Stereoselective synthesis of (+)-paeonilide and confirmation of its absolute configuration

Article abstract of DOI:10.1055/s-2006-939698

The first diastereoselective synthesis of paeonilide, a novel anti-PAF-active monoterpenoid, starting from R-(-)-carvone was reported. The absolute configuration for paeonilide was also established. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-939698

LETTER
1051
Stereoselective Synthesis of (+)-Paeonilide and Confirmation of its Absolute
Configuration
Stereoselective
S
h
e
)-Paeonilid
n
e
ying Wang,a,b Hongbin Zhang,*b Jikai Liu,a Yanhua Ji,b Zhihui Shao,b Liang Lib
a
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of
Sciences, Kunming, Yunnan 650204, Graduate School of Chinese Academy of Science, Beijing 100039, P. R. of China
b
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Pharmacy, Yunnan University,
Kunming, Yunnan 650091, P. R. of China
Fax +86(871)5035538; E-mail: zhanghb@ynu.edu.cn
Received 8 January 2006
R
H
H
H
H
Abstract: The first diastereoselective synthesis of paeonilide, a
novel anti-PAF-active monoterpenoid, starting from R-(–)-carvone
was reported. The absolute configuration for paeonilide was also
established.
O
O
HO
O
HO
O
O
O
Key words: diastereoselective synthesis, (+)-paeonilide, absolute
configuration, monoterpenoid, carvone
Paeonilactone A, R = H
Paeonilactone C, R = OBz
Paeonilactone B
O
H
O
Paeonia root bark, ‘mu-dan-pi’ or ‘dan-pi’ in Chinese, is
one of the most important herbal drugs used in traditional
Chinese medicine. Representative chemical constituents
isolated from different species of Paeonia are a number of
structurally related monoterpenes that feature with a high-
ly oxygenated cyclohexane nucleus (Figure 1).1 In 2000,
a novel monoterpenoid, named paeonilide, was isolated
from the roots of Paeonia delavayi.2 Its new skeleton was
established by a combination of spectroscopic and X-ray
crystallographic analysis. The bioassay indicated that pae-
onilide selectively inhibited the platelet aggregation in-
duced by PAF (the platelet activating factor) with an IC50
value of 8 mg/mL, with no inhibitory effect on ADP- or
AA-induced platelet aggregation. Due to its important
biological activity as well as its potential to be developed
to a new lead for medicinal chemistry, synthesis of
paeonilide and its analogues were thus initiated. In this
communication, we report the first diastereoselective syn-
thesis of paeonilide.
O
O
O
Paeonilide
O
Figure 1 Examples of tetrahydrofuran containing natural products.
thus investigated. Starting from (R)-(–)-carvone, a
bromination reaction was carried out with NBS following
a literature procedure.4 The allylic bromide 5 was then
subjected to an SN2 substitution with silver acetate in
acetic acid to give an allylic acetate 6. Luche reduction5
with sodium borohydride and following by MCPBA
epoxidation6 of the resultant hydroxyalkene 7 afforded
epoxide 8 in 88% yield over two steps (Scheme 2). The
epoxide was initially treated with lithium bromide by fol-
lowing a literature procedure.7 Unfortunately no desired
Inspection of paeonilide revealed that it could be synthe-
sized from a highly oxygenated carvone derivative 3,
which could be prepared from commercially available
(R)-(–)-carvone. The retrosynthetic analysis is shown in
Scheme 1.
O
O
H
O
RO
O
H
O
O
O
O
1
O
1
O
Although intermediate 3 had been synthesized in the liter-
ature by an 8-step procedure in 27% overall yield,3
utilization of organic selenium as well as expensive cate-
cholborane made the process less attractive to us. An
alternative way toward the synthesis of intermediate 3 was
O
Paeonilide
7
O
2
O
OH
O
6
5
O
3
3
2
4
O
10
9
HO
OH
8
HO
OH
(R)-(–)-Carvone
SYNLETT 2006, No. 7, pp 1051–1054
Advanced online publication: 24.04.2006
0
3.
0
5.
2
0
0
6
Scheme 1 Retrosynthetic analysis of paeonilide from (R)-(–)-carvone.
DOI: 10.1055/s-2006-939698; Art ID: W00706ST
© Georg Thieme Verlag Stuttgart · New York

1052
C. Wang et al.
LETTER
product was observed. The opening of epoxide was finally
achieved with lithium bromide generated in situ from re-
acting n-butyllithium with acetyl bromide in anhydrous
THF. After protection of the diol system with dimethoxy
propane (DMP) in the presence of catalytic ammount of
p-toluenesulfonic acid, compound 10 was put to a hydro-
boration with borane-dimethyl sulfide complex. To our
delight, the 1,3-diol was produced in high yield with no
hydrolysis of the bromo moiety in the ring system. The
1,3-diol compound was then directly treated with potassi-
um tert-butoxide in DMF and cyclohexene derivative 3
was obtained in good isolated yield. Our modification led
to intermediate 3 from (R)-(–)-carvone in a total 22%
yield over 8 steps (Scheme 2).
O
O
O
O
O
OH
OH
a
O
O
3
12
b, c
O
O
O
O
O
O
+
O
O
O
13
3.5:1
14
Scheme 3 Introduction of C5 oxy function by hydroboration.
Reagents and conditions: a) DMP, CH2Cl2, TsOH, 40 °C, 95%; b)
BH3·SMe2, THF, H2O2 (30%), 6 N NaOH; c) CrO3, pyridine, CH2Cl2,
60%.
O
O
OH
O
R
OH
a
c
d
ate 15 was established by NOE experiment. The primary
alcohol was converted to benzoyl ester 16, and the ketal
protecting group was removed in the presence of 6 N HCl
in methanol at room temperature.
OAc
OAc
5: R = Br
6: R = OAc
(R)-(–)-Carvone
b
7
8
BzO
e
O
OH
H
H
O
H
H
O
O
O
O
O
O
O
O
OH
a
b
Br
OH
O
O
Br
Br
O
g
O
f
h
OH
HO
Br
Br
15
16
3
OH
OAc
HO
OH
OAc
c
H
OH
11
O
H
3
10
9
OBz
H
O
OBz
OBz
H
H
H
Scheme 2 Synthesis of intermediates for paeonilide.
HO
d
HO
Reagents and conditions: a) NBS, NaOAc, AcOH, CH2Cl2, 35%; b)
AgOAc, acetone, reflux, 92%; c) NaBH4, CeCl3, MeOH, 95%; d)
MCPBA, CH2Cl2, NaHCO3, 93%; e) LiBr, generated in situ, THF,
AcOH, 97%; f) DMP, CH2Cl2, TsOH, 40 °C, 95%; g) BH3·SMe2,
THF, H2O2 (30%), 6 N NaOH, 89%; h) t-BuOK, DMF, 95%.
O
O
O
HO
O
H
H
Br
H
Br
Br
17
19
18
e
HO
O
H
OBz
H
H
OBz
With the 9,10-diol 3 in hand, introduction of an oxy func-
tion to the C5-position of the ring system was initiated.
After protection of the 1,3-diol system as an acetonide, a
Brown hydroboration reaction was conducted. Hydro-
boration of compound 12 led to an inseparable mixture of
regioisomers (Scheme 3). The mixture was further oxi-
dized with CrO3 in pyridine to afford two ketone isomers.
To our disappointment, the major product was the isomer
with oxy function being introduced at the C6-position, and
only a small amount of desired C5-ketone 14 was formed.
This approach was therefore abandoned.
O
O
O
O
O
H
O
H
Br
21
20
Scheme 4 Introduction of C5 oxy function by bromoetherification.
Reagents and conditions: a) NBS, THF, 95%; b) BzCl, pyridine,
CH2Cl2, 99%; c) 6 N HCl, MeOH, 92%; d) NaIO4, acetone–H2O,
65%; e) NaIO4, KMnO4, acetone–H2O, 58%.
With diol 17 in hand, we came to the final stage of our to-
tal synthesis. Cleavage of diol 17 with sodium periodate
in acetone and water (3:1) at room temperature led to a cy-
clopentane derivative 18 rather than expected aldehyde
19. On the other hand, treatment of diol 17 with sodium
periodate in the presence of a secondary oxidative agent
such as potassium permanganate in acetone resulted in a
lactone 20 which was formed by a concomitant intra-
molecular lactonization. Although the highly substituted
Having failed to introduce the key oxy function to the C5-
position, a bromoetherification was then carried out by
treatment of diol 3 with NBS in anhydrous THF at room
temperature (Scheme 4). The desired furan derivative 15
was obtained in nearly quantitative yield with excellent
diastereoselectivity.8 We observed only one diastereoiso-
mer in this cyclization reaction and this transformation
represents a good example of diastereotopic group selec-
tive reaction.9 The relative configuration of the intermedi-
Synlett 2006, No. 7, 1051–1054 © Thieme Stuttgart · New York

LETTER
Stereoselective Synthesis of (+)-Paeonilide
1053
cyclopentane derivative 18 could be used as a valuable in- In summary, the first diasteroselective synthesis of
termediate for the synthesis of iridoid type natural prod- paeonilide, a PAF inhibitory agent, was completed in 16
uct,10 it was not a desired compound in this synthesis. The steps with 6.2% overall yield. Some important intermedi-
cis-diol was thus oxidized with IBX in ethyl acetate11 at ates for the synthesis of iridoid natural products were also
refluxing temperature to provide a ketone 22 (Scheme 5). obtained in this research.13 The proposed absolute con-
Utilization of periodic acid in ethyl acetate, oxidative figuration of paeonilide was also confirmed by this syn-
cleavage of a-hydroxyl ketone 22 was achieved and thesis. Synthetic study towards iridoid natural product by
afforded a free acid 21, which was treated with di- utilization of this methodology is currently underway in
azomethane to form the corresponding methyl ester 23. It our laboratory.
was noteworthy that methyl ester 23 existed as a mixture
of diastereoisomers probably due to an enol epimerization
process. Dehydrobromination of a-bromo ketone with
Acknowledgment
This work was partially supported by a Grant (20272049) from
National Natural Science Foundation of China and a Grant from the
foundation of the Chinese Ministry of Education for the promotion
of Excellent Young Scholar. We would like to thank the Inter-
national Cooperation Division of Yunnan provincial Science &
Technology Department for partial financial support (2002GH04).
DBU in refluxing benzene finally provided the key inter-
mediate 1 (R = Me), an unstable a,b-unsaturated ketone,
in moderate yield. Although furanyl ketone 1 could be pu-
rified by chromatography, it was better used in the next
step without further purification. After removal of
benzene, the residue was treated with 6 N HCl (excess) in
ethyl acetate at room temperature and paeonilide was
obtained by a cyclization reaction.
References and Notes
(1) (a) Hayashi, T.; Shinbo, T.; Shimizu, M.; Arisawa, M.;
Morita, N.; Kimura, M.; Matsuda, S.; Kikuchi, T.
Tetrahedron Lett. 1985, 26, 3699. (b) Rönn, M.; Andersson,
P. G.; Bäckvall, J. E. Acta Chem. Scand. 1998, 52, 524.
(c) Jonasson, C.; Rönn, M.; Bäckvall, J. E. J. Org. Chem.
2000, 65, 2122.
(2) Liu, J. K.; Ma, Y. B.; Wu, D. G.; Lu, Y.; Shen, Z. Q.; Zheng,
Q. T.; Chen, Z. H. Biosci. Biotechnol. Biochem. 2000, 64,
1511.
OBz
H
OBz
H
R
HO
O
R
a
O
HO
O
HO
H
Br
H
Br
17
22
OMe
b
BzO
(3) (a) Hatakeyama, S.; Kawamura, M.; Takano, S.; Irie, H.
Tetrahedron Lett. 1994, 35, 7993. (b) Hatakeyama, S.;
Kawamura, M.; Shimanuki, E.; Takano, S. Tetrahedron Lett.
1992, 33, 333.
(4) (a) Srikrishna, A.; Hemamalini, P. J. Org. Chem. 1990, 55,
4883. (b) For a high-yielding procedure leading to
compound 6, see: Engel, W. J. Agric. Food Chem. 2001, 49,
4069.
O
O
MeO
O
H
R
H
OBz
c
R
R
R
O
O
O
H
Br
23
1
(5) Luche, J. L. J. Am. Chem. Soc. 1978, 100, 2226.
(6) Rao, A. S.; Paknikar, S. K.; Kirtane, J. G. Tetrahedron 1983,
39, 2323.
d
(7) Bajwa, J. S.; Anderson, R. C. Tetrahedron Lett. 1991, 32,
3021.
OMe
OMe
BzO
BzO
BzO
(8) In the synthetic work published in ref. 3, discriminating
between the two primary hydroxyl groups was achieved by
an enzymatic acetylation towards substrate 3 and
diastereoisomeric monoacetate of diol 3 was obtained with a
ratio of 13: 1. In our case, bromoetherification of diol 3 led
to only desired diastereisomer 15.
O
O
H
R
H
R
H
R
OH
O
HO
OH
O
O
O
O
O
O
(9) (a) Hoffmann, R. W. Synthesis 2004, 2075. (b) Studer, A.;
Schleth, F. Synlett 2005, 3033.
Scheme 5 Synthesis of paeonilide, the final stage.
(10) Boros, C. A.; Stermitz, F. R. J. Nat. Prod. 1990, 53, 1055.
(11) More, J. D.; Finney, N. S. Org. Lett. 2002, 4, 3001.
(12) Natural paeonilide was provided by professor J. K. Liu. The
optical rotation of synthetic paeonilide compared well to the
value of authentic sample.
Reagents and conditions: a) IBX, EtOAc, 90%; b) H5IO6, EtOAc;
then diazomethane in Et2O, 90%; c) DBU, benzene, reflux; d) 6 N
HCl, EtOAc, r.t., 40%.
(13) Compound 3: colorless solid; mp 84–85 °C; [a]D20 –101.6 (c
0.993, CHCl3). IR (film): 3424 (s), 2928 (m), 1632 (m), 1372
(m), 1297 (m), 1281 (m), 1237 (w), 1136 (s), 1099 (w), 1071
(w), 1034 (w) cm–1. 1H NMR (300 MHz, CDCl3): d = 5.67 (1
H, dd, J = 3.9, 10.4 Hz), 5.58 (1 H, d, J = 10.4 Hz), 4.03 (1
H, br s), 3.92–3.74 (4 H, m), 3.12 (1 H, br s), 2.70 (1 H, br
s), 2.49–2.20 (2 H, m), 1.96 (1 H, m), 1.91 (1 H, ddd, J = 2.8,
Although the absolute configuration of paeonilide could
be derived biosynthetically from p-menthane, no solid
evidence was obtained due to the scarcity of available
1
sample. Our synthetic sample has identical IR, H NMR
and 13C NMR spectra, most of all, the optical rotation
compared well to those of an authentic sample.12 There-
fore this synthesis also established the absolute configura-
tion unambiguously for paeonilide.
8.3, 15.6 Hz), 1.38 (3 H, s), 1.35 (3 H, s), 1.30 (3 H, s). 13
C
NMR (75 MHz, CDCl3): d = 131.7 (d), 128.9 (d), 108.5 (s),
Synlett 2006, No. 7, 1051–1054 © Thieme Stuttgart · New York

1054
C. Wang et al.
LETTER
78.3 (d), 77.6 (s), 64.4 (t), 63.9 (t), 46.6 (d), 30.1 (d), 28.3
(q), 27.9 (q), 25.1 (q), 24.9 (t). MS (EI): m/z (%) = 242 (3)
[M+], 227 (3), 211 (5), 191 (13), 167 (52), 149 (36), 105 (91),
57 (100). HRMS: m/z calcd for C13H22O4Na [M + 23]+:
265.1415; found: 265.1416.
(w), 1451 (w), 1275 (s), 1112 (s), 1071 (w), 1045 (w), 713
(s) cm–1. 1H NMR (300 MHz, CDCl3): d = 7.98 (2 H, d,
J = 8.4 Hz), 7.56 (1 H, t, J = 7.5 Hz), 7.44 (2 H, dd, J = 7.5,
8.4 Hz), 4.51 (1 H, dd, J = 7.1, 8.3 Hz), 4.33 (2 H, d, J = 6.0
Hz), 4.22 (1 H, t, J = 9.0 Hz), 4.08 (1 H, d, J = 9.0 Hz), 3.79
(1 H, dd, J = 8.0, 9.1 Hz), 2.93 (1 H, dd, J = 8.0, 16.5 Hz),
Compound 15: colorless oil; [a]D20 –4.9 (c 0.745, CHCl3). IR
(KBr): 3443 (br s), 2985 (s), 2937 (s), 2876 (s), 1458 (s),
1380 (s), 1256 (s), 1215 (s), 1103 (s), 1071 (s), 1029 (s), 990
cm–1. 1H NMR (300 MHz, CDCl3): d = 4.20–4.06 (4 H, m),
3.70–3.57 (3 H, m), 2.28–2.12 (4 H, m), 1.77–1.65 (1 H, m),
1.48 (3 H, s), 1.43 (3 H, s), 1.41 (3 H, s). 13C NMR (75 MHz,
CDCl3): d = 109.5 (s), 83.3 (d), 81.1 (s), 79.4 (d), 69.6 (t),
63.4 (t), 61.3 (d), 48.7 (d), 38.4 (d), 30.9 (t), 28.3 (q), 26.4
(q), 23.3 (q). MS (EI): m/z (%) = 322 (3) [M+], 320 (2) [M+],
307 (8), 305(7), 197 (7), 183 (10), 169 (12), 155 (16), 127
(27), 111 (27), 97 (38), 85 (64), 71 (100). HRMS: m/z calcd
for C13H22O4Na [M + 23]+: 343.0520; found: 343.0529.
Compound 16: colorless oil; [a]D20 –5.7 (c 0.764, CHCl3). IR
(KBr): 2981 (s), 2953 (s), 2876 (s), 1724 (s), 1688 (s), 1602
(m), 1582 (m), 1453 (s), 1424 (s), 1380 (s), 1325 (s), 1285
(s), 1211 (s), 1180 (s), 1113 (s), 1056 (s), 934 (s), 708 (s)
cm–1. 1H NMR (300 MHz, CDCl3): d = 7.98 (2 H, d, J = 7.5
Hz), 7.55 (1 H, t, J = 7.5 Hz), 7.43 (2 H, t, J = 7.5 Hz), 4.33–
4.05 (6 H, m), 3.63 (1 H, dd, J = 6.9, 9.3 Hz), 2.44 (1 H, m),
2.26–2.17 (2 H, m), 1.72 (1 H, m), 1.45 (3 H, s), 1.40 (3 H,
s), 1.37 (3 H, s). 13C NMR (75 MHz, CDCl3): d = 166.7 (s),
133.7 (d), 130.1 (s), 129.9 (d), 128.9 (d), 109.9 (s), 83.6 (d),
81.4 (s), 79.7 (d), 69.9 (t), 65.4 (t), 61.2 (d), 46.2 (d), 39.5
(d), 31.3 (t), 28.7 (q), 26.8 (q), 23.7 (q). MS (EI): m/z (%) =
426 (14) [M+], 424 (15) [M+], 411 (30), 409 (32), 351 (5),
349 (5), 329 (3), 287 (4), 229 (13), 227 (15), 183 (6), 165
(19), 147 (22), 105(100). HRMS: m/z calcd for
2.80–2.67 (2 H, m), 2.49–2.37 (1 H, m), 1.43 (3 H, s). 13
C
NMR (75 MHz, CDCl3): d = 208.0 (s), 166.4 (s), 133.5 (d),
129.8 (s), 129.7 (d), 128.7 (d), 82.2 (d), 76.6 (s), 69.5 (t),
64.4 (t), 59.9 (d), 43.5 (t), 41.3 (d), 36.6 (q), 22.5 (q). MS
(EI): m/z (%) = 303 (15), 285 (4), 274 (5), 257 (3), 189 (8),
181 (48), 163 (13), 153 (14), 138 (20), 121 (11), 105 (100),
95 (13), 77 (24). HRMS: m/z calcd for C17H19O5NaBr [M +
23]+: 405.0313; found: 405.0322.
Compound 23: colorless oil, mixture of a-bromoketones.
1H NMR (300 MHz, CDCl3): d = 8.05–8.01 (4 H, m), 7.58
(2 H, t, J = 7.5 Hz), 7.48–7.43 (4 H, m), 4.53–4.27 (8 H, m),
4.18 (1 H, dd, J = 7.8, 9.0 Hz), 3.97 (1 H, d, J = 10.2 Hz),
3.76–3.70 (2 H, m), 3.68 (3 H, s), 3.65 (3 H, s), 2.85–2.62
(4 H, m), 2.50–2.39 (2 H, m), 2.42 (3 H, s), 2.36 (3 H, s).
13C NMR (75 MHz, CDCl3): d = 200.9/200.2 (s), 172.4 (s),
166.7 (s), 133.6 (d), 130.0 (s), 130.0 (d), 128.9 (d), 80.4/80.0
(d), 70.9/70.4 (t), 65.7/65.6 (t), 54.5/49.3 (d), 52.4 (q), 44.6/
43.7 (d), 41.3/40.9 (d), 33.8/33.4 (t), 27.7/26.1 (q). MS (EI):
m/z (%) = 333 (25), 277 (20), 259 (6), 211 (30), 179 (15), 155
(35), 151 (29), 105(100). HRMS: m/z calcd for
C18H21O6NaBr [M + 23]+: 435.0419; found: 435.0421.
Compound 1 (R = Me): colorless oil, [a]D20 +58.8 (c 1.822,
acetone). 1H NMR (300 MHz, CDCl3): d = 8. 01 (2 H, d,
J = 7.2 Hz), 7.56 (1 H, t, J = 7.5 Hz), 7.43 (2 H, dd, J = 7.2,
7.5 Hz), 5.82 (1 H, s), 4.39 (1 H, dd, J = 6.0, 9.6 Hz), 4.32–
4.21 (3 H, m), 3.93 (1 H, dd, J = 3.0, 11.7 Hz), 3.67 (3 H, s),
2.93 (1 H, dd, J = 3.0, 16.5 Hz), 2.78 (1 H, q, J = 6.0 Hz),
2.48 (1 H, dd, J = 10.8, 16.5 Hz), 2.12 (3 H, s). 13C NMR (75
MHz, CDCl3): d = 197.3 (s), 177.5 (s), 172.2 (s), 166.7 (s),
133.6 (d), 130.1 (s), 130.0 (d), 128.8 (d), 99.7 (d), 72.4 (t),
65.8 (t), 52.3 (q), 42.6 (d), 42.1 (d), 35.6 (t), 31.7 (q). MS
(EI): m/z (%) = 333 (1) [M+ + 1], 290 (2), 259 (5), 247 (5),
210 (22), 193 (12), 137 (15), 105(100). HRMS: m/z calcd for
C18H20O6Na [M + 23]+: 355.1157; found: 355.1152.
Paeonilide: colorless needles; [a]D20 +50.6 (c 0.775,
acetone). Authentic sample: [a]D20 +53.5 (c 0.340, acetone).
IR (KBr): 3438 (s), 1763 (s), 1709 (s), 1281 (s), 1119 (s),
1041 (m), 949 (m), 922 (m), 717 (s) cm–1. 1H NMR (300
MHz, CDCl3): d = 8.01 (2 H, d, J = 7.5 Hz), 7.59 (1 H, t,
J = 7.5 Hz), 7.44 (2 H, t, J = 7.5 Hz), 4.29 (1 H, dd, J = 7.2,
11.1 Hz), 4.17 (1 H, dd, J = 8.1, 11.1 Hz), 4.02 (2 H, m), 3.41
(1 H, d, J = 17.8 Hz), 3.34 (1 H, dd, J = 10.5, 18.5 Hz),* 2.96
(1 H, d, J = 18.4 Hz), 2.94 (1 H, m), 2.54 (1 H, dd, J = 2.8,
18.4 Hz),* 2.54 (1 H, m), 2.19 (3 H, s). 13C NMR (75 MHz,
CDCl3): d = 204.5 (s), 174.6 (s), 166.5 (s), 133.6 (d), 129.8
(s), 129.7 (d), 128.7 (d), 115.1 (s), 68.1 (t), 65.1 (t), 49.7 (t),
46.9 (d), 44.5 (d), 36.8 (t), 31.1 (q). MS (EI): m/z (%) = 196
(15), 178 (9), 152 (52), 139 (12), 105(100), 94 (53). HRMS:
m/z calcd for C17H18O6Na [M + 23]+: 341.1001; found:
341.1001. *A few typing errors were found for the
C20H25O5NaBr [M + 23]+: 447.0783; found: 447.0774.
Compound 17: colorless oil; [a]D20 +23.4 (c 1.161, CHCl3).
IR (KBr): 3453 (br s), 2977 (s), 2940 (s), 2889 (s), 1719 (s),
1601 (w), 1451 (s), 1394 (s), 1376 (s), 1274 (s), 1117 (s),
1069 (s), 1026 (s), 756 (s), 713 (s) cm–1. 1H NMR (300 MHz,
CDCl3): d = 8.01 (2 H, d, J = 7.5 Hz), 7.57 (1 H, t, J = 7.5
Hz), 7.44 (2 H, t, J = 7.5 Hz), 4.43 (1 H, d, J = 7.5 Hz), 4.39
(1 H, dd, J = 5.7, 11.2 Hz), 4.29 (1 H, dd, J = 4.4, 6.7 Hz),
4.23 (1 H, d, J = 9.2 Hz), 4.21 (1 H, d, J = 9.3 Hz), 3.94 (1
H, t, J = 4.5 Hz), 3.73 (1 H, dd, J = 7.2, 9.0 Hz), 3.37 (1 H,
br s), 2.98 (1 H, m), 2.37 (1 H, m), 2.01–1.90 (2 H, m), 1.33
(3 H, s). 13C NMR (75 MHz, CDCl3): d = 166.5 (s), 133.2
(d), 129.8 (s), 129.6 (d), 128.4 (d), 82.5 (d), 74.2 (d), 72.3 (s),
69.6 (t), 65.2 (t), 42.5 (d), 39.6 (d), 28.2 (t), 22.8 (q), 14.2 (q).
MS (EI): m/z (%) = 323 (1), 305(3), 287 (30), 264 (10), 262
(11), 217 (7), 183 (13), 165 (86), 147 (36), 138 (26), 123
(26), 105 (100). HRMS: m/z calcd for C17H21O5NaBr [M +
23]+: 407.0470; found: 407.0463.
Compound 18: colorless oil. 1H NMR (300 MHz, CDCl3):
d = 9.82 (1 H, d, J = 1.5 Hz), 8.03 (2 H, d, J = 7.8 Hz), 7.58
(1 H, t, J = 7.9 Hz), 7.45 (2 H, t, J = 7.9 Hz), 4.82 (1 H, dd,
J = 6.3, 8.6 Hz), 4.31–4.20 (2 H, m), 4.00–3.86 (3 H, m),
3.25 (1 H, ddd, J = 3.0, 8.9, 9.0 Hz), 2.52–2.33 (3 H, m),
1.48 (3 H, s). 13C NMR (75 MHz, CDCl3): d = 200.4 (s),
166.8 (s), 133.6 (d), 130.2 (s), 130.0 (d), 128.9 (d), 90.4 (d),
82.1 (s), 70.5 (t), 65.3 (t), 65.0 (d), 62.1 (d), 45.1 (d), 44.2
(d), 24.6 (q).
assignment of protons at C13 position in the original paper
published in Biosci. Biotechnol. Biochem. (see ref. 2). It
should be corrected as 3.34 (1 H, dd, J = 10.5, 18.5 Hz) and
2.55 (1 H, dd, J = 2.8, 18.5 Hz).
Compound 22: colorless oil; [a]D20 +50.7 (c 0.725, CHCl3).
IR (KBr): 3442 (br s), 2949 (w), 2892 (w), 1721 (s), 1601
Synlett 2006, No. 7, 1051–1054 © Thieme Stuttgart · New York