 Hz, H-5, H-5′′′), 7.14 (2 H,
dd, J = 1.6, 8.4 Hz, H-6′, H-6′′′), 7.24 (2 H, d, J = 1.6 Hz, H-2′, H-
2′′′), 7.31 (2 H, t, J = 7.2 Hz, H-4′′, H-4′′′′), 7.38 (4 H, t, J = 7.2 Hz,
H-3′′, H-5′′, H-3′′′′, H-5′′′′), 7.46 (4 H, d, J = 7.2 Hz, H-2′′, H-6′′, H-
2′′′′, H-6′′′′). 13C NMR (100 MHz, CDCl3): δ = 9.9 (3-CH3 and 4-
CH3), 56.1 (2 × OCH3), 71.2 (2 × OCH2), 109.8 (C-2 and C-2′′′),
114.2 (C-5 and C-5′′′), 118.1 (C-3 and C-4), 118.4 (C-6′ and C-
6′′′), 125.7 (C-1 and C-1′′′), 127.3 (C-2′′, C-6′′, C-2′′′′, and C-6′′′′),
127.9 (C-4′′ and C-4′′′′), 128.6 (C-3′′, C-5′′, C-3′′′′, and C-5′′′′),
137.2 (C-1′′ and C-1′′′′), 146.9 (C-2 and C-5), 147.2 (C-4′ and C-
4′′′′), 149.7 (C-3′, C-3′′′).
(45) (±)-Isogalbulin (2)
To a stirred solution of 1 (0.025 g, 0.076 mmol) in acetone (3
mL) was added K2CO3 (0.053 g, 0.38 mmol), followed by MeI
(0.024 mL, 0.38 mmol) and the mixture stirred at 40 °C for 3 d.
The reaction mixture was then filtered and the to give the title
product (0.0205 g, 78%) as a colorless oil. 1H NMR (400 MHz,
CDCl3): δ = 0.90–0.93 (6 H, m, H-9 and H-9′), 1.92–1.96 (1 H, m,
H-8′), 2.00–2.05 (1 H, m, H-8), 2.46 (1 H, dd, J = 8.0, 16.0 Hz, H-
7b), 2.87 (1 H, dd, J = 5.6, 16.0 Hz, H-7a), 3.67 (3 H, s, OCH3),
3.67–3.69 (1 H, m, H-7′), 3.80 (3 H, s, OCH3), 3.86 (3 H, s, OCH3),
3.87 (3 H, s, OCH3), 6.35 (1 H, s, H-5), 6.50 (1 H, dd, J = 2.0, 8.0
Hz, H-6′), 6.57 (1 H, d, J = 2.0 Hz, H-2′), 6.60 (1 H, s, H-2), 6.74 (1
H, d, J = 8.0 Hz, H-5′). 13C NMR (100 MHz, CDCl3): δ = 16.2 and
16.5 (C-9 and C-9′), 28.6 (C-8), 34.7 (C-7), 40.8 (C-8′), 50.9 (C-
7′), 55.69 (OCH3), 55.74 (OCH3), 55.78 (OCH3), 55.83 (OCH3),
110.6 (C-5′), 111.0 (C-2), 112.2 (C-2′), 113.3 (C-5), 121.3 (C-6′),
128.4 (C-6), 129.5 (C-1), 139.8 (C-1′), 147.1 and 147.2 (C-3, C-4,
(41) Stevenson, R.; Williams, J. R. Org. Prep. Proc. Int. 1976, 8, 179.
(42) (±)-Isoguaiacin (1)
To furan 9 (0.100 g, 0.192 mmol) in a solution of THF (5.5 mL)
and AcOH (2.3 mL) was added p-toluenesulfonic acid monohy-
drate (0.010 g, 10 % w/w) and Pd/C (0.100 g, 100 % w/w). The
mixture was stirred under and atmosphere of hydrogen for 15 h
and was then filtered through Celite. To the filtrate was added
water (4 mL), and the mixture was extracted with water (2 mL),
followed by brine (2 mL), dried (MgSO4), and concentrated in
vacuo to afford the title product (0.065 g, quant.) as an orange-
1
C-4′), 148.6 (C-3′). The H NMR and 13C NMR data were consis-
tent with those reported in literature.17
(46) Yamauchi, S.; Masuda, T.; Sugahara, T.; Kawaguchi, Y.; Ohuchi,
M.; Someya, T.; Akiyama, J.; Tominaga, S.; Yamawaki, M.;
Kishida, T.; Akiyama, K.; Maruyuma, M. Biosci. Biotechnol. Bio-
chem. 2008, 72, 2981.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D