Six new compounds from Atractylodes lancea and their hepatoprotective activities

Article abstract of DOI:10.1016/j.bmcl.2016.09.069

Two new phenolic glycosides with a rare β-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl moiety (1, 2), one new dihydrobenzofuran derivative (3), one new pyrazine derivative (4), two new furofuran lignan glycosides (5, 6), and six known compounds (7–12) were isolated from the rhizomes of Atractylodes lancea. The structures of these compounds were elucidated by extensive spectroscopic analyses combined with the experimental and calculated electronic circular dichroism and the Rh₂(OCOCF₃)₄-induced circular dichroism for configurational assignments. Notably, compounds 1–3 showed significant hepatoprotective activities against N-acetyl-p-aminophenol-induced HepG2 cell injury. This study is also the first Letter on the isolation of furofuran lignans and pyrazine derivatives (4–7) from the genus Atractylodes.

Full text of DOI:10.1016/j.bmcl.2016.09.069

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Accepted Manuscript
Six new compounds from Atractylodes lancea and their hepatoprotective ac-
tivities
Kuo Xu, Ya-Nan Yang, Zi-Ming Feng, Jian-Shuang Jiang, Pei-Cheng Zhang
PII:
S0960-894X(16)31018-6
DOI:
http://dx.doi.org/10.1016/j.bmcl.2016.09.069
BMCL 24293
Reference:
Bioorganic & Medicinal Chemistry Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
4 August 2016
23 September 2016
28 September 2016
Please cite this article as: Xu, K., Yang, Y-N., Feng, Z-M., Jiang, J-S., Zhang, P-C., Six new compounds from
Atractylodes lancea and their hepatoprotective activities, Bioorganic & Medicinal Chemistry Letters (2016), doi:
http://dx.doi.org/10.1016/j.bmcl.2016.09.069
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Six new compounds from Atractylodes lancea and
their hepatoprotective activities
Kuo Xu, Ya-Nan Yang, Zi-Ming Feng, Jian-Shuang Jiang, Pei-Cheng Zhang*
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of
Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences,
Beijing 100050, People's Republic of China
*Corresponding author. Tel: +86-10-63165231. Fax: +86-10-63017757. E-mail:
pczhang@imm.ac.cn
1

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
ABSTRACT
Two new phenolic glycosides with a rare β-D-glucopyranosyl-(1→3)-α-L-rhamnopyranosyl
moiety (1, 2), one new dihydrobenzofuran derivative (3), one new pyrazine derivative (4),
two new furofuran lignan glycosides (5, 6), and six known compounds (7−12) were isolated
from the rhizomes of Atractylodes lancea. The structures of these compounds were elucidated
by extensive spectroscopic analyses combined with the experimental and calculated electronic
circular dichroism and the Rh2(OCOCF3)4-induced circular dichroism for configurational
assignments. Notably, compounds 1−3 showed significant hepatoprotective activities against
N-acetyl-p-aminophenol-induced HepG2 cell injury. This study is also the first report on the
isolation of furofuran lignans and pyrazine derivatives (4−7) from the genus Atractylodes.
key words:
Atractylodes lancea
phenolic glycosides
furofuran lignan
pyrazine
dihydrobenzofuran
2

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Genus Atractylodes are distributed widely in eastern Asia and has a long medical history.
The rhizomes of Atractylodes lancea, known as 'Cangzhu' in traditional Chinese medicine,
were reputed to treat rheumatic diseases, digestive disorders, influenza, and other diseases.1−3
Previous phytochemical investigations revealed a series of sesquiterpenoids, monoterpenes,
polyacetylenes, phenolic acids, and steroids from A. lancea.4−9 A survey of the literature
revealed that the extract and chemical constituents of this plant possess potent
hepatoprotective effects.10 In our search for bioactive constituents from A. lancea,11 six new
compounds including two phenolic glycosides (1, 2),12,13 one prenylated dihydrobenzofuran
derivative (3),14 one pyrazine derivative (4),15 two furofuran-type lignan glycosides (5, 6),16,17
and six known compounds (7−12) were isolated from the n-butanol fraction. The structures of
these compounds were determined by extensive spectroscopic analyses. The stereochemistry
of 3−6 was defined using the experimental and calculated electronic circular dichroism (ECD)
and Rh2(OCOCF3)4-induced CD. All of the compounds were assessed for the hepatoprotective
activities against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell injury.18
Compound 1 has the molecular formula of C19H26O12 with seven degrees of unsaturation,
13
as deduced by the HRESIMS adduct ion at m/z 445.1353 [M − H]− and C NMR data. Its
IR spectrum showed absorption signals of hydroxy (3389 cm−1) and phenyl (1694, 1606,
and 1510 cm−1) groups. The four aromatic proton resonances (Table 1) at δH 7.14 (2H, d,
8.5 Hz) and 7.89 (2H, d, 8.5 Hz) in the 1H NMR spectrum, in association with the aromatic
carbon resonances (Table 1) at δC 116.2, 124.3, 131.3, 159.4, and 166.9 in the 13C NMR
spectrum suggested the p-hydroxybenzoic acid skeleton. The remaining 12 carbon signals
3