First total synthesis of the highly potent antitumor lactones 8-chlorogoniodiol and parvistone A: Exploiting a bioinspired late-stage epoxide ring-opening

Article abstract of DOI:10.1016/j.tetasy.2017.01.005

The first protecting group-free total syntheses of the highly potent antitumor chlorinated styryllactone secondary metabolites 8-chlorogoniodiol, parvistone A, and one analogue 8-epi-parvistone A, have been accomplished from commercially available trans-cinnamaldehyde in five steps with high overall yields. The chlorine-bearing stereogenic center of these silent secondary metabolites was introduced via a bioinspired late-stage regioselective epoxide ring-opening strategy. Maruoka asymmetric allylation, acrylation, ring-closing metathesis and asymmetric epoxidation, greatly facilitate the synthesis of the key intermediates goniothalamin oxide and (6S,7S,8S)-isogoniothalamin oxide.

Full text of DOI:10.1016/j.tetasy.2017.01.005

Tetrahedron: Asymmetry xxx (2017) xxx–xxx
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
First total synthesis of the highly potent antitumor lactones
8-chlorogoniodiol and parvistone A: Exploiting a bioinspired
late-stage epoxide ring-opening
a,b,
c
b
Perla Ramesh a, , Yarram Narasimha Reddy
, Thatikonda Narendar Reddy , Navuluri Srinivasu
⇑
⇑
a Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India
b Department of Science and Humanities, VFSTR University, Vadlamudi, Guntur 522213, India
c Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The first protecting group-free total syntheses of the highly potent antitumor chlorinated styryllactone
secondary metabolites 8-chlorogoniodiol, parvistone A, and one analogue 8-epi-parvistone A, have been
accomplished from commercially available trans-cinnamaldehyde in five steps with high overall yields.
The chlorine-bearing stereogenic center of these silent secondary metabolites was introduced via a bioin-
spired late-stage regioselective epoxide ring-opening strategy. Maruoka asymmetric allylation, acryla-
tion, ring-closing metathesis and asymmetric epoxidation, greatly facilitate the synthesis of the key
intermediates goniothalamin oxide and (6S,7S,8S)-isogoniothalamin oxide.
Received 11 November 2016
Revised 3 January 2017
Accepted 6 January 2017
Available online xxxx
Ó 2017 Elsevier Ltd. All rights reserved.
O
5
O
O
1. Introduction
2
3
4
R
8
1 O
6
Cl
O
Cl
O
10
13
More than 5000 halogen containing natural products have been
discovered from Nature in the past few decades.1 These halo-
genated natural products possess a broad range of biological activ-
ities of pharmacological interest, including antifungal, antitumor,
antibiotic, anti-inflammatory and antiviral activities.2 The presence
of halogen atoms in many bioactive molecules has a profound influ-
ence on their biological activity.3 A large number of drugs and drug
candidates in clinical development are halogenated compounds.
Some examples of halogenated natural products include the
remarkably potent anticancer agents salinosporamide A, spongis-
tatin, rebeccamycin, and calicheamicin, and a number of antibiotics,
such as vancomycin, chlortetracycline, and chloramphenicol.
8-Chlorogoniodiol 1a (Fig. 1) is the first styryllactone possessing
a chlorine atom, which was isolated from the aerial parts of
Goniothalamus amuyon by Yang-Chang Wu et al. in 2003.4 It was
also isolated from the same plant two years later by the same
group, and evaluated for the cytotoxicity against several tumor cell
lines.5 8-Chlorogoniodiol 1a showed highly potent cytotoxicity
against Human hepatocellular carcinoma (HepG2), Human
hepatoma cell line (Hep3B), Human breast cancer cell lines
(MDA-MB-231) and Human breast carcinoma (MCF-7) with IC50
9
7
11
12
OH
OH
parvistone A 2
OH
8-epi-parvistone A 3
14
1a
: R = Cl
8-chlorogoniodiol
(+)-goniodiol 1b: R = OH
Figure 1. Structures of goniodiol and chlorinated analogues.
values of 0.64, 3.64, 1.47 and 2.32
showed significant selective cytotoxicity against human gastric
cancer (HONE-1) cell line with an IC50 value of 4.87 .080 g/mL.
lg/mL respectively. It also
l
Parvistone A 2 is another new chlorinated styryllactone, very
recently isolated from the leaves of Polyalthia parviflora,6 a shrubby
tree found in different Asian countries including Thailand,
Malaysia, and Cambodia, which is found to possess cytotoxic activ-
ities against Hep G2, MDA-MB-231 and A549 cancer cell lines. In
addition, parvistone A 2 exhibits selective anti-inflammatory activ-
ity against superoxide anion with IC50 value of 30.0 2.5 l
M.6
The styryllactone’s activity was highly influenced by the
substituents at C-8, and showed the potency order as follows:
Cl > OCH3 > epoxide > OH. The 8-chlorogoniodiol 1a was 15-,
5- and 6-fold more potent than (+)-goniodiol 1b against HepG2,
Hep3B and MDA-MB-231 human cancer cell lines respectively.4,5
In the case of human breast carcinoma (MCF-7) cell lines,
⇑
Corresponding authors. Tel.: +91 40 27191631; fax: +91 40 27160512.
E-mail addresses: perlaramesh@yahoo.co.in (P. Ramesh), nyarram20@gmail.com
(Y. Narasimha Reddy).
http://dx.doi.org/10.1016/j.tetasy.2017.01.005
0957-4166/Ó 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Ramesh, P.; et al. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.01.005

2
P. Ramesh et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
O
8-chlorogoniodiol 1a (IC50 = 2.32
doxorubicin drug (DOX, IC50 = 2.51
l
g/mL) was more active than
regioselective
lg/mL). The structures and the
epoxide opening
O
O
absolute configurations of 8-chlorogoniodiol and parvistone A were
established by extensive 1D, 2D NMR spectroscopic analysis and
X-ray crystallographic data.4,6
Although numerous extensive synthetic endeavours have been
documented in the literature with regards to the total synthesis
of diverse styryllactones,7 the synthetic efforts toward highly
potent bioactive chlorinated styryllactones have not yet been
reported. Architecturally, 8-chlorogoniodiol and parvistone A are
d-lactones embedded with three contiguous stereogenic centers.
The presence of a chlorine-bearing stereogenic center at the
1a and 2
Ph
*
6
RCM
asymmetric
epoxidation
OH
*
Ph
O
Ph
7
8
Maruoka allylation
Scheme 2. Retrosynthetic analysis of 1a and 2.
active benzylic position, and an a,b-unsaturated d-lactone skeleton
made these molecules synthetically challenging. The highly potent
biological activities of 1a and 2, their natural scarcity and their
structural complexity of chlorine-bearing stereogenic center
prompted us to explore the total synthesis of 8-chlorogoniodiol
and parvistone A. In continuation of our syntheses of bioactive
natural products,8,9 we herein report the first total syntheses of
the 8-chlorogoniodiol 1a, parvistone A 2 and 8-epi-parvistone A 3
from inexpensive commercially available trans-cinnamaldehyde
using the modern concept of step economy, atom economy and
protecting group-free total synthesis.
Through investigating the structures of styryllactones, a plausi-
ble biosynthetic pathway was proposed by Chang et al.6
(Scheme 1). The condensation of cinnamoyl-CoA with two mole-
cules of malonyl-CoA followed by reduction, lactonization and
dehydration, provides lactone 4. Hydrogenation of 4 could provide
goniothalamin 5, which could be further oxidized at the benzylic
double bond to give the corresponding lactone epoxide 6. Epoxide
ring opening of 6 followed by chlorination in the presence of
haloperoxidase generates the chlorinated styryllactones 1a and 2.
The preparation of the key building blocks 6a and 6b was
achieved in a concise and scalable way from inexpensive commer-
cially available trans-cinnamaldehyde.9 The synthesis of goniotha-
lamin oxide 6a was envisaged by the Maruoka asymmetric
allylation10 of commercially available trans-cinnamaldehyde 7
with allyltributyltin, in the presence of (R)-BINOL, Ti(OiPr)4, and
Ag2O at À15 °C to give homoallylic alcohol (R)-8 in 94% yield and
with 94% ee. Alcohol (R)-8 was treated with acryloyl chloride in
the presence of triethylamine in CH2Cl2 to furnish the correspond-
ing acryloyl ester 9. Ring closing metathesis11 of the two terminal
double bonds in 9 was performed using a first generation Grubb’s
catalyst in CH2Cl2 at reflux to provide desired unsaturated lactone
(R)-5. Epoxidation of
a,b-unsaturated d-lactone (R)-5 with
m-chloroperoxybenzoic acid in CH2Cl2 at 0 °C yielded a 3:2 mixture
of diastereoisomers, with the desired epoxide lactone 6a as the
major isomer. The catalytic asymmetric epoxidation of (R)-5 under
Han’s reaction conditions12 with OxoneÒ in the presence of (S,S)-
salen–Mn(III) catalyst yielded the key intermediate goniothalamin
oxide 6a in 89% yield with a 98:2 diastereomeric ratio (Scheme 3).
O
O
O
O
2 malonyl CoA
TiCl4, Ti(OiPr)4
acryloyl chloride
Et3N, CH2Cl2
Ph
SCoA
Ph
SCoA
OH
(R)-BINOL, Ag2O
cinnamoyl CoA
Ph
O
O
Ph
0 oC, 2 h, 95%
allyltributyltin
CH2Cl2, -15 oC
48 h, 94%
7
8
(R)-
reduction
Ph
O
O
Ph
Ph
O
O
O
*
O
4
(S,S)-salen-Mn(III)
nBu4NHSO4
hexafluoroacetone
5
Grubbs-I
O
O
Cl
H
[O]
haloperoxidase
(Cl-)
O
CH2Cl2, reflux
6 h, 95%
O
H
Ph
buffer/CH3CN
Ph
9
Ph
O
O
Oxone, 0oC, 2 h 89%
*
*
5
(R)-
OH
1a and 2
6
O
O
Scheme 1. Plausible biogenetic pathway of 1a and 2.
Cl
O
O
HCl, Et2O
O
-60 oC, 1h, 95%
Ph
Ph
2. Results and discussion
6a
OH
8-chlorogoniodiol
1a
Lactones 1a and 2 contain three contiguous stereocenters and
display a clear structural similarity. The structural difference
between these two compounds lies in the configuration of the lac-
tone centre. Biosynthetically, the chlorinated styryllactones have
been proposed to originate from the lactone epoxide 6 precursor
through a regio and stereoselective epoxide ring opening. There-
fore, our retrosynthetic analysis of these natural products revealed
that the commercially available trans-cinnamaldehyde would be
an ideal starting material as outlined in Scheme 2. The asymmetric
allylation, asymmetric epoxidation, acrylation and ring-closing
metatheses are the key steps to secure the preparation of the key
intermediate lactone epoxide 6. Regioselective epoxide ring-open-
ing of 6 with chloride should complete the total synthesis of the
target chlorinated natural products.
Scheme 3. Synthesis of 8-chlorogoniodiol 1a.
At this stage, the introduction of the halogen-bearing stere-
ogenic center in a highly regio- and stereoselective manner via
SN2 opening of epoxide 6a with a chloride nucleophile was evalu-
ated. Initially, the substrate goniothalamin oxide 6a in Et2O was
treated with SOCl2 at 0 °C.13 After 1 h, an inseparable mixture of
8-chlorogoniodiol 1a and its C-8 epimer (dr. 8:2) was obtained in
95% yield. Further attempts to improve the diastereoselectivity by
switching the catalyst to chlorotrimethylsilane (TMSCl)14 in CHCl3
at 0 °C gave a similar result. When the hydrochloric acid in ether
was used at À60 °C, the reaction proceeded well to give an
improved diastereomeric ratio (>10:1) with 95% yield.14 At this
Please cite this article in press as: Ramesh, P.; et al. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.01.005

P. Ramesh et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
3
stage, the pure enantiomer of 8-chlorogoniodiol 1a15 was obtained
by recrystallization. The spectroscopic data of synthetic 1a matched
well with that reported for the natural product (Table 1). Moreover,
the corresponding epoxides to be obtained in a 1.5:1 mixture, with
the desired epoxide 10 as a minor isomer. The treatment of
epoxyalcohol 10 with acryloyl chloride gave the corresponding
acryloyl ester 11, which was then subjected to RCM using Grubbs’
first-generation catalyst in CH2Cl2 to furnish the desired (6S,7S,8S)-
isogoniothalamin oxide 6b in 92% yield. Similarly, intermediate 6b
was also obtained from d-lactone (S)-5 by (S,S)-salen–Mn(III) cat-
alyzed epoxidation with OxoneÒ as a 98:2 diastereomeric ratio in
90% yield. Finally, the ring-opening of oxirane 6b was achieved
with HCl in Et2O at À60 °C to obtain a mixture of diastereomers
2 and 3. These chlorinated lactones were efficiently separated by
flash column chromatography to give natural parvistone A 2 and
unnatural 8-epi-parvistone A 3 in 53 and 43% yields, respec-
tively.17–19 The spectroscopic data of synthetic 2 matched well
with that reported for the natural product (Table 2). Moreover,
the specific rotation value of synthetic 1a was [a]
25 = +13.1 (c 0.3,
D
CHCl3), which corresponded to the reported value [a]
25 = +13.7
D
(c 0.3, CHCl3)4 for the natural product.
Next, we turned our attention to the total synthesis of parvis-
tone A 2 (Scheme 4). The enantiomerically pure alcohol (S)-8
(94% ee) was prepared from the commercially available trans-cin-
namaldehyde using Maruoka asymmetric allylation reaction.
Sharpless asymmetric epoxidation16 of alcohol (S)-8 in the pres-
ence of (+)-diethyl tartrate, tert-butyl hydroperoxide, and Ti(OiPr)4
in CH2Cl2 provided the desired epoxyalcohol 10 as sole product.
However, the treatment of alcohol (S)-8 with m-chloroperbenzoic
acid (m-CPBA) performed at room temperature in DCM allowed
Table 1
Comparison of 1H and 13C NMR data of synthetic 1a and natural 8-chlorogoniodiol
1H NMR
13C NMR
H
Natural
Synthetic
(
D
d)N,S
C
Natural
Synthetic
(D
d)N,S
2
3
4
5
163.5
120.8
145.7
26.2
163.5
120.8
145.7
26.2
0.0
3
4
5
6.05 (dd, 9.8, 2.6)
6.98 (ddd, 9.8, 6.2, 2.0)
2.87 (ddt, 18.4, 12.8, 2.6)
2.32 (ddd, 18.4, 6.4, 4.0)
5.16 (dd, 12.8, 4.0)
3.96 (d, 9.0)
6.06 (ddd, 9.7, 3.6, 0.7)
6.99 (ddd, 9.7, 6.3, 2.0)
2.87 (m)
0.01
0.01
0.00
0.01
0.00
0.01
0.00
0.02
0.0
0.0
0.0
2.33 (m)
6
7
8
Ph
5.16 (ddd, 12.7, 3.7, 1.2)
3.97 (br t, 8.0)
5.12 (d, 9.7)
6
7
8
9
10
11
12
13
14
75.8
75.4
60.0
138.1
128.1
128.9
129.0
128.9
128.1
75.8
75.4
60.0
138.0
128.1
128.9
129.0
128.9
128.1
0.0
0.0
0.0
À0.1
0.0
0.0
0.0
0.0
0.0
5.12 (d, 9.0)
7.39 (m, 5H)
7.41 (m, 5H)
TiCl4, Ti(OiPr)4
(S)-BINOL, Ag2O
Ti(iPrO)4, (+)-DET
TBHP, DCM
OH
acryloyl chloride
OH
Et3N, CH2Cl2
Ph
O
O
O
Ph
4Å MS, -20 oC
12 h, 94%
allyltributyl tin, CH2Cl2
-15 oC, 48 h, 94%
0 oC, 2 h, 95%
7
Ph
(S)-8
10
O
O
O
Cl
Cl
O
O
Grubbs-I
HCl, Et2O
O
O
+
O
O
CH2Cl2, reflux
6 h, 92%
-60 oC, 1h
96%, dr. 55:45
Ph
Ph
Ph
Ph
11
OH
6b
OH
parvistone A 2
8-epi-parvistone A 3
Scheme 4. Synthesis of parvistone A 2 and 8-epi-parvistone A 3.
Table 2
Comparison of 1H and 13C NMR data of synthetic 2 and natural parvistone A
1H NMR
13C NMR
H
Natural
Synthetic
(D
d)N,S
C
Natural
Synthetic
(Dd)N,S
2
3
4
5
163.4
121.0
145.2
24.6
163.1
121.0
145.2
24.6
À0.3
0.0
0.0
3
4
5
6.02 (ddd, 10.4, 2.8, 1.2)
6.91 (ddd, 10.4, 5.8, 2.8)
2.54 (ddt, 19.7, 5.8, 1.2)
2.62 (ddt, 19.7, 10.8, 2.8)
4.36 (ddd, 10.8, 5.8, 4.0)
4.32 (ddd, 9.6, 5.6, 4.0)
5.13 (d, 5.6)
6.01 (ddd, 9.7, 2.7, 1.0)
6.91 (ddd, 9.7, 6.1, 2.5)
2.52 (ddt, 18.4, 6.1, 1.0)
2.61 (ddt, 18.4, 10.9, 2.5)
4.35 (ddd, 10.8, 6.4, 4.2)
4.32 (dt 5.4, 2.5)
À0.01
0.00
À0.02
À0.01
À0.01
0.00
0.0
6
7
8
Ph
6
7
8
9
10
11
12
13
14
77.2
75.5
62.1
136.4
128.5
128.6
129.0
128.6
128.5
77.2
75.5
62.1
136.4
128.5
128.6
129.0
128.6
128.5
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
5.13 (d, 5.4)
7.43 (m, 5H)
0.00
0.01
7.42 (m, 5H)
Please cite this article in press as: Ramesh, P.; et al. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.01.005

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P. Ramesh et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
25 = À114 (c 0.21,
6. Jing-Ru, L.; Tung-Ying, W.; Tran, D. T.; Tsong-Long, H.; Chin-Chun, W.; Yuan-
Bin, C.; Michael, Y. C.; Yu-Hsuan, L.; Mohamed, E.; Shwu-Li, W.; Ludger, B.;
Shyng-Shiou, Y.; Ming-Feng, H.; Shu-Li, C.; Fang-Rong, C.; Yang-Chang, W. J.
Nat. Prod. 2014, 77, 2626.
the specific rotation value of synthetic 2 was [a]
D
CH2Cl2), which corresponded to the reported value [
a]
22 = À124
D
(c 0.22, CH2Cl2)6 for the natural product.
7. (a) Mondon, M.; Gesson, J.-P. Curr. Org. Synth. 2006, 3, 41; (b) Prasad, K. R.;
Dhaware, M. G. Synlett 2007, 1112; (c) Yadav, J. S.; Madhavarao, B.; Sanjeeva
Rao, K. Synlett 2009, 3179.
3. Conclusion
8. (a) Ramesh, P.; Raju, A.; Fadnavis, N. W. Tetrahedron: Asymmetry 2015, 26,
1251; (b) Ramesh, P.; Raju, A.; Paramesh, J.; Ramisetti, A. Tetrahedron Lett. 2016,
57, 1087; (c) Ramesh, P.; Raju, A.; Fadnavis, N. W. Helv. Chim. Acta 2016, 99, 70.
9. (a) Ramesh, P.; Rao, T. P. J. Nat. Prod. 2016, 79, 2060; (b) Ramesh, P.
ChemistrySelect 2016, 1, 3244; (c) Ramesh, P. Synthesis 2016, 48, 4300.
10. (a) Hanawa, H.; Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc. 2003, 125, 1708;
(b) Hanawa, H.; Uraguchi, D.; Konishi, S.; Hashimoto, T.; Maruoka, K. Chem. Eur.
J. 2003, 9, 4405.
11. (a) Ramesh, P.; Anjibabu, R.; Raju, A. Tetrahedron Lett. 2016, 57, 2100; (b) Trnka,
T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18; (c) Grubbs, R. H.; Miller, S. J.;
Fu, G. C. Acc. Chem. Res. 1995, 28, 446; (d) Hoveyda, A. H.; Zhugralin, A. R.
Nature 2007, 450, 243; (e) Sabitha, G.; Rao, A. S.; Sandeep, A.; Latha, B. M.;
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Yadav, J. S. Tetrahedron: Asymmetry 2011, 22, 866.
In conclusion, we have disclosed a highly efficient stereoselec-
tive total synthesis of 8-chlorogoniodiol 1a, parvistone A 2 and
8-epi-parvistone A 3 for the first time. The key step in their total
syntheses is the bioinspired late-stage epoxide ring-opening reac-
tion. 8-Chlorogoniodiol 1a, parvistone A 2 and 8-epi-parvistone A 3
were synthesised in five linear steps from inexpensive commer-
cially available trans-cinnamaldehyde in excellent overall yields.
This concise and protecting group-free synthetic strategy provides
new insights in the potential synthesis of these halogenated sec-
ondary metabolites and offers opportunities to create analogues
for anticancer drug discovery.
12. Lim, J.; Kim, I.-H.; Kim, H. H.; Ahn, K.-S.; Han, H. Tetrahedron Lett. 2001, 42,
4001.
13. (a) Barluenga, S.; Moulin, E.; Lopez, P.; Winssinger, N. Chem. Eur. J. 2005, 11,
4935; (b) Taiki, U.; Masayuki, S.; Kensuke, K.; Tatsufumi, O.; Fuyuhiko, M. Org.
Lett. 2011, 13, 904.
Acknowledgments
14. Rima, S. A.; James, E. R.; Richard, M. S.; Sherri, L. A.; Joseph, H. K.; Richard, E. M.;
Jian, L.; Trimurtulu, G.; Gottumukkala, V. S.; Thomas, H. C. J. Med. Chem. 2003,
46, 2985.
15. Experimental procedure and analytical data for 8-chlorogoniodiol 1a: To a stirred
solution of goniothalamin oxide 9a (0.5 g, 2.31 mmol) in CH2Cl2 (50 mL) at
À60 °C was added 4 M HCl in Et2O (2.89 mL, 11.5 mmol), and the reaction
mixture was stirred for a further 1 h. The solvent was evaporated under
reduced pressure, and purified by flash column chromatography (hexane:
The author thanks Council of Scientific and Industrial Research,
Ministry of Science and Technology, New Delhi, India for funding
the project ORIGIN (CSC-0108).
A. Supplementary data
EtOAc, 6:4) to give 8-chlorogoniodiol 1a (554 mg, 95%, dr: >10:1). Pure 8-
25
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetasy.2017.01.
005.
chlorogoniodiol 1a (320 mg, 55%) was obtained by recrystallization. [
a
]
=
D
+13.1 (c 0.3, CHCl3), lit.4 25 = +13.7 (c 0.3, CHCl3). ESI MS: m/z 253 [M+H]+
[a]
D ,
275 [M+Na]+. HRMS-ESI: m/z [M+H]+ calcd for C13H14O3Cl: 253.06260; found:
253.06227.
16. (a) Katzuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974; (b) Sharpless,
K. B.; Woodward, S. S.; Finn, M. G. Pure Appl. Chem. 1983, 55, 1823.
17. Experimental procedure for parvistone A 2 and 8-epi-parvistone A 3: To a stirred
solution of (6S,7S,8S)-isogoniothalamin oxide 6b (0.5 g, 2.31 mmol) in CH2Cl2
(50 mL) at -60 °C was added 4 M HCl in Et2O (2.89 mL, 11.5 mmol), and the
reaction mixture was stirred for a further 1 h. The solvent was evaporated
under reduced pressure, and purified by flash column chromatography
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(hexane:EtOAc, 6:4) to give parvistone
A 2 (308 mg, 52.8%) and 8-epi-
parvistone A 3 (252 g, 43.2%).
18. Analytical data for parvistone A 2: [
a
]
D
25 = À114 (c 0.21, CH2Cl2), lit.6
[a
]
22 = À124
D
(c 0.22, CH2Cl2). ESI MS: m/z 253 [M+H]+, 275 [M+Na]+. HRMS-ESI: m/z [M+H]+
calcd for C13H14O3Cl: 253.06260; found: 253.06260.
19. Analytical data for 8-epi-parvistone A 3: [
a
]
25 = À33.2 (c 0.1, CHCl3). 1H NMR
D
(400 MHz, CDCl3): d = 7.49–7.33 (m, 5H), 6.92 (ddd, J = 9.7, 5.6, 2.8 Hz, 1H),
6.01 (dt, J = 9.7, 2.4 Hz, 1H), 5.39 (d, J = 3.3 Hz, 1H), 4.48 (ddd, J = 10.7, 7.2,
5.0 Hz, 1H), 4.10–4.05 (m, 1H), 2.59–2.47 (m, 2H) ppm. 13C NMR (CDCl3,
100 MHz): d = 163.1, 145.1, 137.8, 128.9, 128.8 (2C), 127.5 (2C), 121.1, 76.9,
75.8, 63.4, 25.3 ppm. ESI MS: m/z 253 [M+H]+, 275 [M+Na]+. HRMS-ESI: m/z [M
+H]+ calcd for C13H14O3Cl: 253.06260; found: 253.06261.
3. Constance, M. H.; Rajamoorthi, K.; Hana, K.; Thomas, M. H. J. Am. Chem. Soc.
1985, 107, 6652.
4. Lan, Y.-H.; Chang, F.-R.; Yu, J.-H.; Yang, Y.-L.; Chang, Y.-L.; Lee, S.-J.; Wu, Y.-C. J.
Nat. Prod. 2003, 66, 487.
5. Lan, Y.-H.; Chang, F.-R.; Liaw, C.-C.; Wu, C.-C.; Chiang, M.-Y.; Wu, Y.-C. Planta
Med. 2005, 71, 153.
Please cite this article in press as: Ramesh, P.; et al. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.01.005