A New Synthetic Route Towards Picealactone a from an Abietic Acid

Article abstract of DOI:10.1007/s10600-017-2084-2

A new synthetic route towards picealactone A from an abietic acid, dehydroabietic acid, was introduced in this study. In this synthetic route, the picealactone A was synthesized by a tandem oxide/intramolecular esterification of 7-carbonyl dehydroabietic acid catalyzed by Yb(OTf)₃.

Full text of DOI:10.1007/s10600-017-2084-2

DOI 10.1007/s10600-017-2084-2
Chemistry of Natural Compounds, Vol. 53, No. 4, July, 2017
A NEW SYNTHETIC ROUTE TOWARDS PICEALACTONE A
FROM AN ABIETIC ACID
1
1,2*
3
1,2
Shengliang Liao, Minggui Shen,
Jie Song, Shibin Shang,
1
,2
1*
Xiaoping Rao, and Zhanqian Song
A new synthetic route towards picealactone A from an abietic acid, dehydroabietic acid, was introduced in
this study. In this synthetic route, the picealactone A was synthesized by a tandem oxide/intramolecular
esterification of 7-carbonyl dehydroabietic acid catalyzed by Yb(OTf)3.
Keywords: synthesis, picealactone A, dehydroabietic acid, Yb(OTf)3.
Dehydroabietic acid (DHAA) (1), a naturally occurring diterpene resin acid, has received increased interest in recent
years because it and its derivatives exhibit a variety of biological activities [1–5]. These features make DHAA a new scaffold
in drug design, and further chemical modifications of DHAA have important implications in drug development.
Chemical modifications on ring B of DHAA have been widely reported [6–8]. Previous research showed that some
derivatives synthesized by the modification of ring B exhibited potential pharmaceutical activity [7–9]. Hence, studies of new
derivatives of DHAA as pharmaceutical agents by structural changes on ring B of DHAA are meaningful and desired.
Picealactone is a valuable natural compound with many potential biological activities; it includes three types,
picealactone A, B, and C [10]. Among them, picealactone A can be synthesized through modification of ring B of DHAA [11,
1
2]. However, the existing synthetic method for picealactone A is not satisfactory because of low yield. Therefore, the present
work reports a new synthetic route toward picealactone A by modification of ring B of DHAA, which is achieved by a tandem
oxide/intramolecular esterification of 7-carbonyl dehydroabietic acid (Scheme 1).
Dehydroabietic acid (DHAA, 1) was isolated from disproportionated rosin according to the literature [13].
7
-Carbonyl DHAA (2) was obtained by oxidation of DHAA (1) according to the literature [14]. With 7-carbonyl DHAA(2) as
the raw material, we propose a method to prepare a dicarbonyl derivative of DHAA (or its enol tautomer) based on the
oxidation of 8-carbon to 8-carbonyl, then synthesize the lactone derivative of DHAA through intermolecular esterification.
SeO is believed to be an efficient oxidant for the transformation of the 8-carbon to 8-carbonyl, and Yb(OTf) is
2
3
regarded as an ideal catalyst for promoting this reaction; meanwhile, Yb(OTf) is a Lewis acid, which can be used to catalyze
3
the esterification reaction [15]. Accordingly, in this work, the 7-carbonyl DHAA (2) was treated with 2 eq of SeO and 0.1 eq
2
of Yb(OTf) in a dioxane–H O mixture so as to obtained a lactone derivative of DHAA.
3
2
As was expected, the tandem oxidation/intramolecular esterification proceeded successfully. Firstly, 7-carbonyl DHAA
(
2) was oxidized to 7,8-dicarbonyl DHAA (2a), but the reaction did not stop, since 7,8-dicarbonyl DHAA could transform to
an enol tautomer (2b), and subsequently intramolecular esterification occurred, catalyzed by the Yb(OTf) , to yield the lactone
3
1
compound picealactone A (3). The product picealactone A was characterized by mp, ESI-MS, and H NMR spectroscopy.
1
) Institute of Chemical Industry of Forest Products, China Academy of Forestry; National Engineering Laboratory
for Biomass Chemical Utilization; State ForestryAdministrationꢀs Key and Open Laboratory for Forest Chemical Engineering;
Jiangsu Provincial Key Laboratory for Biomass Energy and Material, 210042, Nanjing, Jiangsu, P. R. China, e-mail:
shenminggui@sina.com; lhssxly@hotmail.com; 2) Institute of New Technology of Forestry, China Academy of Forestry,
1
00091, Beijing, P. R. China; 3) Department of Chemistry and Biochemistry, University of Michigan-Flint, 303E Kearsley
Street, Flint, MI 48502, USA. Published in Khimiya Prirodnykh Soedinenii, No. 4, July–August, 2017, pp. 560–561.
Original article submitted October 31, 2015.
0
658
0009-3130/17/5304-0658 2017 Springer Science+Business Media New York

a
b
c
7
7
8
O
O
O
O
8
H
2
1
H
CO H
2
H
O
OH
CO H
O
CO
H
CO H
2
2
O
2
2a
a. CrO ; b. SeO , Yb(OTf) ; c. Yb(OTf)
3
2b
3
3
2
3
Scheme 1. Yb(OTf) catalyzed tandem oxide/intramolecular esterification of 7-carbonyl DHAA.
3
Since picealactone A is a known compound, the characterization data, including mp, HR-EI-MS, and H and 13C NMR has
1
been reported in the literature [10]. In this work, the tested mp of picealactone A is 182–186ꢁC. The ESI-MS signal at 311
+
[
M + H] indicates that the molecular weight of picealactoneAis 310. Consequently, the characterization data of picealactone
A obtained in this work are in good agreement with the reported data. This study can provide an alternative synthetic method
to picealactone A.
EXPERIMENTAL
1
All reagents were obtained from local commercial suppliers and used without further purification. H NMR spectra
TM
was recorded with a Bruker Ascend 400 analyzer in DMSO-d with TMS as internal standard. Mass spectra were recorded
6
on an Agilent-5973 spectrometer (ESI source).
Synthesis of 7-Carbonyl DHAA (2). A mixture of dehydroabietic acid (10 mmol), CrO (30 mmol), and AcOH
3
(
(
10 mL) was stirred at room temperature. After 3 h, the mixture was quenched into water (30 mL) and extracted with EtOAc
10 mL ꢂ 3). The organic phase was combined and washed with saturated NaCl solution (10 mL ꢂ 3), and then the
organic phase was dried, concentrated under vacuum, and purified by silica gel chromatography to afford the desired
1
product 7-carbonyl dehydroabietic acid. Sticky liquid. Yield 71%. H NMR (400 MHz, DMSO-d , ꢃ, ppm, J/Hz): 12.32
6
(
1H, s), 7.71 (1H, d, J = 1.8), 7.51 (1H, dd, J = 8.2, 1.9), 7.41 (1H, d, J = 8.2), 2.93 (1H, dd, J = 13.8, 6.9), 2.81 (1H, dd,
J = 17.6, 14.3), 2.49 (1H, d, J = 3.0), 2.39 (1H, d, J = 12.8), 2.19 (1H, dd, J = 17.6, 3.0), 1.92 (1H, s), 1.70 (3H, dd, J = 20.0,
+
1
3.0), 1.47 (1H, d, J = 12.8), 1.21 (9H, dd, J = 13.2, 7.0). ESI-MS m/z 315 [M + H] .
Synthesis of Picealactone A (3). A mixture of Yb(OTf) (0.1 mmol), 7-carbonyl dehydroabietic acid (10 mmol),
3
1
,4-dioxane (3 mL), H O (1 mL), and SeO (20 mmol) was stirred at 90ꢁC for 24 h. Then the mixture was cooled to room
2
2
temperature and filtered on a short pad of Celite in order to immobilize the unreacted SeO . The filtrate was extracted with
2
EtOAc (10 mL ꢂ 3). The organic phase was combined and washed with saturated NaCl solution (10 mL ꢂ 3), and then the
organic phase was dried, concentrated under vacuum, and purified by silica gel chromatography to afford the desired product.
2
0
1
White crystals, yield 78%, mp 182–186ꢁC. [ꢄ] +14.6ꢁ (c 0.5, CH OH). H NMR (400 MHz, DMSO-d , ꢃ, ppm, J/Hz): 7.96
D
3
6
(
1H, d, J = 1.9), 7.75 (1H, d, J = 8.2), 7.63 (1H, dd, J = 8.2, 2.0), 3.10–2.89 (1H, m), 2.43 (1H, d, J = 12.8), 2.09 (1H, d,
+
J = 14.1), 1.95 (1H, d, J = 12.6), 1.72 (2H, d, J = 14.7), 1.57 (6H, d, J = 8.0), 1.24 (6H, d, J = 6.9). ESI-MS m/z 311 [M + H] .
ACKNOWLEDGMENT
This work was supported by the National Natural Science Foundation of China under Grant U1202265; National
Natural Science Foundation of China under Grant 31500487; International Science and technology cooperation under Grant
2
014DFR31300.
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