Efficient synthesis of anhydrorhodovibrin and analogues

Article abstract of DOI:10.1055/s-0032-1317678

The synthesis of anhydrorhodovibrin and two analogues has been achieved in a highly efficient manner using a new Horner-Wadsworth-Emmons reagent bearing the Weinreb amide. Georg Thieme Verlag KG · Stuttgart · New York.

Full text of DOI:10.1055/s-0032-1317678

2980▌
LETTER
letter
Efficient Synthesis of Anhydrorhodovibrin and Analogues
Anhydrorhodovibrin and Analogues
a,b
b
b
a,b,c
a
OCARINA, Osaka City University, 3-3-138, Sugimoto, Sumiyoshi, Osaka 558-8585, Japan
b
Graduate School of Science, Osaka City University, Sugimoto, Sumiyoshi, Osaka 558-8585, Japan
Fax +81(6)66053153; E-mail: ohfune@sci.osaka-cu.ac.jp; E-mail: hassy@sci.osaka-cu.ac.jp
c
CREST/JST, 4-1-8, Honcho, Kawaguchi, Saitama 332-0012, Japan
Received: 25.09.2012; Accepted after revision: 30.10.2012
analysis of the peripheral and core light-harvesting pig-
ment–protein complexes (LH1 and LH2), reconstruction
of these pigments with various naturally occurring caro-
tenes and their spectroscopic analyses, and theoretical
Abstract: The synthesis of anhydrorhodovibrin and two analogues
has been achieved in a highly efficient manner using a new Horner–
Wadsworth–Emmons reagent bearing the Weinreb amide.
Key words: polyene, carotenoid, Horner–Wadsworth–Emmons
reaction, Weinreb amide
2
–5
studies have been performed. These studies have prov-
en that the intriguing supramolecular assembly consisted
of polypeptides, carotenoids, and bacteriochlorophyll a,
and provided deep insight into the photoenergy transfer-
Spirilloxanthin (1), anhydrorhodovibrin (2), and
spheroidene (4) are naturally occurring carotenoids that
play an important role in light harvesting processes of pur-
2–5
ring mechanism on a molecular structure level.
We have studied the molecular function of the LH1 com-
plex isolated from Rhodospirillum rubrum having all-
E-spirilloxanthin as the native carotenoid by absorption,
fluorescence excitation, and Stark absorption spectrosco-
1
ple photosynthetic bacteria (Figure 1). The energy trans-
fer mechanisms have received considerable attention and
inspired the development of highly efficient and environ-
5
2
py analyses. These studies have provided valuable infor-
mentally benign artificial photosynthetic energy devices.
mation with respect to the conformational details and
Various approaches involving the X-ray crystal structure
MeO
2
OMe
spirilloxanthin (1)
[
naturally occurring carotenoid, n = 13]
MeO
2
anhydrorhodovibrin (2)
[
naturally occurring carotenoid, n = 12]
MeO
2
dihydroanhydrorhodovibrin (3)
[
unnatural carotenoid, n = 11]
MeO
2
spheroidene (4)
[
naturally occurring carotenoid, n = 10]
MeO
n = No. of conjugated
double bonds
2
C30 carotenoid analogue (5)
unnatural carotenoid, n = 10]
[
Figure 1 Structures of carotenoids 1–5
SYNLETT 2012, 23, 2980–2984
Advanced online publication: 23.11.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1317678; Art ID: ST-2012-U0818-L
Georg Thieme Verlag Stuttgart · New York
©

LETTER
Anhydrorhodovibrin and Analogues
2981
charge distribution of the carotenoids as well as the inter- The synthetic plans of 2, 3 and 5 using 8 are depicted in
action between the carotenoids and apoproteins in the re- Scheme 2. The unsymmetrical carotenoids are divided
constructed LH1 complex. As part of our continuous into two fragments; i.e., the common C20 aldehyde 9 and
research program, we planned the extension of the above the right half phosphonium fragments 10, 11 and 12. The
biophysical studies using the reconstruction of the LH1 union of these fragments to form 2, 3 and 5 would be per-
analogues with the unsymmetrical carotenoids 2, 3 and 5 formed by the Wittig reaction. It is expected that the syn-
to gain an insight into the mechanism (Figure 1). These thesis of 9–12 would be effective by the iterative linkage
carotenoids share the same left C20 polyene side chain. of the new C5 synthon 8 with aldehydes 13–16.
Anhydrorhodovibrin (2) and dihydroanhydrorhodovibrin
We began the synthesis of the novel HWE reagent 8 by the
HWE olefination of 17 and the commercially available
N-methoxy-N-methylamide 18 (Scheme 3). The HWE
(3) are C40 carotenoids that simply differ from the num-
ber of conjugated double bonds (2: n = 12, 3: n =11). An-
alogue 5 consisted of thirty carbons in which the right
geranyl side chains in 1–4 were eliminated. The prepara-
tion of the novel carotenoids 3 and 5 depended on the syn-
thetic supply. Although the naturally occurring carotenoid
olefination reaction gave a 1.4:1 mixture of (E)-19 and
15
(
Z)-19 which was subjected to the Arbuzov reaction
with P(OEt) to give a 1.4:1 mixture of (E)-8 and (Z)-8.
3
The mixture was used in the next olefination step without
2
is prepared by extraction and purification from bacteria,
16
separation of the mixture. Having 8 in hand the synthesis
only a limited quantity of 2 has been available by the ex-
traction protocol. These facts led us to the synthetic stud-
ies of the target carotenoids.6
of the left fragment 9 was attempted. The HWE reaction
of 8 (a 1.4:1 mixture of stereoisomers) with the aldehyde
13 afforded a 1:3 mixture of (E)-20 and (Z)-20 in 97%
The synthetic study of carotenoids has been extensive due yield. The DIBAL-H reduction of the mixture in THF
7
–10
to their significant biological roles.
Based on the un- smoothly proceeded to afford a 1.3:1 mixture of the dienyl
symmetrical structural features of 2, 3, and 5, their synthe- aldehyde 21 in high yield (91% yield). The use of THF as
sis requires an efficient chain elongation to set up the left a solvent was crucial for the efficient conversion. Switch-
and right fragments with different types of functional ing to Et O gave rise to 21 in a much lower yield (67%)
2
groups. Among the various carotenoid synthetic methods along with the amide carbonyl group reduced product as
reported to date, we initially chose the widely utilized C5 the major by-product. The chain elongation using 8 was
synthon bearing ester 6 and nitrile 7 and attempted their it- repeated twice to furnish the common C20 fragment 9. It
1
1,12
erative linkages for the polyene chains (Scheme 1).
is noteworthy that the new chain elongation sequence us-
However, we recognized that the synthetic efficiency was ing 8 is advantageous to providing the reproducibility and
not satisfactory. The yields were found to be moderate to higher product yields in comparison to the nitrile 7 (see
1
3,14
poor in the late stages of the polyene elongation.
In Scheme 1). In addition, the preferential olefin isomeriza-
particular, reduction of the conjugated nitrile was prob- tion during the course of the chain elongation as well as
1
4
lematic in terms of the reproducibility. To overcome this the fact that all-E-carotenoids could be prepared by re-
obstacle, we postulated a new C5 synthon 8 bearing the crystallization along with the thermal isomerization reac-
8
,17
Weinreb amide. We expected that the nucleophile-accept- tions, suggested that a mixture of the E- and Z-isomers
1
6
ing feature by forming a stable chelating intermediate (A) of 8 can be used without separation of the mixture.
in situ would be responsible for improving the problemat-
ic reduction step.
The right segment 10 was effectively synthesized using
the new C5 unit 8 (Scheme 4). The commercially avail-
O
(
EtO)2P
EWG
1
) NaH, 7
MeO
CHO
known C5 synthons
2) DIBALH, –78 °C
73%*
6
7
EWG = CO2R
EWG = CN
MeO
MeO
CHO
*
CHO
n
For reduction of
n = 1: 61%*
n = 2: 31%*
-CN to -CHO
New C5 synthon
O
H
Al
OMe
O
O
O
OMe
N
(
EtO)2P
OMe
N
N
Me
H
Me
Me
(A)
8
Scheme 1 Initial attempts using 7 (upper) and the structure of new C5 synthon 8 (lower)
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2980–2984

2982
T. Yamada et al.
LETTER
target carotenoids 2, 3 and 5
MeO
CHO
2
common C20 left fragment 9
right half fragments
Ph3P
Br
10
Ph3P
Br
11
Ph3P
Br
12
MeO
O
O
O
O
13
14
(
EtO)2P
OMe
N
O
O
Me
8
15
16
Scheme 2 Synthetic plan
able 14 subjected to the HWE olefination reaction with 8
followed by the DIBAL-H reduction produced a conjugat-
ed aldehyde 23 in 79% yield (two steps from 14). A set of
these transformations was repeated to give 24 in 76%
yield (two steps from 23) which was converted to the
phosphonium salt 10 by the reduction to the correspond-
ing allyl alcohol 25 followed by treatment with
Cl
O
O
O
O
(
EtO)2P
OMe
17
X
OMe
N
N
LHMDS, THF
0 °C
18
P(OEt)3, KI
acetone, 50 °C
steps 93%
1
9 X = Cl, E/Z = 1.4:1
8
X =
P(OEt)2 , E/Z = 1.4:1
2
O
1
8
PPh ·HBr. The coupling reaction of the common left
3
fragment 9 and the right half fragment 10 smoothly pro-
ceeded with geometrical isomerization to give 2 in a high-
ly efficient manner. Flash column chromatography or
8
, NaH
THF
MeO
MeO
X
O
97%
13
2
DIBALH, THF
78 °C, 91%
20 X = CON(Me)OMe, E/Z = 1:3
21 X = CHO, E/Z = 1.3:1
–
1) 8, NaH
THF
E/Z = 1:1
E/Z = 4.2:1
1) olefination with 8
14
OHC
2) DIBALH
2) DIBALH
2
steps 83%
THF, –78 °C
23
2
steps, 79%
MeO
CHO
E/Z = 1.1:1
1
) olefination with 8
2) DIBAL
E/Z = 1:1
E/Z = 3.9:1
E/Z = 3.7:1
X
22
2
steps, 76%
1) olefination with 8
2
2
1
4 X = CHO
5 X = CH2OH
0 X = CH2PPh3 Br
DIBALH, THF, –78 °C, 67%
2) DIBALH
2
steps 78%
PPh ⋅HBr, CH Cl , 0 °C
3
2
2
MeO
9
, NaH
CHO
THF, reflux
E/Z = 3.7:1
E/Z = 1.1:1
2 steps, 42%
9
anhydrorhodovibrin (2)
Scheme 3 Synthesis of 8 and the common C-20 fragment 9
Synlett 2012, 23, 2980–2984
Scheme 4 Synthesis of anhydrorhodovibrin (2)
© Georg Thieme Verlag Stuttgart · New York

LETTER
Anhydrorhodovibrin and Analogues
2983
HPLC on silica gel of the mixture was not suitable to fur-
nish sufficient amounts of the carotenoids due to their in-
stability. Therefore, we attempted a scaled-up synthesis
and purification by recrystallization to prepare the all-
E-carotenoids. As a result, 130 mg of the all-E-anhy-
drorhodovibrin (2) was obtained after rapid filtration of
the mixture through a thin silica gel pad followed by re-
crystallization from hexane–EtOAc. The spectroscopic
(2) (a) Cazzonelli, C. Funct. Plant Biol. 2011, 38, 833.
(
b) Maoka, T. Mar. Drug 2011, 9, 278. (c) Rao, A. V.; Rao,
L. G. Pharmacol. Res. 2007, 55, 207.
(
3) (a) McDermott, G.; Prince, S. M.; Freer, A. A.;
Hawthornthwaite-Lawless, A. M.; Papiz, M. Z.; Cogdell, R.
J.; Isaacs, N. W. Nature (London) 1995, 374, 517.
(b) Roszak, A. W.; Howard, T. D.; Southall, J.; Gardiner, A.
T.; Law, C. J.; Isaacs, N. W.; Cogdell, R. J. Science 2003,
302, 1969.
(4) (a) Akahane, J.; Rondonuwu, F. S.; Fiedor, L.; Watanabe,
Y.; Koyama, Y. Chem. Phys. Lett. 2004, 393, 184.
data of the synthetic anhydrorhodovibrin (2) were identi-
cal to those of the authentic data.19
(
b) Kakitani, Y.; Akahane, J.; Ishii, H.; Sogabe, H.; Nagae,
Preparation of the all-E-stereoisomers of the new carot-
enoid analogues 3 and 5 was completed in the same man-
H.; Koyama, Y. Biochemistry 2007, 46, 2181. (c) Iida, K.;
Inagaki, J.; Shinohara, K.; Suemori, Y.; Ogawa, M.; Dewa,
T.; Nango, M. Langmuir 2005, 21, 3069. (d) Cogdell, R. J.;
Gall, A.; Köhler, J. Rev. Biophys. 2006, 39, 227.
ner (Scheme 5). The NMR analyses of 3 and 5 confirmed
their all-E-stereochemistries.20,21
(
5) (a) Nakagawa, K.; Suzuki, S.; Fujii, R.; Gardiner, A. T.;
Cogdell, R. J.; Nango, M.; Hashimoto, H. J. Phys. Chem. B
Br
2
008, 112, 9467. (b) Nakagawa, K.; Suzuki, S.; Fujii, R.;
Ph3P
Gardiner, A. T.; Cogdell, R. J.; Nango, M.; Hashimoto, H.
Photosynth. Res. 2008, 95, 339. (c) Horibe, T.; Nakagawa,
K.; Kusumoto, T.; Fujii, R.; Cogdell, R. J.; Nango, M.;
Hashimoto, H. Acta Biochim. Pol. 2012, 59, 97.
15
11
9
, NaH
THF, reflux
0% from 15
(
d) Yamamoto, M.; Horibe, T.; Nishisaka, Y.; Suzuki, S.;
1
Kozaki, M.; Fujii, R.; Doe, M.; Nango, M.; Okada, K.;
Hashimoto, H. Bull. Chem. Soc. Jpn. 2012, ;in press; DOI:
dihydroanhydrorhodovibrin (3)
1
0.1246/bcsj.20120230.
Br
(
(
6) Surmatis, J. D.; Ofner, A.; Gibas, J.; Thommen, R. J. Org.
Chem. 1966, 31, 186.
7) (a) Laudrum, J. T. Carotenoids: Physical, Chemical and
Biological Functions and Properties; CRC Press: Boca
Raton, 2010. (b) Thirsk, C.; Whiting, A. J. Chem. Soc.,
Perkin Trans. 1 2002, 999.
Ph3P
16
12
9
, NaH
THF, reflux
6% from 16
1
(8) (a) Carotenoids, Volume 2: Synthesis; Britton, G.; Liaaen-
Jensen, S.; Pfander, H., Eds.; Birkhäuser: Basel, 1996.
C30 analog 5
(
b) Ito, M.; Yamano, Y.; Tode, C.; Wada, A. Arch. Biochem.
Biophys. 2009, 483, 224. (c) Ernst, H. Pure Appl. Chem.
002, 74, 2213.
9) For the synthesis of symmetrical related carotenoid, see:
a) Isler, O.; Lindlar, H.; Montavon, M.; Rüegg, R.; Zeller,
Scheme 5 Synthesis of analogues 3 and 5
2
(
In conclusion, we have developed a new HWE reagent 8
bearing the Weinreb amide. The synthetic utility was dis-
played by the synthesis of unsymmetrical carotenoids 2, 3
and 5 on a 100-mg scale. Reconstruction of LH1 analogue
with 2, 3 and 5, and their spectroscopic analyses are cur-
rently underway.
(
P. Helv. Chim. Acta 1956, 39, 449. (b) McMurry, J. E.;
Fleming, M. P. J. Am. Chem. Soc. 1974, 96, 4708. (c) Ito,
M.; Masahara, R.; Tsukida, K. Tetrahedron Lett. 1977,
2767. (d) Akiyama, S.; Nakatsuji, S.; Eda, S.; Kataoka, M.;
Nakagawa, M. Tetrahedron Lett. 1979, 2813. (e) Haag, A.;
Eugster, C. H. Helv. Chim. Acta 1982, 65, 1795. (f) Ji, M.;
Choi, H.; Park, M.; Kee, M.; Jeong, Y. C.; Koo, S. Angew.
Chem. Int. Ed. 2001, 40, 3627. (g) Vaz, B.; Alvarez, R.; de
Lera, A. R. J. Org. Chem. 2002, 67, 5040. (h) Choi, S.; Koo,
S. J. Org. Chem. 2005, 70, 3328. (i) Kajikawa, T.; Iguchi,
N.; Katsumura, S. Org. Biomol. Chem. 2009, 7, 4586.
Acknowledgment
The present work was supported by JST/CREST and was partially
supported by a Grant-in-Aid for Scientific Research from the Mini-
stry of Education, Culture, Sports, Science and Technology
(j) Fontán, N.; Domínguez, M.; Álvarez, R.; de Lera, Á. R.
(MEXT), Japan and AOARD.
Eur. J. Org. Chem. 2011, 6704. (k) Fontán, N.; Álvarez, R.;
de Lera, A. R. J. Nat. Prod. 2012, 75, 975.
(
10) For the synthesis of unsymmetrical related carotenoid, see:
Supporting Information for this article is available online at
(
(
(
a) Zeng, F.; Negishi, E. Org. Lett. 2001, 3, 719.
b) Yamano, Y.; Ito, M. Chem. Pharm. Bull. 2001, 49, 1662.
c) Yamano, Y.; Sakai, Y.; Hara, M.; Ito, M. J. Chem. Soc.,
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
n
ungIifoop
r
t
Perkin Trans. 1 2002, 2006. (d) Yamano, Y.; Ito, M. Chem.
Pharm. Bull. 2004, 52, 780. (e) Yamano, Y.; Ito, M. Org.
Biomol. Chem. 2007, 5, 3207. (f) Yamano, Y.; Ito, M.;
Wada, A. Org. Biomol. Chem. 2008, 6, 3421. (g) Khachik,
F.; Chang, A.-N. J. Org. Chem. 2009, 74, 3875. (h) Yamano,
Y.; Chary, M. V.; Wada, A. Chem. Pharm. Bull. 2010, 58,
References
(1) (a) Fiedor, L.; Akahane, J.; Koyama, Y. Biochemistry 2004,
4
3, 16487. (b) Fujii, R.; Onaka, K.; Kuki, M.; Koyama, Y.;
Watanabe, Y. Chem. Phys. Lett. 1998, 288, 847. (c) Fujii, R.;
Ishikawa, T.; Koyama, Y.; Taguchi, M.; Isobe, Y.; Nagae,
H.; Watanabe, Y. J. Phys. Chem. A 2001, 105, 5348.
1
362.
(
d) Zhang, J.-P.; Nagae, H.; Qian, P.; Limantara, L.; Fujii,
R.; Watanabe, Y.; Koyama, Y. J. Phys. Chem. B 2001, 105,
312.
(
11) (a) Pommer, H. Angew. Chem. 1960, 72, 811. (b) Magoulas,
G. E.; Bariamis, S. E.; Athanassopoulos, C. M.;
7
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2980–2984

2984
T. Yamada et al.
LETTER
Haskopoulos, A.; Dedes, P.; Krokidis, M. G.; Karamanos, N.
K.; Kletsas, D.; Papaioannou, D.; Maroulis, G. Eur. J. Med.
Chem. 2011, 46, 721.
(18) (a) Bestmann, H. J.; Ermann, P.; Ruppel, H.; Sperling, W.
Liebigs Ann. Chem. 1986, 479. (b) Sliwka, H.-R.; Nokleby,
O. W.; Liaaen-Jensen, S. Acta Chem. Scand., Ser. B 1987,
41, 245. (c) Rüegg, R.; Schwieter, U.; Ryser, G.; Schüdel,
P.; Isler, O. Helv. Chim. Acta 1961, 44, 985.
(
(
(
12) (a) Johan, L. Pure Appl. Chem. 1985, 57, 753. (b) Creemers,
A. F. L.; Lugtenburg, J. J. Am. Chem. Soc. 2002, 124, 6324.
c) van Wijik, A. A. C.; van de Weerd, M. B.; Lugtenburg, J.
(
(19) Qian, P.; Saiki, K.; Mizoguchi, T.; Hara, K.; Sashima, T.;
Fujii, R.; Koyama, Y. Photochem. Photobiol. 2001, 74, 444.
Eur. J. Org. Chem. 2003, 863.
1
13) (a) Domínguez, M.; Álvarez, R.; Martras, S.; Farrés, J.;
Parés, X.; de Lera, A. R. Org. Biomol. Chem. 2004, 2, 3368.
(20) (R)-3: H NMR (600 MHz, C D ): δ = 6.60–6.79 (m, 5 H),
6
6
6.51 (d, J = 13.8 Hz, 1 H), 6.50 (d, J = 14.4 Hz, 1 H), 6.49
(d, J = 14.4 Hz, 1 H), 6.24–6.38 (m, 7 H), 5.91 (dt, J = 15.6,
7.2 Hz, 1 H), 5.75 (dt, J = 15.6, 7.2 Hz, 1 H), 5.24 (m, 1 H),
3.08 (s, 3 H), 2.32 (d, J = 7.2 Hz, 2 H), 2.20 (dt, J = 13.8, 7.2
Hz, 1 H), 1.97–2.15 (m, 3 H), 1.90 (s, 3 H), 1.89 (s, 3 H),
1.89 (s, 3 H), 1.88 (s, 6 H), 1.69 (s, 3 H), 1.60 (s, 3 H), 1.54–
1.60 (m, 1 H), 1.44–1.51 (m, 1 H), 1.19–1.29 (m, 1 H), 1.10
(b) Domínguez, M.; Álvarez, R.; Borrás, E.; Farrés, J.;
Parés, X.; de Lera, A. R. Org. Biomol. Chem. 2006, 4, 155.
14) (a) Tanaka, K.; Struts, A. V.; Krane, S.; Fujioka, N.;
Salgado, G. F. J.; Martinez-Mayorga, K.; Brown, M. F.;
Nakanishi, K. Bull. Chem. Soc. Jpn. 2007, 80, 2177.
(
b) Valla, A.; Valla, B.; Le Guillou, R.; Cartier, D.; Dufosse,
1
3
L.; Labia, R. Helv. Chim. Acta 2007, 90, 512. (c) Laptev, A.
V.; Belikov, N. E.; Lukin, A. Y.; Barachevskii, V. A.;
Alfimov, M. V.; Demina, O. V.; Varfolomeev, S. D.; Shvets,
V. I.; Khodonov, A. A. High Energy Chem. 2008, 42, 601.
15) NaH in THF, DBU with LiCl in MeCN, LDA in THF or
NaNH in CH Cl did not affect the E/Z selectivity.
(s, 6 H), 0.95 (d, J = 6.6 Hz, 3 H). C NMR (150 MHz,
C D ): δ = 138.5, 138.0, 137.9, 137.7, 136.9, 136.8, 136.7,
6
6
136.3, 135.7, 135.6, 133.6, 133.3, 133.1, 131.3, 131.0 (2 ×
C), 130.8, 130.6, 128.7, 128.3, 126.1, 125.6, 125.3, 125.2,
74.7, 49.1, 44.6, 41.1, 37.2, 33.4, 26.1, 25.8, 24.9, 19.7, 17.7,
(
(
+
13.1 (2 × C), 12.9 (2 × C), 12.8. HRMS (EI): m/z [M] calcd
2
2
2
+
25.1
16) Geometrical isomers of 19 were separable by silica gel
column chromatography. The Arbuzov reaction of (E)-19
and (Z)-19 gave (E)-8 and (Z)-8, respectively without any
isomerization. The olefination of 13 with E-isomer 8 and Z-
isomer 8 were examined, respectively, to provide a 1:3
mixture of 20.
17) The isomerization process to provide the E-conjugated
double bond (C10 and C11) of 9 during the course of
polyene chain elongation is interesting. We speculate that
the isomerization could be triggered by means of the thermal
isomerization. However, other possibilities such as
photoisomerization and a base-catalyzed isomerization
during the course of the HWE and Wittig reaction conditions
as well as their complementary effects could not be ruled
out.
for [C H O] : 568.4644; found: 568.4645; [α]
+51.0 (c
4
1
60
D
= 0.1, CHCl ).
3
1
(21) 5: H NMR (600 MHz, CDCl ): δ = 6.55–6.66 (m, 4 H), 6.48
3
(dd, J = 15.0, 11.1 Hz, 1 H), 6.37 (d, J = 15.6 Hz, 1 H), 6.35
(d, J = 15.0 Hz, 1 H), 6.26 (d, J = 10.2 Hz, 1 H), 6.17–6.24
(3 H), 6.16 (d, J = 15.5 Hz, 1 H), 6.10 (d, J = 11.4 Hz, 1 H),
5.94 (d, J = 11.1 Hz, 1 H), 5.71 (dt, J = 15.5, 7.4 Hz, 1 H),
3.23 (s, 3 H), 2.32 (d, J = 7.4 Hz, 2 H), 1.98 (s, 3 H), 1.96 (s,
3 H), 1.94 (s, 3 H), 1.92 (s, 3 H), 1.82 (s, 3 H), 1.81 (s, 3 H),
(
1
3
1.15 (s, 6 H). C NMR (150 MHz, CDCl ): δ = 137.9, 137.5
3
(2 × C), 136.6, 136.2, 136.1, 135.9, 135.2, 134.8, 133.0,
132.6, 131.4, 130.6, 130.3, 129.3, 126.0, 125.3, 125.1,
124.8, 124.6, 75.1, 49.3, 43.6, 26.3, 24.9, 18.6, 13.0, 12.9,
+
+
12.8 (2 × C). HRMS (FAB): m/z [M] calcd for [C H O] :
3
1
44
432.3392; found: 432.3390.
Synlett 2012, 23, 2980–2984
© Georg Thieme Verlag Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or
emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.
However, users may print, download, or email articles for individual use.