Observation of 1,3-diketones formation in the reaction of bulky acyl chlorides with methyllithium

Article abstract of DOI:10.3390/molecules17066424

The formation of 1,3-diketones was observed in the reactions of bulky acyl chlorides with methyllithium. The reaction products depend on the steric hindrance around the carbonyl group of the acyl chloride and the electronic effect of the group(s) linked to the carbonyl. When the steric hindrance around the carbonyl group of the acyl chloride is big enough, the 1,3-diketone is the only product. In the case of the moderate hindrance around the carbonyl group of the acyl chloride, a moderate yield of 1,3-diketone is obtained and some tertiary alcohol is generated. When there is no steric hindrance around the carbonyl group of the acyl chloride, the tertiary alcohol is the only product. When the steric hindrance around the carbonyl group is moderate and an electron-donating group is connected to the carbonyl of the acyl chloride, all three products-ketone, 1,3-diketone and tertiary alcohol-can be isolated from the reaction mixture after long reaction times.

Full text of DOI:10.3390/molecules17066424

Molecules 2012, 17, 6424-6433; doi:10.3390/molecules17066424
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Two New Diterpenoids from the Buds of
Wikstroemia chamaedaphne
Jieru Guo 1, Jinwen Zhang 2, Penghua Shu 1, Lingmei Kong 3, Xincai Hao 1, Yongbo Xue 1,
Zengwei Luo 1, Yan Li 3, Gao Li 1, Guangmin Yao 1,* and Yonghui Zhang 1,*
1
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation,
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology,
Wuhan 430030, China
2
Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology,
Wuhan 430030, China
3
State Key Laboratory of Phytochemistry and Plant Resources in West China,
Kunming Institute of Botany, Chinese Academy of Science, Kunming 650204, China
* Authors to whom correspondence should be addressed; E-Mails: gyap@mail.hust.edu.cn (G.Y.);
zhangyh@mails.tjmu.edu.cn (Y.Z.); Tel.: +86-27-8369-2311; Fax: +86-27-8369-2762.
Received: 18 April 2012; in revised form: 15 May 2012 / Accepted: 22 May 2012 /
Published: 29 May 2012
Abstract: Two new diterpenoids, wikstroelide Q (1) and prostratin Q (5), together with
three known diterpenoids, pimelea factors P2 (2), P3 (3), and prostratin (4), and five
known lignans, (+)-epipioresinol (6), (+)-isolariciresinol (7), (−)-lariciresinol (8),
(+)-epi-sesaminone (9), and prestegane B (10), were isolated from the buds of
Wikstroemia chamaedaphne Meissn. Their structures were elucidated by a combination of
spectroscopic analyses. Compounds 1–10 were evaluated for their cytotoxicities against
HL-60, SMMC-7721, A549, MCF-7, SW480, and BEAS-2B cell lines in vitro.
Keywords: Wikstroemia chamaedaphne; diterpenoids; lignans; cytotoxicity
1. Introduction
Wikstroemia chamaedaphne Meissn. (Thymelaeaceae), a toxic shrub endemic to China that has
been used in folk medicine to treat edema, cough, hepatitis, schizophrenia, and antifertility [1,2].
Several flavonoids and the antifertile daphnane diterpenoid simplexin have been isolated from this

Molecules 2012, 17
6425
medicinal plant in previous phytochemical investigations [2,3]. In the course of a search for novel
anticancer natural products from Traditional Chinese Medicine, the acetone extract of the buds of
W. chamaedaphne showed potential in vitro cytotoxic activities against HL-60, SMMC-7721, A549,
MCF-7, and SW480 cell lines. Bioassay-guided isolation resulted in two new (compounds 1 and 5)
and three known diterpenoids 2–4, along with five known lignans 6–10. In this paper, we would like to
report the isolation and structure elucidation of two new diterpenoids, named wikstroelide Q (1) and
prostratin Q (5), and the cytotoxic activities of compounds 1–10 (Figure 1).
Figure 1. Structures of compounds 1–10.
2. Results and Discussion
The acetone extract of the air-dried buds of W. chamaedaphne was partitioned successively with
petroleum, CHCl3, and H2O as described in the Experimental. After repeated column chromatography,
two new compounds 1 and 5 and three known diterpenoids 2–4, together with five known lignans 6–10,
were isolated and identified. The known compounds were identified as pimelea factors P2 (2) [4,5],

Molecules 2012, 17
6426
P3 (3) [5,6], prostratin (4) [7], (+)-epipioresinol (6) [8], (+)-isolariciresinol (7) [8], (−)-lariciresinol (8) [9],
(+)-episesaminone (9) [10], and prestegane B (10) [11], respectively, on the basis of detailed MS and NMR
spectroscopic analysis and comparison with those reported data in the literature.
Wikstroelide Q (1) was isolated as a white amorphous powder, []2D0.0 +20.00 (c 0.22, MeOH). Its
molecular formula C39H52O9 was assigned by the positive HRESIMS data (m/z 687.3486 [M+Na]+,
calcd for C39H52O9Na, 687.3504), requiring 14 degrees of unsaturation. Its IR absorptions revealed the
presence of hydroxyls (3441 cm−1), carbonyl (1713 cm−1), double bond (1637 cm−1), and benzene ring
1
(1604 cm−1). The H-NMR spectrum of 1 (Table 1) showed signals for four methyl groups at δH 1.75
(3H, s), 1.25 (3H, d, J = 7.0 Hz), 1.04 (3H, d, J = 6.6 Hz), and 0.89 (3H, d, J =7.3 Hz), seven protons
attached to oxygenated carbons at δH 4.93 (1H, d, J = 11.9 Hz), 4.23 (1H, d, J = 2.4 Hz), 3.90 (1H, d,
J = 11.9 Hz), 3.79 (1H, d, J = 2.0 Hz), 3.73 (1H, br s), 3.30 (1H, s), and 3.01 (1H, d, J = 2.4 Hz), two
olefinic protons at δH 7.72 (1H, d, J = 16.0 Hz) and 6.52 (1H, d, J = 16.0 Hz), and a mono-substituted
13
benzene ring at δH 7.52 (2H, m) and 7.37 (3H, m). The C-NMR, DEPT, and HSQC spectra for 1
displayed thirty nine carbon signals differentiated as four methyls, ten methylenes (including one
oxygenated and one olefinic), seventeen methines (including seven olefins, four oxygenated), and eight
quaternary carbons (including one carbonyl, one olefin, and four oxygenated).
Figure 2. Key HMBC, 1H-1H COSY and NOESY of compound 1.
1'
1'
3'
3'
16
15
16
15
5'
5'
O
O
17
12
H
17
18
O
7'
18
O
13
7'
13
H3C
11
11
H
O
O
H
14
H
H
10'
9'
9'
H3C
H
8
9
8
10
4
10'
H
10
1
1
H3C
19
OH
7
7
2
2
H
6
3
O
O
O
3
19
5
5
O
H
9''
6''
OH
HO
3''
HO
OH
OH
20
H
20
O
1''
O
8''
7''
4''
2''
5''
HMBC (H C), 1H-1H COSY ( ), and NOESY (
)
The NMR data of 1 were quite similar to those of pimelea factor P3 (3) [5,6], a 1α-alkyldaphnane-
type diterpenoid orthoester with a ten-carbon side chain, with the exception of the additional signals
for one double bond (δH 6.52, d, J = 16.0 Hz, H-2′′; δH 7.72 d, J = 16.0 Hz, H-3′′; δC 117.9, C-2′′;
δC 145.8, C-3′′) in the downfield region of the spectra. In the HMBC spectrum, the cross peaks of these
two newly olefinic protons H-2′′ and H-3′′ to the conjugated carbonyl C-1′′ (δC 167.5) and the aromatic
carbon C-4′′ (δC 135.3) of the mono-substituted benzene ring, as well as the aromatic protons H-5′′/H-9′′of
the mono-substituted benzene ring to the newly olefinic carbon C-3′′, revealed that this additional double
bond was fixed between the carbonyl and the benzene ring, and suggested the presence of a cinnamoyl
group in 1. The larger coupling constants JH-2′′, H-3′′ = 16.0 Hz of H-2′′ and H-3′′ indicated the E-geometry
of the double bond in the cinnamoyl group, and the cinnamoyl group is the trans-cinnamoyl group.

Molecules 2012, 17
6427
1
13
Table 1. H-NMR (400 MHz) and C-NMR (100 MHz) Spectral Data of Compounds 1
and 5 in CDCl3 (δ in ppm, J in Hz).
1
5
No.
δH
δC
δH
7.57 s
δC
161.0
133.1
209.1
74.0
1β
2α
3α
4
5α
5β
6
7β
8β
9
10α
11
12a
12b
13
14
15
16a
16b
17
18
19
20a
20b
1′
2.02 dd (12.4, 11.8)
1.57 m
49.3
37.9
79.5
78.9
71.0
3.79 d (2.0)
3.73 br s
2.53 d (19.0)
2.46 d (19.0)
38.9
60.2
64.4
37.0
81.4
48.8
35.8
36.6
140.7
129.5
39.3
78.4
56.4
43.4
76.8
3.30 s
3.01 d (2.4)
5.66 d (4.5)
3.22 dd (4.5, 5.1)
2.77 d (12.4)
2.36 m
2.17 dd (8.4, 13.9)
1.66 d (13.9)
3.23 s
2.15 m overlap
5.44 d (10.3)
84.1
82.1
147.0
111.2
66.0
36.6
26.0
17.0
4.23 d (2.4)
1.08 d (5.1)
1.24s
4.97 s
4.86 s
1.75 s
1.25 d (7.0)
1.04 d (6.6)
4.93 d (11.9)
3.90 d (11.9)
19.1
21.3
14.8
68.1
1.19 s
24.0
14.6
10.3
68.3
0.87 d (6.6)
1.75 d (1.5)
4.02 d (13.0)
3.97 d (13.0)
120.0
33.9
19.7
167.3
119.1
145.8
2′
3′
1.89 m
1.53 m
1.66 m
1.22 m
1.23 m
1.30 m
1.53 m
1.39 m
1.30 m
0.94 m
2.32 m
0.89 d (7.3)
5.76 d (15.4)
7.21 dd (15.4, 9.8)
4′
5′
6′
7′
27.8
24.2
24.7
24.3
6.16 dd (9.8, 15.2)
6.13 m
2.13 m overlap
1.41 m
128.5
145.5
33.2
28.6
8′
24.5
1.28 m
31.6
9′
10′
1′′
2′′
3′′
4′′
5′′
27.3
19.1
1.28 m
0.86 t (6.9)
22.7
14.2
174.0
21.3
167.3
117.9
145.8
134.6
128.4
6.52 d (16.0)
7.72 d (16.0)
2.08 s
7.52 m

Molecules 2012, 17
6428
Table 1. Cont.
No.
1
5
δH
δC
δH
δC
6′′
7′′
8′′
9′′
7.37 m
129.1
130.7
129.1
128.4
7.37 m
7.37 m
7.52 m
The HMBC correlation of H-20 (δH 4.93, d, J = 11.9 Hz, H-20a; δH 3.90, d, J = 11.9 Hz, H-20b) to
the carbonyl C-1′′ of the trans-cinnamoyl group suggested the trans-cinnamoyl group was connected
1
to 20-OH. HSQC, H–1H COSY, and HMBC analysis (Figure 2) allowed us to construct the planar
structure of compound 1. The relative configuration of compound 1 was determined by the coupling
constants and the NOESY analysis (Figure 2). Similar to pimelea factor P3 (3) and other C30 1α-
alkyldaphnane-type diterpenoid orthoesters, the linkage between the penta-/sept- and sept-/hexa- rings
in compound 1 are trans, and H-10 was randomly assigned in an α-orientation. The larger coupling
constant J = 12.4 Hz of H-10α with H-1 indicated a trans-relationship between H-10α and H-1, and
H-1was in a β-orientation, consequently, C-1 side chain had an α-orientation. The NOESY correlations
of H-10α to H-2 and H-5 and H-2 to H-3 revealed that H-2 H-3, and H-5 were α-oriented. The singlet
peak of H-7 and the smaller coupling constants J = 2.4 Hz of H-8 with H-14 revealed the
syn-relationships of H-7, H-8, and H-14. The NOESY correlations of H-7/H-8, H-7/H-20b, H-8/H-11,
and H-8/H-14 indicated that H-7, H-8, H-11, H-14 and H-20b were assigned in β-orientations. A
literature survey revealed that when the absolute configuration of C-9′ was R, correspondingly,
10′-CH3 was in the α-orientation of the molecule, the chemical shift of C-10′ would appear around δC
19.0 [12,13]; if the C-9′ was S configuration, the C-10′ would shift downfield to δC 12.3 [4,5,13]. The
chemical shift of C-10′ δC 19.1 in 1 suggested the R configuration of C-9′ in 1. The NOESY
correlations of CH3-10′ with CH3-19, H-1 and H-2, H-9′ with CH3-18 and H-1, and H-8′ with H-10,
further supported the C-9′R configuration. Therefore, the structure of 1 was assigned as depicted. The
trans-cinnamoyl group is very common in phenolic compounds, however, it was very rare in
diterpenoids. To the best of our knowledge, compound 1 is the first example of C30 1α-alkyldaphnane-
type diterpenoid orthoester bearing a trans-cinnamoyl group.
Prostratin Q (5) was isolated as colorless gum, []2D0.0 +16.36 (c 0.03, MeOH), and exhibited an
quasi-molecular ion peak at m/z 579.2937 [M+Na]+ (calcd for C32H44O8Na, 579.2928), corresponding
to the molecular formula C32H44O8. Its IR absorptions indicated the presence of hydroxyls
(3420 cm−1), carbonyl (1714 cm−1), and double bond (1641 cm−1). The NMR spectral data (Table 1) of
5 were very similar to those of prostratin (4) [7], a phorbol-type diterpenoid isolated as a major
compound in this study, except for an additional long chain aliphatic ester of C10H15O2. The NMR data
of 5 indicated that the ester chain contained four olefinic protons at δH 5.76 (1H, d, J = 15.4 Hz, H-2′),
6.13 (1H, m, H-5′), 6.16 (1H, dd, J = 9.8, 15.2 Hz, H-4′), and 7.21 (1H, dd, = 15.4, 9.8 Hz, H-3′), with
corresponding carbons at δC 119.1, 145.5, 128.5, 145.8, respectively. The 1H-1H COSY correlations of
H-2′ to H-3′ (δH 7.21), H-3′ to H-4′, and H-4′ to H-5′, as well as HMBC correlations of H-2′ (δH 5.76)
and H-3′ (δH 7.21) to the ester carbonyl C-1′ (δC 167.3) demonstrated that the ester carbonyl C-1′
and these two double bonds were conjugated. Additionally, the geometry of the Δ2′ and Δ4′ olefins in 5

Molecules 2012, 17
6429
was established as Z on the basis of the larger (J
= 15.4 Hz, J
= 15.2 Hz) coupling
H-4′, H-5′
H-2′, H-3′
constants of H-2′ and H-4′. The HMBC correlation of H-12 (δH 5.44) to C-1′ (δC 167.3) indicated the
ester chain was located at C-12 of the phorbol skeleton. The relative configurations of 5 were identical
with those of prostratin (4), based on the detailed comparison of their coupling constants and the
NOESY analysis. The larger coupling constants JH-11, H-12 = 10.3 Hz of H-12 and the significant
NOSEY correlation between H-12 and CH3-18 permitted the assignment of ester chain substituent in
the β-configuration.
Compounds 1–10 were evaluated for their cytotoxic activities against five human cancer cell lines,
HL-60 (human myeloid leukemia), SMMC-7721 (hepatocellular carcinoma), A549 (lung cancer),
MCF-7 (breast cancer), and SW480 (colon cancer), and one human normal cell line BEAS-2B (human
bronchial epithelial) by the MTT method [14]. DDP (cis-platin) and taxol were used as positive controls.
Table 2. IC50 Values (μM) of Compounds 1–10 against Five Human Cancer Cell Lines and
One Human Normal Cell line.
Compounds
HL-60
26.43
13.81
13.29
15.57
15.79
>40
SMMC-7721
>40
A-549
>40
MCF-7
>40
SW480
>40
BEAS-2B
>40
1
2
3
4
5
6
17.51
14.93
18.09
15.12
>40
12.06
11.10
12.57
15.75
>40
12.78
13.98
15.97
14.96
>40
15.93
14.44
13.30
14.79
>40
17.35
15.43
17.38
16.55
>40
7
>40
>40
>40
>40
>40
>40
8
>40
>40
>40
>40
>40
>40
9
10
>40
>40
>40
>40
>40
>40
>40
>40
>40
>40
>40
>40
DDP (cis-platin)
Taxol
1.25
<0.008
16.18
<0.008
14.05
<0.008
16.95
<0.008
18.05
<0.008
8.61
5.00
The bioassay results (Table 2) revealed that compound 1 exhibited weak cytotoxic activity against
HL-60 cell lines with IC50 values of 26.43 μM, but was inactive against the SMMC-7721, A-549,
MCF-7, SW480, and BEAS-2B cell lines (IC50 > 40 μM). Compounds 2–4 showed moderate cytotoxic
activities [15] against the five human cancer cell lines and the human normal cell BEAS-2Bwithin
the IC50 value range of 13–18 μM. Compounds 5–10 were inactive against the cancer cells used
(IC50 > 40 μM).
3. Experimental
3.1. General Procedures
Optical rotations were measured on a PerkinElmer PE-341LC polarimeter. IR spectra were recorded
as KBr disks on a Bruker Vertex 70 FT-IR spectrophotometer. NMR spectra were recorded on a
1
Bruker AM-400 spectrometer, and the H- and 13C-NMR chemical shifts were referenced to the
solvent peaks for CDCl3 at δH 7.24 and δC 77.23. HRESIMS data were measured using an API QSTAR
Pulsar spectrometer. Column chromatography was performed using silica gel (200–300 mesh, Qingdao

Molecules 2012, 17
6430
Marine Chemical Inc., China), Amberchrom CG161M (75 μm, Rohm and Haas, USA), ODS (50 μm,
YMC, Japan), and Sephadex LH-20 (Pharmacia Biotech AB, Sweden). HPLC separation was
performed on an instrument consisting of an Agilent 1100 controller, an Agilent 1100 pump, and an
Agilent UV detector with an YMC (250 × 10 mm, 5 μm) preparative column. TLC was carried out on
precoated silica gel GF254 plates. Spots were visualized under UV light (254 or 356 nm) or by spraying
with 5% H2SO4 in 95% EtOH followed by heating.
3.2. Plant Material
The buds of W. chamaedaphne were collected from Ankang City in Shaanxi Province, China, in
July 2010, and authenticated by Prof. Changgong Zhang at School of Pharmacy, Tongji Medical
College, Huazhong University of Technology and Science. The voucher specimen (No. TJ-1002) was
deposited in the herbarium of Hubei Key Laboratory of Natural Medicinal Chemistry and Resource
Evaluation, Tongji Medical College, Huazhong University of Technology and Science.
3.3. Extraction and Isolation
The air-dried buds of W. chamaedaphne (40 kg) were extracted three times with acetone at room
temperature (100 L each time, seven days). The combined acetone extracts were concentrated to yield
a dry residue (1.9 Kg). This crude extract was suspended in H2O (4.0 L) and partitioned successively
with petroleum ether (60–90 °C) and chloroform. The chloroform fraction (180 g) was
chromatographed on silica gel (2 kg, 10.0 × 80 cm) using petroleum ether (60–90 °C)–ethyl acetate
system to yield nine fractions. Fr. 3 (3.58 g) was subjected to an Amberchrom GC161M column
eluted with EtOH/H2O, (3:2 to 9:1, v/v) to afford two fractions A and B. Fraction A (2.12) was
chromatographed on ODS eluted with MeOH/H2O (4:6, v/v), followed by purification over
semipreparative HPLC (45% MeOH in H2O, flow rate 2.0 ml/min, wavelength 210nm) to yield
compounds 6 (8.0 mg, retention time 35 min) and 7 (7.6 mg, retention time 21 min). Fraction B (0.74 g)
was subjected to Sephadex LH-20 (eluted with MeOH) and ODS column chromatography (eluted with
80% MeOH in H2O), followed by purification over semipreparative HPLC (92% MeOH in H2O, flow
rate 2.0 ml/min, wavelength 210 nm) to yield 4 (15.0 mg, retention time 27 min) and 5 (12.0 mg,
retention time 32 min). Fraction 4 (3.37 g) was fractionated by Amberchrom GC161M column
(EtOH/H2O, 3:2 to 9:1, v/v) to afford Fractions C and D. Fraction C (1.76 g) was purified on a
Sephadex LH-20 (eluted with MeOH) and a ODS column (MeOH/H2O 5:5) to give 10 (4.5 mg).
Fraction D (0.87 g) was subjected into a silica gel column eluted with petroleum/EtOAc (5:1 to 1:2,
v/v) to afford six major fractions, D1−D6. Fraction D2 was subjected to Sephadex LH-20 column
chromatography (eluted with MeOH) to obtain the major portion, which was purified by a
semipreparative HPLC (92% MeOH in H2O, flow rate 2.0 mL/min, wavelength 210 nm) to yield
compounds 2 (15.0 mg, retention time 31 min) and 3 (9.8 mg, retention time 35 min). Fraction D3 was
treated similarly to afford 1 (4.5 mg, retention time 33 min). Fr. 5 (12.37 g) was chromatographed over
Amberchrom GC161M column (EtOH/H2O, 3:2 to 9:1, v/v) to afford two fractions E and F. Fraction E
(7.56 g) was chromatographed over a silica gel column, eluted with petroleum ether (60–90°C)–ethyl
acetate (4:1 to 1:1), to afford four major fractions, E1–E4. Fraction E2 (0.78 g) was purified by
semipreparative HPLC (55% MeOH in H2O, flow rate 2.0 ml/min, wavelength 210 nm) to afford

Molecules 2012, 17
6431
compound 9 (10.3 mg, retention time 23 min). Using the same procedure, Fraction E3 gave 8 (8.5 mg,
retention time 27 min).
Wikstroelide Q (1): white amorphous powder; []2D0.0 +20.00 (c 0.22, MeOH). UV (MeOH) λmax (log ε)
275 (4.15) nm; IR (KBr) νmax 3441, 2930, 1713, 1637, 1604, 1453, 1388, 1281, 1172, 1114, 1073,
1
1034,and 921 cm−1; H-NMR (CDCl3, 400 MHz) and 13C NMR (CDCl3, 100 MHz) see Table 1;
HRESIMS m/z 687.3486 [M+Na]+ (calcd for C39H52O9Na, 687.3504).
Prostratin Q (5): colorless gum; []D20.0 +16.36 (c 0.03, MeOH). UV (MeOH) λmax (log ε) 263 (3.84)
nm; IR (KBr) νmax 3420,2927, 1714, 1641, 1460, 1377, 1328, 1262, 1132, 1078, and 999 cm−1;
1H-NMR (CDCl3, 400 MHz) and C-NMR (CDCl3, 100 MHz) see Table 1; HRESIMS m/z 579.2937
13
[M + Na]+ (calcd for C32H44O8Na, 579.2928).
3.4. Cytotoxicity Assays
Five human cancer cell lines, human myeloid leukemia HL-60, hepatocellular carcinoma SMMC-
7721, lung cancer A549, breast cancer MCF-7, and colon cancer SW480 cells, together with one
human normal cell line BEAS-2B (human bronchial epithelial), were assayed. Cells were cultured in
RPMI-1640 or in DMEM medium (Hyclone, USA), supplemented with 10% fetal bovine serum
(Hyclone, USA) in 5% CO2 at 37 °C. The antiproliferative assay was performed according to the MTT
(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method in 96-well microplates, as
reported previously, with slight modification. [14] Briefly, 100 μL of adherent cells was seeded into
each well of 96-well cell culture plates and allowed to adhere for 12 h before addition of test
compounds, while suspended cells were seeded just before the addition of the drug with initial density
of 1 × 105 cells/mL. Each cancer cell line was exposed to the tested compound at concentrations of
0.0625, 0.32, 1.6, 8, and 40 μM in triplicates for 48 h. Wells with DMSO were used as negative
controls, and DDP (cis-platin, Sigma, USA) and taxol were used as a positive control. After compound
treatment, cell viability was detected by a Bio-Rad 680 at λ = 595 nm and a cell growth curve was
graphed. IC50 values were calculated by Reed and Muench’s method.
4. Conclusions
In conclusion, two new diterpenoids, wikstroelide Q (1) and prostratin Q (5), together with three
known diterpenoids, pimelea factors P2 (2), P3 (3), and prostratin (4), and five known lignans,
(+)–epipioresinol (6), (+)–isolariciresinol (7), (–)–lariciresinol (8), (+)–episesaminone (9), and prestegane
B (10), were isolated from the buds of Wikstroemia chamaedaphne Meissn. Their structures were
elucidated by a combination of spectroscopic analyses. Compound 1 exhibited weak cytotoxic activity
against HL-60 cell lines with an IC50 value of 26.43 μM, but showed no active against SMMC-7721,
A549, MCF-7, SW480 and BEAS-2B cell lines in vitro (IC50 > 40 μM). Compounds 2–4 showed
moderate cytotoxic activities against HL-60, SMMC-7721, A549, MCF-7, SW480 and BEAS-2B cell
lines within the IC50 value range of 13–18 μM. While compounds 5–10 were inactive (IC50 > 40 μM).

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Acknowledgments
This work was financially supported by the National Natural Science Foundation of China (No.
31070311, to Y. Zhang), Key Program of the National Natural Science Foundation of Hubei Province
(No. 2010CD104, to Y. Zhang), Program for New Century Excellent Talents in University, State
Education Ministry of China (No. NCET-2008-0224, to Y. Zhang), Scientific Research Foundation for
the Returned Oversea Chinese Scholars, State Education Ministry of China (to G. Yao), Medical
Research Foundation of Huazhong University of Science and Technology (to G. Yao), and Program of
Recruited Top Talent of Sciences and Technology of Yunnan province (No. 2009c1120, to Y. Li).
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Sample Availability: Samples of the compounds 1–10 are available from the authors.
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