Stereoselective total synthesis of rhoiptelol B via prins cyclization

Article abstract of DOI:10.1055/s-0033-1340181

The stereoselective total synthesis of rhoiptelol B, a diaryl? heptanoid isolated from Rhoiptelea chiliantha is described. The tetrahydropyran ring was constructed by using Prins cyclization. The key steps involved in this synthesis are Prins cyclization,

Full text of DOI:10.1055/s-0033-1340181

LETTER
▌661
lSettteer reoselective Total Synthesis of Rhoiptelol B via Prins Cyclization
Stereoselective Total Synthesis of Rhoiptelol B
Jhillu S. Yadav,*a,b Md. Ataur Rahman,a N. Mallikarjuna Reddy,a Attaluri R. Prasad,a Ahmad Al Khazim Al Ghamdib
a
Centre for Semio Chemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160512; E-mail: yadavpub@gmail.com
b
Engineer Abdullah Bagshan for Bee Research, King Saud University, Saudi Arabia
Received: 17.12.2013; Accepted after revision: 10.01.2014
we have undertaken the total synthesis of rhoiptelol B
Abstract: The stereoselective total synthesis of rhoiptelol B, a diaryl-
(Figure 1).8
heptanoid isolated from Rhoiptelea chiliantha is described. The tet-
rahydropyran ring was constructed by using Prins cyclization. The
key steps involved in this synthesis are Prins cyclization, Mistunobu
OH
inversion, cross metathesis, Sharpless asymmetric dihydroxylation,
and hydrogenolysis.
Key words: rhoiptelol B, natural products, diarylheptanoid, Prins
O
cyclization, Mitsunobu inversion
OH
HO
OH
OMe
rhoiptelol B (1)
The plant metabolites known as diarylheptanoids, isolated
from various sources,1 contain a 1,7-diphenylheptane
skeleton. Due to the special structural features of diaryl-
heptanoids, they have different biological activities2,3
such as antioxidant, anti-inflammatory, antitumor, neuro-
protective, heptoprotective, anticancer, antialergic, cho-
lesterol-lowering effect, and anti-HIV activities. The
compound rhoiptelol B4,5 is one of the families of diaryl-
heptanoids containing a tetrahydropyran ring, isolated
form fruits of Rhoiptelea chiliantha and also form bark of
Anlus hirsute in 1996 and 2007, respectively. It has shown
inhibitory activities against LPS-induced NF-KB activa-
tion, NO, and TNF-α, production, and HIF-1 in AGS
cells.5 In our ongoing program on the utilization of the
highly stereoselective Prins cyclization reaction, a well-
established method for constructing multisubstituted
tetrahydropyrans6 for the synthesis of polyketide motifs,7
Figure 1 Structure of rhoiptelol B (1)
The retrosynthetic analysis of rhoiptelol B is described in
Scheme 1. It could be achieved from hydrogenolysis of
cyclic carbonate of diol 2, which in turn was obtained
from cross metathesis of the olefins 3 and 4 followed by
Sharpless asymmetric dihydroxylation. The tetrahydropy-
ran moiety 3 was constructed via Prins cyclization be-
tween isovalinal (5) and homoallylic alcohol 6.
Our synthesis of rhoiptelol B is outlined in Scheme 2.
Prins cyclization7 between known homoallylic alcohol 69
and isovalinal (5) in the presence of TFA resulted in the
trifluoroacetate salt of 7, which on treatment with K2CO3
in MeOH gave tetrahydropyran diol 7 as the only isolable
diastereomer in 62% yield. Inversion of the secondary hy-
droxyl group using Mitsunobu’s protocol10 produced in-
OH
OMOM
OH
O
O
OH
OH
HO
OH
MOMO
OMOM
1
2
OMe
OMe
OMOM
O
+
O
+
HO
HO
OBn
OMOM
OMe
MOMO
OMe
5
6
3
4
Scheme 1 Retrosynthetic analysis of rhoiptelol B (1)
SYNLETT 2014, 25, 0661–0664
Advanced online publication: 11.02.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1340181; Art ID: ST-2013-B1111-L
© Georg Thieme Verlag Stuttgart · New York

662
J. S. Yadav et al.
LETTER
OH
O
O
a
+
OBn
OBn
HO
HO
OBn
OMe
HO
6
7
5
OMe
OMe
OMOM
OH
O
c
b
O
OBn
9
MOMO
8
HO
OMe
OMOM
OMOM
e
d
O
O
OH
10
MOMO
MOMO
3
OMe
OMe
OMOM
f
O
OMOM
4
MOMO
11
OMOM
OMe
Scheme 2 Reagents and conditions: (a) TFA, CH2Cl2 then K2CO3, MeOH, r.t., 4 h, 62%; (b) DEAD, TPP, 4-C6H4(NO2)COOH, THF, 30 min,
0 °C to r.t. then K2CO3, MeOH, r.t, 1 h, 75%; (c) MOMCl, DIPEA, DMAP, CH2Cl2, 0 °C to r.t., 4 h, 87%; (d) Li/naphthalene, THF, –20 °C,
92%; (e) i) TPP, I2, imidazole, THF, 0 °C to r.t., 4 h; ii) t-BuOK, THF, 0 °C to r.t., 4 h, 76% for two steps; (f) 4, Grubbs II, CH2Cl2, r.t., 6 h, 72%.
versed pyranol 8 in 75% overall yield in two steps.
Protection of both the aromatic and aliphatic hydroxyl
functionality as its MOM ether using DIPEA and MOMCl
in CH2Cl2 produced compound 9 in 87% yield. Removal
of the benzyl group in compound 9 using Li/naphthalene11
in THF resulted pyranyl methanol 10 in 92% yield. Iodin-
ation of primary alcohol of 10 using I2, TPP, and imidaz-
ole in THF followed by elimination with t-BuOK in THF
gave olefin 3 in 76% yield over two steps. The olefin 3
was subjected to cross metathesis with the olefin 415 using
the Grubbs second-generation catalyst in CH2Cl2 and af-
forded compound 11 in 86% yield.
Acknowledgement
N.M.R. thanks CSIR, New Delhi for the award of a fellowship.
J.S.Y. thanks CSIR for the award of a Bhatnagar Fellowship.
References and Notes
(1) Zhu, J.; Islas-Gonzalez, G.; Bois-Choussy, M. Org. Prep.
Proced. Int. 2000, 32, 505.
(2) (a) Joo, S. S.; Kim, S. G.; Choi, S. E.; Kim, Y. B.; Park, H.
Y.; Seo, S. J.; Choi, Y. W.; Lee, M. W.; Lee, D. Eur. J.
Pharmacol. 2009, 614, 98. (b) Lee, C. S.; Jang, E.; Kim, Y.
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2010, 10, 520. (c) Masuda, Y.; Kikuzaki, H.; Hisamoto, M.;
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S. J. Nat. Med. 2008, 62, 374. (e) Han, J. M.; Lee, W. S.;
Kim, J. R.; Son, J.; Nam, K. H.; Choi, S. C.; Lim, J. S.;
Jeong, T. S. J. Agric. Food Chem. 2007, 55, 9457. (f) Ishida,
J.; Kozuka, M.; Tokuda, H.; Nishino, H.; Nagumo, S.; Lee,
K. H.; Nagai, M. Bioorg. Med. Chem. 2002, 10, 3361.
(g) Ishida, J.; Kozuka, M.; Wang, H. K.; Konoshima, T.;
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N.; Lee, K. H.; Nagai, M. Cancer Lett. 2000, 159, 135.
(3) (a) Lee, C. S.; Ko, H. H.; Seo, S. J.; Choi, Y. W.; Lee, M. W.;
Myung, S. C.; Bang, H. Int. Immunopharmacol. 2009, 9,
1097. (b) Ohtsu, H.; Itokawa, H.; Xiao, Z.; Su, C. Y.; Shih,
C. C. Y.; Chiang, T.; Chang, E.; Lee, Y. F.; Chiu, S. Y.;
Chang, C.; Lee, K. H. Bioorg. Med. Chem. 2003, 11, 5083.
(c) Intapad, S.; Suksamrarn, A.; Piyachaturawat, P. Vascul.
Pharmacol. 2009, 51, 284. (d) Winuthayanon, W.; Suksen,
K.; Boonchird, C.; Chuncharunee, A.; Ponglikitmongkol,
The compound 11 on Sharpless asymmetric
dihydroxylation12 using AD-mix-α afforded diol 2 in 92%
yield. The resultant diol was protected as cyclic carbonate
using triphosgene and Et3N in CH2Cl2, followed by hydro-
genolysis which afforded compound 13 in 85% yield for
two steps.13 Finally, removal of MOM ethers using TMS-
Br in CH2Cl2 afforded rhoiptelol B (1) in 72% yield
(Scheme 3).14 The synthetic sample was identical in all re-
spects {1H NMR, 13C NMR, IR, Rf and [α]D} to the natu-
rally isolated compound.4,8
In summary, we described a concise stereoselective total
synthesis of rhoiptelol B via Prins cyclization. Our route
requires total 12 steps from known homoallylic alcohol 6
and provides 11% overall yield.
Synlett 2014, 25, 661–664
© Georg Thieme Verlag Stuttgart · New York

LETTER
Stereoselective Total Synthesis of Rhoiptelol B
663
(8) Previous total synthesis of rhoiptelol B: (a) Yadav, J. S.;
Pandurangam, T.; Bhadra Reddy, V. V.; Reddy, B. V. S.
Synthesis 2010, 4300. (b) Reddy, C. R.; Rao, N. N.;
Srikanth, B. Eur. J. Org. Chem. 2010, 345.
11
a
OMOM
(9) (a) Matsuura, F.; Peters, R.; Anada, M.; Harried, S. S.; Hao,
J.; Kishi, Y. J. Chem. Am. Soc. 2006, 128, 463. (b) Koza, G.;
Theunissen, C.; Al Dulayymi, J. R.; Baird, M. S.
Tetrahedron 2009, 65, 10214. (c) George, S.; Sudalai, A.
Tetrahedron Lett. 2007, 48, 8544.
OH
O
OH
2
MOMO
OMOM
(10) Mitsunobu, O. Synthesis 1981, 1.
b
OMe
(11) Liu, H. J.; Yip, J. Tetrahedron Lett. 1997, 38, 2253.
(12) (a) Carlisle, J.; Fox, D. J.; Warren, S. Chem. Commun. 2003,
2696. (b) Krishna, P. R.; Kumar, E. S. Tetrahedron Lett.
2009, 50, 6676. (c) Sabitha, G.; Nayak, S.; Bhikshapathi,
M.; Yadav, J. S. Tetrahedron Lett. 2009, 50, 5428.
(13) Kobayashi, S.; Matsubara, R.; Nakamura, Y.; Kitagawa, H.;
Sugiura, M. J. Chem. Am. Soc. 2003, 125, 2507.
(14) Imoto, H.; Matsumoto, M.; Odaka, H.; Sakamoto, J.;
Kimura, H.; Nonaka, M.; Kiyota, Y.; Momose, Y. Chem.
Pharm. Bull. 2004, 52, 120.
OMOM
O
O
O
12
MOMO
OMe
O
c
OMOM
(15) Preparation of compound 4 from p-hydroxybenzaldehyde
(Scheme 4).
O
MOMCl, DIPEA, DMAP
CH2Cl2, 0 °C to r.t., 4 h, 86%
OH
O
MOMO
13
OMOM
d
OMe
OMOM
OH
Ph3P=CH2I, t-BuOK, THF
4
0 °C to r.t., 4 h, 82%
OH
Scheme 4
O
(16) (2R,4S,6R)-2-[2-(Benzyloxy)ethyl]-6-(4-hydroxy-3-
methoxyphenyl)tetrahydro-2H-pyran-4-ol (7)
OH
HO
1
OH
[α]D25 +38.3 (c 1.01, CHCl3). 1H NMR (300 MHz, CDCl3):
δ = 7.20–7.17 (m, 5 H), 6.83–6.78 (m, 2 H), 6.77–6.71 (m, 1
H), 5.45 (br s, OH, 1 H), 4.47 (s, 2 H), 4.23 (dd, J = 1.3, 11.3
Hz, 1 H), 3.86 (s, 3 H), 3.70–3.50 (m, 4 H), 2.18–2.08 (m, 1
H), 2.04–1.94 (m, 1 H), 1.93–1.74 (m, 2 H), 1.34–1.20 (m, 2
H). 13C NMR (75 MHz, CDCl3): δ = 146.3, 144.9, 144.94,
138.4, 134.0, 128.3, 127.5, 127.5, 118.9, 114.0, 108.6, 77.1,
OMe
Scheme 3 Reagents and conditions: (a) AD-mix-α, t-BuOH–H2O
(1:1), MeSONH2, 24 h, 0 °C, 92%; (b) triphosgene, Et3N, CH2Cl2; (c)
Raney-Ni, H2, EtOH, 85% for two steps; (d) TMSBr, CH2Cl2, –30 °C,
4 h, 72%.
72.9, 68.4, 66.6, 55.8, 42.5, 40.9, 36.1. IR (neat): νmax
=
3385, 2921, 2853, 1517, 1273, 1074, 1033, 747 cm–1. ESI-
M.; Suksamrarn, A.; Piyachaturawat, P. J. Agric. Food
Chem. 2009, 57, 840.
(4) Jiang, Z.; Jiang, Z.-H.; Tanaka, T.; Hirata, H.; Fukuoka, R.;
Kouno, I. Phytochemistry 1996, 43, 1049.
(5) (a) Jin, W.-Y.; Cai, X. F.; Na, M.-K.; Lee, J. J.; Bae, K.-H.
Arch. Pharmacol. Res. 2007, 30, 412. (b) Jin, W.-Y.; Cai, X.
F.; Na, M.-K.; Lee, J. J.; Bae, K.-H. Biol. Pharm. Bull. 2007,
30, 810.
(6) (a) Barry, C. St. J.; Crosby, S. R.; Harding, J. R.; Hughes, R.
A.; King, C. D.; Parker, G. D.; Willis, C. L. Org. Lett. 2003,
5, 2429. (b) Yang, X.-F.; Mague, J. T.; Li, C.-J. J. Org.
Chem. 2001, 66, 739. (c) Yadav, J. S.; Reddy, B. V. S.;
Sekhar, K. C.; Gunasekar, D. Synthesis 2001, 885.
(d) Yadav, J. S.; Reddy, B. V. S.; Reddy, M. S.; Niranjan, N.
J. Mol. Catal. A: Chem. 2004, 210, 99. (e) Yadav, J. S.;
Reddy, B. V. S.; Reddy, M. S.; Niranjan, N.; Prasad, A. R.
Eur. J. Org. Chem. 2003, 1779. (f) Rychnovsky, S. D.;
Powell, N. A. J. Org. Chem. 1997, 62, 6460.
(7) (a) Yadav, J. S.; Reddy, M. S.; Prasad, A. R. Tetrahedron
Lett. 2005, 46, 2133. (b) Yadav, J. S.; Sridhar Reddy, M.;
Prasad, A. R. Tetrahedron Lett. 2006, 47, 4995. (c) Yadav,
J. S.; Purushothama Rao, P. M.; Sridhar Reddy, M.;
Venkateswar Rao, N.; Prasad, A. R. Tetrahedron Lett. 2007,
48, 1469. (d) Yadav, J. S.; Lakshmi, A. K.; Mallikarjuna
Reddy, N.; Prasad, A. R.; Subba Reddy, B. V. Tetrahedron
2010, 66, 334.
MS: m/z = 381 [M + Na]+.
(2R,4R,6R)-2-[2-(Benzyloxy)ethyl]-6-(4-hydroxy-3-
methoxyphenyl)tetrahydro-2H-pyran-4-ol (8)
[α]D25 +32.2 (c 0.83, CHCl3). 1H NMR (300 MHz, CDCl3):
δ = 7.34–7.29 (m, 5 H), 6.89–6.81 (m, 3 H), 4.77 (d, J = 10.6
Hz, 1 H), 4.51 (s, 2 H), 4.34–4.31 (m, 1 H), 4.17–4.09 (m, 1
H), 3.86 (s, 3 H), 3.69–3.59 (m, 2 H), 1.93–1.85 (m, 2 H),
1.84–1.76 (m, 1 H), 1.75–1.69 (m, 2 H), 1.64–1.57 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 146.3, 144.7, 138.5, 135.0,
128.2, 127.5, 127.4, 118.7, 114.0, 108.7, 73.2, 72.8, 69.2,
66.8, 64.9, 55.8, 40.1, 38.5, 36.2; IR (neat): νmax = 3385,
2921, 2853, 1517, 1273, 1074, 1033, 747 cm–1. ESI-MS: m/z
= 381 [M + Na]+.
(2R,4R,6R)-2-[2-(Benzyloxy)ethyl]-6-[3-methoxy-4-
(methoxymethoxy)phenyl]-4-(methoxymethoxy)-
tetrahydro-2H-pyran (9)
[α]D25 +34.2 (c 1.04, CHCl3). 1H NMR (300 MHz, CDCl3):
δ = 7.29–7.16 (m, 5 H), 7.02 (d, J = 8.0 Hz, 1 H), 6.86–6.75
(m, 2 H), 5.13 (s, 2 H), 4.70–4.63 (m, 3 H), 4.43 (s, 2 H),
4.08–3.96 (m, 2 H), 3.78 (s, 2 H), 3.61–3.52 (m, 2 H), 3.43
(s, 3 H), 3.33 (s, 3 H), 1.99–1.88 (m, 1 H), 1.87–1.68 (m, 3
H), 1.67–1.57 (m, 1 H), 1.51–1.39 (m, 1 H). 13C NMR (75
MHz, CDCl3): δ = 149.6, 145.5, 138.6, 137.5, 128.2, 127.4,
127.3, 118.1, 116.2, 109.7, 95.4, 95.0, 73.7, 72.9, 70.1, 69.9,
66.8, 56.0, 55.7, 55.3, 38.4, 36.4, 36.2. IR (neat): νmax
=
© Georg Thieme Verlag Stuttgart · New York
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2927, 1513, 1267, 1153, 1037 cm–1. ESI-HRMS: m/z [M +
H]+ calcd for C25H34O7Na: 469.21792; found: 469.21967.
2-{(2R,4R,6R)-6-[3-Methoxy-4-(methoxymethoxy)-
phenyl]-4-(methoxymethoxy)tetrahydro-2H-pyran-2-
yl}ethanol (10)
(1S,2R)-1-{(2S,4S,6R)-6-[3-Methoxy-4-(methoxymethoxy)-
phenyl]-4-(methoxymethoxy)tetrahydro-2H-pyran-2-
yl}-2-[4-(methoxymethoxy)phenyl]ethane-1,2-diol (12)
[α]D25 +24.6 (c 0.44, CHCl3). 1H NMR (300 MHz, CDCl3):
δ = 7.32–7.28 (m, 2 H), 7.13 (d, J = 3.2 Hz, 1 H), 7.03–7.00
(m, 2 H), 6.91–6.86 (m, 2 H), 5.23 (s, 3 H), 5.16 (s, 3 H), 4.84
(d, J = 5.0 Hz, 1 H), 4.77 (dd, J = 1.6, 11.7 Hz, 1 H), 4.69 (s,
3 H), 4.17–3.69 (m, 1 H), 3.90 (s, 3 H), 3.52 (s, 3 H), 3.47 (s,
3 H), 3.32 (s, 3 H), 2.50–2.48 (m, 1 H), 2.02–1.94 (m, 1 H),
1.77–1.67 (m, 1 H), 1.63 (br s, OH, 1 H), 1.37–1.23 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 156.7, 149.7, 16.4, 134.2,
127.7, 118.2, 116.1, 109.7, 95.4, 95.1, 94.4, 74.7, 74.3, 73.6,
70.0, 56.1, 55.9, 55.4, 43.3, 37.9, 32.1, 29.6, 25.6. IR (neat):
[α]D25 +34.0 (c 0.65, CHCl3). 1H NMR (300 MHz, CDCl3):
δ = 7.03 (d, J = 8.3 Hz, 1 H), 6.84–6.74 (m, 2 H), 5.14 (s, 2
H), 4.72 (dd, J = 1.1, 11.3 Hz, 1 H), 4.67 (s, 2 H), 4.17–4.02
(m, 2 H), 3.81 (s, 3 H), 3.79–3.72 (m, 2 H), 3.44 (s, 3 H), 3.35
(s, 3 H), 2.03–1.94 (m, 1 H), 1.85–1.56 (m, 5 H). 13C NMR
(75 MHz, CDCl3): δ = 149.7, 145.7, 136.9, 118.0, 109.4,
95.4, 95.1, 74.2, 73.6, 69.9, 61.6, 56.0, 55.8, 55.4, 38.3, 37.8,
36.1. IR (neat): νmax = 3417, 2924, 1516, 1036 cm–1. ESI-
HRMS: m/z [M + H]+ calcd for C18H28O7Na: 379.17191;
found: 379.17272.
ν
max = 3449, 2925, 2852, 1512, 1266, 1153, 1076, 1036,
(2S,4R,6R)-2-(2-Iodoethyl)-6-[3-methoxy-4-
1000 cm–1. ESI-HRMS: m/z [M + H]+ calcd for
(methoxymethoxy)phenyl]-4-(methoxymethoxy)-
tetrahydro-2H-pyran (11)
C26H36O10Na: 531.21809; found: 531.22007.
(S)-1-{(2S,4S,6R)-6-[3-Methoxy-4-(methoxymethoxy)-
phenyl]-4-(methoxymethoxy)tetrahydro-2H-pyran-2-
yl}-2-[4-(methoxymethoxy)phenyl]ethanol (13)
[α]D25 +28.4 (c 0.34, CHCl3). 1H NMR (300 MHz, CDCl3):
δ = 7.10 (d, J = 8.2 Hz, 1 H), 6.97 (d, J = 1.9 Hz, 1 H), 6.88
(dd, J = 1.6, 8.2 Hz, 1 H), 6.86–5.89 (m, 1 H), 5.31 (m, 1 H),
5.12 (m, 1 H), 5.20 (s, 2 H), 4.81 (dd, J = 1.8, 11.7 Hz, 1 H),
4.76 (d, J = 0.9 Hz, 2 H), 4.47–4.42 (m, 1 H), 4.16–4.13 (m,
2 H), 3.89 (s, 3 H), 3.50 (s, 3 H), 3.43 (s, 3 H), 2.04–1.98 (m,
1 H), 1.94–1.90 (m, 1 H), 1.75–1.69 (dtd, J = 2.7, 11.9, 14.3
Hz, 1 H), 1.64–1.58 (dtd, J = 2.7, 11.7, 14.3, 1 H). 13C NMR
(75 MHz, CDCl3): δ = 149.6, 145.6, 139.0, 137.2, 118.2,
116.2, 4.8, 109.8, 95.5, 95.1, 73.9, 73.3, 70.0, 56.0, 55.8,
55.4, 38.2, 35.9. IR (neat): νmax = 2923, 2851, 1513, 1266,
1153, 1075, 1037 cm–1. ESI-HRMS: m/z [M + H]+ calcd for
C18H26O6Na: 361.16163; found: 361.16216.
[α]D25 +11.20 (c 0.87, CHCl3). 1H NMR (300 MHz, CDCl3):
δ = 7.19–7.09 (m, 3 H), 7.02–6.82 (m, 4 H), 5.23 (s, 2 H),
5.16 (s, 3 H), 4.81–4.64 (m, 3 H), 4.36–4.24 (m, 1 H), 4.25–
4.19 (m, 1 H), 3.89 (s, 3 H), 3.78–3.60 (m, 1 H), 3.51 (s, 3
H), 3.46 (s, 3 H), 3.37 (s, 3 H), 2.90–2.70 (m, 2 H), 2.51 (br
s, OH, 1 H), 2.08–1.87 (m, 2 H), 1.79–1.64 (m, 2 H). 13
C
NMR (75 MHz, CDCl3): δ = 155.7, 149.6, 137.0, 131.8,
130.7, 130.3, 128.7, 118.2, 116.2, 114.1, 109.7, 95.5, 95.1,
94.5, 77.0, 74.4, 74.0, 70.1, 56.1, 55.8, 55.4, 38.6, 38.3, 31.9.
IR (neat): νmax = 3450, 2925, 2854, 1636 cm–1. ESI-MS: m/z
= 515 [M + Na]+.
(2R,4R,6S)-2-[3-Methoxy-4-(methoxymethoxy)phenyl]-
4-(methoxymethoxy)-6-[(E)-4-(methoxymethoxy)styryl]-
tetrahydro-2H-pyran (2)
Rhoiptelol B (1):
Mp 65–67 °C; [α]D25 +87.4 (c 0.3, MeOH). 1H NMR (300
MHz, CD3OD): δ = 7.05 (br s, 1 H), 7.04 (d, J = 8.4 Hz, 2
H), 6.82 (dd, J = 8.4, 2.0 Hz, 1 H), 6.74 (d, J = 8.4 Hz, 1 H),
6.67 (d, J = 8.4 Hz, 2 H), 4.67 (dd, J = 10.7, 3.2 Hz, 1 H),
4.26 (t, J = 3.2 Hz, 1 H), 3.85 (s, 3 H), 3.80 (dt, J = 12.7, 2.9
Hz, 1 H), 3.59 (dt, J = 7.4, 3.2 Hz, 1 H), 2.84 (dd, J = 13.0,
6.6 Hz, 1 H), 2.67 (dd, J = 13.0, 7.4 Hz, 1 H), 1.91 (dd,
J = 13.3, 3.0 Hz, 1 H), 1.82 (dd, J = 14.3, 2.9 Hz, 1 H), 1.73
(ddd, J = 13.6, 10.9, 2.8 Hz, 1 H), 1.57 (dd, J = 13.6, 2.0 Hz,
1 H). 13C NMR (75 MHz, CD3OD): δ = 156.7, 148.8, 146.8,
136.2, 131.4, 131.3, 131.1, 119.8, 116.0, 115.8, 115.7,
111.1, 76.4, 75.2, 74.3, 65.7, 56.4, 41.2, 39.7, 35.0; IR
(neat): νmax = 3392, 2953, 2928, 1595, 1502, 1365, 1174,
1083, 854, 716 cm–1. ESI-HRMS: m/z [M + Na]+ calcd for
C20H24O6Na: 383.1470; found: 383.1461.
[α]D25 +6.4 (c 0.74, CHCl3). 1H NMR (300 MHz, CDCl3): δ
= 7.34–7.28 (m, 2 H), 7.11 (d, J = 8.8 Hz, 1 H), 7.01–6.89
(m, 4 H), 6.59 (d, J = 16.0 Hz, 1 H), 6.15 (d, J = 6.2, 16.0 Hz,
1 H), 5.21 (s, 2 H), 5.16 (s, 2 H), 4.89–4.82 (m, 1 H), 4.78 (s,
2 H), 4.65–4.55 (m, 1 H), 4.22–4.15 (m, 1 H), 3.90 (s, 3 H),
3.50 (s, 3 H), 3.47 (s, 3 H), 3.45 (s, 3 H), 2.06–1.94 (m, 2 H),
1.83–1.65 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ = 156.7,
149.6, 145.7, 137.1, 130.8, 129.6, 128.7, 127.5, 118.4,
116.3, 116.1, 109.9, 95.5, 95.1, 94.3, 74.1, 73.4, 70.1, 56.0,
55.9, 55.8, 55.4, 38.1, 36.3. IR (neat): νmax = 2925, 2852,
1511, 1266, 1235, 1152, 1077, 1037, 999 cm–1. ESI-HRMS:
m/z [M + H]+ calcd for C26H34O8Na: 497.21229; found:
497.21459.
Synlett 2014, 25, 661–664
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