Stereoselective synthesis of the styryllactones, 7-epi-goniodiol and leiocarpin A, isolated from Goniothalamus leiocarpus

Article abstract of DOI:10.1016/j.tetlet.2004.08.132

Two novel styryllactones, 7-epi-goniodiol and leiocarpin A, isolated from Goniothalamus leiocarpus, were stereoselectively synthesized in a short and efficient route from cinnamyl alcohol based on the asymmetric epoxidation and the palladium-catalyzed cross-coupling of vinyl epoxide with vinyltributylstannane.

Full text of DOI:10.1016/j.tetlet.2004.08.132

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8111–8113
Stereoselective synthesis of the styryllactones, 7-epi-goniodiol
and leiocarpin A, isolated from Goniothalamus leiocarpus
Jian Chen, Guo-Qiang Lin* and Han-Quan Liu
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, PR China
Received 9 August 2004; revised 16August 2004; accepted 20 August 2004
Available online 17 September 2004
Abstract—Two novel styryllactones, 7-epi-goniodiol and leiocarpin A, isolated from Goniothalamus leiocarpus, were stereoselectively
synthesized in a short and efficient route from cinnamyl alcohol based on the asymmetric epoxidation and the palladium-catalyzed
cross-coupling of vinyl epoxide with vinyltributylstannane.
Ó 2004 Elsevier Ltd. All rights reserved.
Styryl lactones are a series of natural products, exhibit-
ing moderate to significant biological activity including
antitumour and antifungal properties, as well as anti-
biotic potential. Up to now, more than twenty styryl lac-
tones have been isolated from plants and fungi.1,2
Because of their unique and intriguing structures as
well as their antitumour activities, much effort has been
centered on the development of methodology for the
synthesis of these substrates.3,4 Among them, leiocarpin
A and 7-epi-goniodiol are two new styryllactones,
recently isolated from the ethanolic extract of stem
barks of Goniothalamus leiocarpus (Annonaceae), a trop-
ical plant wide spread in the south of the Yunnan prov-
ince in China.5 7-epi-Goniodiol displayed selective
activities in test of trypan blue dye exclusion method,
and showed strong inhibition against HL-60 in concen-
tration as low as 1lg/mL. Their structures and relative
configurations were determined by NMR spectra studies
and X-ray crystallographic analysis. The structure as-
signed to 7-epi-goniodiol was similar to (+)-goniodiol
except for the configuration at the C7 chiral center.
The same structural relationship was found between
leiocarpin A and 9-deoxygoniopypyrone (Fig. 1).
by employing Sharpless asymmetric dihydroxylation as
the key step to secure the syn-configuration between
C6-OH and C7-OH in both structures. Because a trans-
configuration between C6-OH and C7-OH is the com-
mon feature between 7-epi-goniodiol and leiocarpin A,
we wish to describe herein a short and efficient synthetic
access to these compounds, by using an asymmetric
epoxidation followed by a intramolecular acid-catalyzed
ring-opening reaction as the key steps to control their
trans configuration.
Our synthesis began with the Sharpless epoxidation of
cinnamyl alcohol 1 to give 2 in high yield and high ee
(>98% ee).7 Swern oxidation of the resulting epoxide
2, followed by Wittig methylenation provided the vinyl
epoxide 3 in 74% yield over two steps without loss of
optical purity (Scheme 1).
As shown in our previous report that the palladium-cat-
alyzed cross-coupling of allylic cyclic carbonate 4 with
vinyltributylstannane 5 afforded the diene.6 We decided
to extend this approach to vinyl epoxide 3 (Scheme 2).
The reaction of 3 with 5 occurred under mild neutral
condition and provided diene 6 in higher yield and
stereoselectivity, however, with a little lower geometric
selectivity on the newly formed double bond. The results
are listed in Table 1.
In our previous paper,6 we described a facile synthetic
approach to (+)-goniodiol and 9-deoxygoniopypyrone,
Next, our attention was focused on the asymmetric
epoxidation of alcohol 6 and its C7-OH protected
compound 7 (Scheme 3). Three epoxidation conditions
were conducted, which led to leading to moderate
Keywords: Styryllactones; 7-epi-Goniodiol; Leiocarpin A; Synthesized;
Epoxidation.
*
Corresponding author. Tel.: +86 21 64163300; fax: +86 21
64166128; e-mail: lingq@pub.sioc.ac.cn
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.08.132

8112
J. Chen et al. / Tetrahedron Letters 45 (2004) 8111–8113
O
O
H
H
6
OH
7
O
6
H O
OH
7
O
6
H
O
O
7
O
O
7
6
O
OH
HO
H
OH
HO
H
9-Deoxygoniopypyrone
(+)-Goniodiol
7-epi-Goniodiol
Leiocarpin A
Figure 1.
O
O
a
OH
b
OH
1
2
3
Scheme 1. Reagents and conditions: (a) TBHP, Ti(OiPr)4, L-DIPT, 40 sieves, CH2Cl2, À15°C to 0°C, 90%y, 98%ee; (b), (1) 1.05equiv (COCl)2,
2equiv DMSO, Et3N, À78°C–rt, 89%, (2) t-BuOK, Ph3PCH3 I, THF, 0°C, 1h, 86%.
Table 2. Asymmetric epoxidation of 6, 7
O
Substrate
Conditions
Yield (%)
threo/erythro
O
O
OH
6
6
7
a
b
a
82
87
90
2.5:1
1:1.7
2.2:1
Bu3Sn
CO2Me
5
4
3
PdCl2(CH3CN)2
(5% mol)
DMF/H2O (4/1)
O
CO2Me
6
Scheme 2.
O
OH
O
OH
OH
Table 1. The Pd(0)-catalyzed reaction for substrates 3 and 4
a
Substrate
Yield (%)
ee (%)
E/Z
O
O
OH
CO2Me
8
4
3
71
83
95
>98
98.2:1.8
95:5
7-epi-Goniodiol
12
O
OH
O
diastereoselectivities, as shown in Table 2. The threo
epoxides 8 or 9 were obtained as major products when
m-CPBA was used, whereas the erythro epoxide 10
became the main product when using TBHP/VO(acac)2.
Fortunately, the two diastereomers can be completely
separated by flash column chromatography, however,
their diastereoselectivities remained moderate.
a
CO2Me
OH
10
6-epi-Goniodiol
O
O
13
H
OH
H
O
O
O
b
OH
HO
H
6-epi-Goniodiol
Leiocarpin A
13
Then, we intended to take advantage of the acid-cata-
lyzed epoxide ring opening reaction to control the
trans-configuration between C6 and C7 found in both
7-epi-goniodiol and leiocarpin A. Epoxide 8 was lacton-
ized by treatment of 30% HClO4 in methanol8 to give
7-epi-goniodiol 129 in 71% yield with inversion of the
configuration at C6. The same reaction converted epox-
ide 10 into 6-epi-goniodiol 13 in 74% yield. Finally,
reacting 6-epi-goniodiol led to leiocarpin A,10 another
natural product, through an intramolecular heteroatom-
Michael addition11 in 94% yield (Scheme 4).
Scheme 4. Reagents and conditions: (a) 30% HClO4 in MeOH, 0°C,
74% for 12, 71% for 13; (b) DBU, CH2Cl2, 0°C, 94%.
In summary, we have shown herein that the combina-
tion of the asymmetric epoxidation with the palla-
dium-catalyzed coupling of vinyl epoxide with
vinyltributylstannane opens an efficient and versatile
access to styryllactones such as 7-epi-goniodiol and
leiocarpin A.
OR
OR
O
OR
Oxidation
O
CO2Me
CO2Me
CO2Me
6, R=H,
7, R=TBS
10, R=H,
11, R=TBS
erythro
8, R=H,
9, R=TBS
threo
Scheme 3. Reagents and conditions: (a) m-CPBA (1.1equiv), NaHCO3, CH2Cl2, À20°C; (b) cat VO(acac)2, TBHP, (1.1equiv), CH2Cl2, À30°C.

J. Chen et al. / Tetrahedron Letters 45 (2004) 8111–8113
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Acknowledgements
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We acknowledge the financial assistance of The
National Natural Science Foundation of China. The
Major State Basic Research Development Program
(Grant No. 2000077506). We also thank Dr. Xin-Sheng
1
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20
20
9. For 7-epi-goniodiol: ½aꢀD +83.5 (c 0.4, MeOH), {lit. ½aꢀD
+85.4 (c 0.3, MeOH)}, IR (film): 3400, 2930, 1717, 1388,
1259, 1076; ESIMS m/z: 257.1 (M + Na); 1H NMR
(300MHz, C5D5 N); d 7.20–7.75 (m, 5H), 6.82 (ddd,
J = 9.5Hz, J = 5.9Hz, J = 2.9Hz), 5.95 (ddd, J = 9.5Hz,
J = 2.2Hz, J = 1.1Hz, 1H), 5.35 (d, J = 3.7Hz, 1H), 4.80–
5.80 (br s, 1H), 4.90 (dt, J = 10.8Hz, J = 5.4Hz, 1H), 4.30
(dd, J = 5.9Hz, J = 3.8Hz, 1H), 2.78 (m, 1H), 2.72 (m, 1H).
20
10. For leiocarpin A: ½aꢀD À97:6 (c 0.5, CHCl3) {lit.
20
½aꢀD À 98:42 (c 0.6, CHCl3)}, IR(KBr) mmax (cmÀ1):
3360, 1720, 1666, 1180; EIMS (m/z): 234 (60), 216
(M À 18, 7), 188 (10), 177 (17), 144 (15), 107 (100), 91
(40), 77 (43); HRMS for C13H14O4: found: 234.0890,
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(br s, 1H), 4.41 (d, J = 8.8, 1H), 3.45 (d, J = 8.8, 1H),
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