Design, synthesis of novel C-3′-N-sulfonyl modified taxane analogues from 1-deoxybaccatin VI and their impact on anti-HCC activity

Article abstract of DOI:10.1080/10286020.2019.1691999

A new series of C-3′-N-sulfonyl paclitaxel analogs were designed and synthesized from 1-deoxybaccatin VI and their structures were confirmed by ¹H NMR, ¹³C NMR and high resolution MS. The synthesized compounds were evaluated for their in vitro anti-Hepatocellular carcinoma (HCC) activity against human hepatoma (HepG2) cell line. Bioassay results showed that compounds 17c, 17d and 17f exhibited more potent inhibitory activity against HepG2 cell line in comparison with paclitaxel. It is suggested that paclitaxel analogs containing the C-3′-N-sulfonyl could be considered as a precursor structure for further synthesis of more potent analogues.

Full text of DOI:10.1080/10286020.2019.1691999

Journal of Asian Natural Products Research
ISSN: 1028-6020 (Print) 1477-2213 (Online) Journal homepage: https://www.tandfonline.com/loi/ganp20
Design, synthesis of novel C-3′-N-sulfonyl modified
taxane analogues from 1-deoxybaccatin VI and
their impact on anti-HCC activity
Yan-Ru Xiao, Yong-Mei Cui, Cheng-Hu Xie, Wei-Qing Qiu & Hai-Xia Lin
To cite this article: Yan-Ru Xiao, Yong-Mei Cui, Cheng-Hu Xie, Wei-Qing Qiu & Hai-Xia Lin
(2019): Design, synthesis of novel C-3′-N-sulfonyl modified taxane analogues from 1-deoxybaccatin
VI and their impact on anti-HCC activity, Journal of Asian Natural Products Research, DOI:
10.1080/10286020.2019.1691999
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JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
https://doi.org/10.1080/10286020.2019.1691999
Design, synthesis of novel C-30-N-sulfonyl modified
taxane analogues from 1-deoxybaccatin VI and their
impact on anti-HCC activity
Yan-Ru Xiao, Yong-Mei Cui, Cheng-Hu Xie, Wei-Qing Qiu and Hai-Xia Lin
Department of Chemistry, College of Sciences, Shanghai University, Shanghai 200444, China
ABSTRACT
ARTICLE HISTORY
A new series of C-30-N-sulfonyl paclitaxel analogs were designed
and synthesized from 1-deoxybaccatin VI and their structures
were confirmed by 1H NMR, 13C NMR and high resolution MS.
The synthesized compounds were evaluated for their in vitro anti-
Hepatocellular carcinoma (HCC) activity against human hepatoma
(HepG2) cell line. Bioassay results showed that compounds 17c,
17d and 17f exhibited more potent inhibitory activity against
HepG2 cell line in comparison with paclitaxel. It is suggested that
paclitaxel analogs containing the C-30-N-sulfonyl could be consid-
ered as a precursor structure for further synthesis of more
potent analogues.
Received 28 September 2019
Accepted 8 November 2019
KEYWORDS
Paclitaxel; 1-deoxybaccatin
VI; synthesis; anti-HCC
activity; 30-N-sulfonyl
1. Introduction
Hepatocellular carcinoma (HCC) is a rapidly fatal disease with a third highest mortal-
ity rate among all cancers [1]. Although several therapeutic approaches and systemic
drugs including gemcitabine and octreotide have been used for patients with
CONTACT Hai-Xia Lin
haixialin@staff.shu.edu.cn
Department of Chemistry, College of Sciences, Shanghai
University, Shanghai 200444, China
Supplemental data for this article is available online at https://doi.org/10.1080/10286020.2019.1691999.
ß 2019 Informa UK Limited, trading as Taylor & Francis Group

2
Y.-R. XIAO ET AL.
advanced HCC, the prognosis of these patients is not favorable yet [2]. Therefore, it
is necessary to develop new drugs for the treatment of advanced HCC.
Paclitaxel (1), a diterpenoid natural compound originally isolated from the bark of
Taxus brevifolia, is one of the most important antitumor agents, has been used for
therapy of different types of cancers, including breast, gastric, ovarian, and non-small
cell lung carcinomas (Figure 1) [3–6]. Mechanistically, paclitaxel blocks cell cycle and
induces cell death by stabilizing microtubules and disrupting microtubule disruption
in cell division [7]. There are some reports on the activity of paclitaxel against HCC
in vitro and in vivo. Iesalnieks reported that paclitaxel promoted liver graft survival
in rats and inhibited HCC growth in vitro and was a potentially useful drug for
transplant patients with liver cancer [8]. Okano indicated the growth inhibition of
liver cancer cells by paclitaxel and the involvement of extracellular signal-regulated
kinase and apoptosis [9]. Additionally, paclitaxel has also been reported to possess
significant growth inhibitory effects on HCC in nude mice [10]. These results sug-
gest that paclitaxel could be a promising candidate with excellent therapeutic effi-
cacy for HCC therapy. Thus, further exploration of the effects of paclitaxel
analogues in HCC could be fruitful for the discovery of new candidates for the
treatment of advanced HCC.
A large number of structure-activity relationship (SAR) studies of paclitaxel have
revealed that the C-1 hydroxy group is not necessary for the activity of paclitaxel [11].
Deoxygenation of the C-1-hydroxyl group of paclitaxel had been reported to be a dif-
ficult procedure [12,13]. Thus, development of a procedure for synthesis of 1-deoxy-
paclitaxel analogs will be very significant. 1-Deoxybaccatin VI 2 (Figure 1) that
possesses the typical tetracyclic taxoid core while lacking the C-1 hydroxy group is
readily available from Rehd. var. mairei in good yield [14]. Hence, the development
of a method using 1-deoxybaccatin VI as the starting material for preparation of new
active taxoids will be of value. Structure-activity studies also indicate that the C-13
side chain is essential for antitumor activity, and the stereochemistry of the side chain
at the C-20 and C-30 is crucial for biological activity [15]. It is reported that analogues
without 30-N-acyl groups are significantly less active than paclitaxel, and aliphatic
and heteroaromatic 30-N-acyl analogs are slightly more active than paclitaxel [16,17].
In our previous study, the novel C-30-N-acyl modified 1-deoxybaccatin VI taxane
analogues 3 and 4 (Figure 1) had been synthesized, and biologically tested results
showed these two compounds have good activities against HepG2 cell line [18].
The sulfonamides constitute an important class of drugs, with antibacterial, anti-
parasitic, anti-inflammatory, diuretic, hypoglycemic, anti-epileptic, antithyroid and
anticancer activities among others [19]. A large number of sulfonamide derivatives
have been reported to have remarkable antitumor activity in vitro and in vivo [20],
which provide guidance for designing paclitaxel analogs with sulfonamide groups.
Three new 30-N-tert-butylsulfonyl docetaxel analogues 5–7 (Figure 1) were synthe-
sized and shown to exhibit potent cytotoxicities against human tumor cell lines Eca-
109, SKOV3, SMMC-7721, HCT-8, PC3, MCF-7, HeLa and KB [17]. Thus, according
to the bioisosteric [21] nature of oxygen and sulfur atoms and the rapid metabolism
of sulfur atoms in the body (oxidation to sulfoxide or sulfone), the carbonyl group at
the C-30-N is replaced by a sulfone group. Sixteen novel C-30-N-sulfonyl modified 1-

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
3
Figure 1. Structures of compounds 1–7.
deoxybaccatin VI taxane analogues were designed, synthesized and evaluated for anti-
HCC activity.
2. Results and discussion
2.1. Chemistry
As previously reported, paclitaxel side chains were synthesized by different
methods [22–24]. Among them, it is preferred to synthesize an oxazolidine side
chain precursor by using commercially available material (2 R, 3S)-3-phenylisoserine 9
as starting material. As depicted in Scheme 1, compound 9 was transformed into sul-
fonamides 10a-h with sulfonyl chloride after formation of the methyl ester. Cyclic
protection using methoxypropene in the presence of a catalytic amount of pyridinium
para toluenesulfonate (PPTS) afforded the oxazolidine side chain precursors 11a–h in
80–90% yields.
The synthesis of compounds 13a-h is shown in Scheme 1. Treatment of 1-deoxy-
baccatin VI 2 with Red-Al at -20 ꢀC gave 13-deacetyl-1-deoxybaccatin VI 8 in 77%
yield, that was proved to be a very efficient way for the synthesis of analogues retain-
ing the C-7, C-9, and C-10 acetoxyl groups [21]. Then the side chain intermediates
11a-h were coupled with 8 after saponification in the presence of dicyclohexylcarbo-
diimide (DCC) and 4-dimethylaminopyridine (DMAP) at 50 ꢀC to provide the corre-
sponding cyclic ester intermediates 12a-h in 85%-95% yields. After hydrolysis of the
acetonide protecting groups of side chain, the final products 13a-h were afforded.

4
Y.-R. XIAO ET AL.
Scheme 1. The synthetic route of compounds 13a-h and 17a-h. Reagents and conditions: (a) Red-
Al, THF, -20ꢀC, 0.5 h; (b) NH2NH2ꢁH2O, EtOH, rt, 82%; (c) 2,2-dimethoxypropane, montmorillonite
K10, CH2Cl2, rt, 97%; (d) SOCl2, MeOH, 0 ꢀC to rt, overnight; (e) sulfonyl chloride, THF, sat.NaHCO3,
0 ꢀC to rt, 2 h, 80-90%; (f) 2-methoxypropene, PPTS, toluene, 2 h, 90 ꢀC, 80-90%;(g) KOH, MeOH, rt,
2 h; (h) 8 or 15, DCC, DMAP, toluene, 50 ꢀC, 2 h, 80- 90%; (i) formic acid, rt, 4 h, 25-35%.
To compare with these compounds 13a-h with three acetoxyl groups on the parent
skeleton, we also synthesized a series of 1-deoxypaclitaxel analogues bearing different
substituted groups at the C-30-N-sulfonyl position and three hydroxyls at the C-7, C-
9 and C-10 positions in similar method. The synthesis of the compounds 17a-h is
illustrated in Scheme 1. Starting from compound 8, which was transformed to
7,9,10,13-tetradeacetylbaccatin VI 14 upon treatment with hydrazine hydrate in etha-
nol. Subsequently, the C-9 and C-10 hydroxyl groups were selectively protected with
2,2-dimethoxypropane catalyzed by montmorillonite K10 to give compound 15 in
97% yield. Then the side chain intermediates 11a-h were coupled with 15 after
saponification in the presence of DCC and DMAP at 50 ꢀC to provide the corre-
sponding intermediates 16a-h in 85%-95% yields. After removing the acetonide pro-
tecting group of 16a-h with formic acid at room temperature for 4 h, the final
products 17a-h were afforded.
2.2. Cytotoxicity to HepG2 cell line
In our previous study, we had found that the C-30-N-acyl modified 1-deoxybaccatin
VI taxane analogues 3 and 4 mentioned in the introduction had good anti-HCC
activities, especially compound 3 which exhibited a 2.5-fold higher cytotoxicity than
paclitaxel to the HepG2 cell line [18]. Therefore, we explore whether C-30-N-sulfonyl
modified taxane analogs we synthesized also have good activities against that cell line.
The in vitro anti-HCC activities of paclitaxel and the newly synthesized compounds
13a-h and 17a-h were assayed for effect in HepG2 cell line by CCK-8 method in ser-
ies of bioassay. The inhibitory activities (IC50) are summarized in Table 1.

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
5
Table 1. Cytotoxicity (IC50a) values against HepG2 for paclitaxel and its analogues 13a-h and
17a-h.
IC50(nM)
HepG2b
IC50(nM)
HepG2b
Compounds
Compounds
13a
13b
13c
13d
13e
13f
13g
13h
72.72
>100
>100
>100
52.68
154.97
>100
64.34
17a
17b
17c
17d
17e
17f
95.31
33.03
3.82
5.04
40.71
13.01
>100
>100
17g
17h
paclitaxel
46.47
aCytotoxicity (IC50) was assayed by CCK-8 method under which growing human tumor cell lines were exposed
for 48 h.
bHepatoma cell line.
As reported in Table 1, anti-HCC activities of six derivates were found in the
range of 3.82–52.68 nM. Among them, three compounds 17c, 17d and 17f showed
potent cytotoxicity with IC50 values of 3.82 nM, 5.04 nM and 13.01 nM, respectively,
and they were 5–12 times more cytotoxic than paclitaxel against HepG2 cell line.
These three compounds also showed better anti-HCC activities than the novel C-30-
N-acyl modified 1-deoxybaccatin VI taxane analogs 3 and 4 [18]. The result indicated
that compounds 17c, 17d and 17f may be potential anti-HCC products and demon-
strated the rationality and correctness we originally design. Another three compounds
17 b, 17e, 13e exhibited an activity almost similar to standard reference paclitaxel
with IC50 value of 46.47nM. Whereas other compounds (13a-d, 13f-h, 17a and 17g-h)
showed low toxicity against the tested liver carcinoma cells. Moreover, compounds
17b-f have higher cytotoxicity than 13 b-f. In comparison with their structures, com-
pounds 17 b-f have the three hydroxyl groups at the C-7, C-9 and C-10 positions
instead of the acetoxyl group of compound 13b-f. As illustrated by the results above,
these 1-deoxypaclitaxel analogues with three hydroxyls at the C-7, C-9 and C-10 posi-
tions would be valuable for enhancing the anti-HCC activity.
Based on the above-mentioned anti-HCC study, we selected compounds 17 b-d,
17f to further investigate its in vitro cell growth inhibitory activity against human
lung cancer cell line A549 and its resistant cell line A549/T. The in vitro antitumor
activities were evaluated by MTT method. As shown in Table 2, compound 17d
showed comparable activity to paclitaxel against A549 and A549/T cell lines with
IC50 values of 0.093 lM and 1.454 lM respectively. However, compounds 17 b, 17c
and 17f exhibited weak activity compared to paclitaxel against A549 and A549/T cell
lines. The preliminary tests showed that C-30-N-sulfonyl-modified taxane analogue
17d also exhibited potent anti-lung cancer activity.
In conclusion, we synthesized some C-30-N-sulfonyl modified paclitaxel analogues
to investigate the effect of the C-30-N sulfonyl substituents for anti-HCC activity. The
compounds 17 b-f showed remarkable anti-HCC activity. Among them, compounds
17c and 17d are the most potent compounds presenting IC50 values on HepG2 cells
of 3.82 and 5.04 nM compared to 46.47 nM of paclitaxel. Our findings show that the
substituents of the sulfonyl group at the C-30-N position have a significant effect on
the anti-HCC activity. At the same time, compound 17d showed comparable activity

6
Y.-R. XIAO ET AL.
Table 2. Cytotoxicity (IC50a) values for paclitaxel and its analogues 17b–d, 17f.
Compounds
IC50(lM）
17b
17c
17d
17f
Paclitaxel
A549b
>10
>10
>10
>10
0.093 0.018
1.454 0.508
>10
>10
0.020 0.001
1.406 0.167
A549/Tc
aCytotoxicity (IC50) was assayed by MTT method under growing human tumor cell lines were exposed for 72 h.
bHuman lung cancer cell line.
cHuman lung cancer resistant cell line.
to paclitaxel against A549 and A549/T cell lines. The IC50 values of two series 17 b-f
and 13 b-f could lead to the conclusion that 1-dexoypaclitaxel analogues with three
hydroxyls at the C-7, C-9 and C-10 positions have a conspicuous enhancement in
anti-HCC activity. Therefore, this may be an important orientation in finding candi-
dates from C-30-N-sulfonyl modified paclitaxel analogues that can be used in liver
cancer treatment in the future.
3. Experimental
Experimental procedure, 1H NMR, 13C NMR data of compounds 8, 13a-h, 14, 15,
17a-h are available in Supplementary data.
3.1. General experimental procedures
All reported yields are obtained after column chromatography or thin-layer chroma-
tography (TLC). Column chromatography was performed with silica-gel H (Qingdao
Marine Chemical Inc., Qingdao, China). TLC was conducted on silica gel GF254
plates (Qingdao Marine Chemical Factory, Qingdao, China). The NMR spectra were
1
measured with a Bruker Avance/AV 500 MHz (13C: 125.7 MHz, H: 500 MHz) spec-
1
trometer (Bruker BioSpin AG, Fallanden, Switzerland). H and 13C NMR spectra
were recorded with tetramethylsilane as internal standard in CDCl3. Chemical shifts
(d) are given in ppm. MSs were recorded on a Thermo Finnigan LCQ Advantage
Mass spectrometer (Agilent Technologies Singapore(sale)pte, Singapore). All chemi-
cals were dried or purified according to standard procedures prior to use.
3.2. General procedure for the synthesis of compounds 17c and 17d
HCOOH (>98%, 5 ml) was added to compounds 16c-d, and the reaction mixture
was stirred at room temperature for 4 h. Then the resulting solution was neutralized
by addition of saturated NaHCO3. After extracted with EtOAc, the combined organic
phase was washed with brine, dried over anhydrous Na2SO4. The crude products was
purified by thin layer chromatography, yielding products 17c-d as white solid.
3.2.1. 30-N-Debenzoyl-N-(3-bromo)-phenylsulfonyl-9(R)-dihydro-10-deacetyl-9,10-
dihydroxy-1-deoxypaclitaxel (17c)
1
White solid. Yield 33%. H NMR (500 MHz, CDCl3) d (ppm): 8.12 (d, J ¼ 6.0, Hz,
2 H, Ph-H), 7.58-7.48 (m, 2 H, Ph-H), 7.47-7.35 (m, 4 H, m-Br-Ph-H), 7.14-6.95 (m,

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
7
6 H, Ph-H), 6.47 (t, J ¼ 8.42 Hz, 1 H, 13-H), 6.44 (dd, J ¼ 9.6, 3.2 Hz, 1 H, 2-H), 6.03-
5.90 (m, 1 H, 3’-H), 5.14 (d, J ¼ 6.9 Hz, 1 H, 2’-H), 5.01-4.94 (m, 2 H, 5-H and 10-H),
4.49-4.40 (m, 2 H, 20-H and 9-H), 4.29 (d, J ¼ 8.0 Hz, 1 H, 20-H), 4.19 (t, J ¼ 8.8 Hz,
1 H, 7-H), 4.06 (br, 1 H), 2.15 (s, 3 H, CH3CO), 2.10 (d, J ¼ 4.8 Hz, 1 H, 3-H), 2.08-
2.06 (m, 2 H, 14-H and 6-H), 1.89 (d, J ¼ 6.6 Hz, 1 H, 1-H), 1.86 (s, 3 H, CH3), 1.82
(s, 3 H, CH3), 1.74-1.68 (m, 2 H, 14-H and 6-H), 1.29 (s, 3 H, CH3), 1.27 (s, 3 H,
CH3); 13C NMR (125 MHz, CDCl3) d (ppm): 171.4, 165.7 142.2, 139.8, 135.2, 130.1,
130.0, 129.9, 128.5, 128.4, 127.1, 126.9, 125.2, 122.6, 99.6, 99.5, 78.9, 75.8, 71.3, 69.3,
65.3, 59.4, 53.5, 47.5, 45.2, 42.6, 42.0, 38.3, 37.7, 36.3, 29.7, 26.2, 25.6, 21.3, 20.3, 18.3,
17.6, 17.4, 16.1, 15.7, 14.2, 13.6. HR-ESI-MS: m/z 912.2220 [M þ H]þ (calcd for
C44H51BrNO13S, 912.2264).
3.2.2. 30-N-Debenzoyl-N-(2-bromo)-phenylsulfonyl-9(R)-dihydro-10-deacetyl-9,10-
dihydroxy-1-deoxypaclitaxel (17d)
1
White solid. Yield 28%. H NMR (500 MHz, CDCl3) d (ppm): 8.07-8.05 (m, 2 H, Ph-
H), 7.65(t, J ¼ 1.8 Hz, 1 H, Ph-H), 7.54-7.51 (m, 1 H, Ph-H), 7.45-7.37 (m, 4 H, Ph-H),
7.11 (d, J ¼ 7.0 Hz, 3 H, o-Br-Ph-H), 7.06-7.03 (m, 3 H, Ph-H), 6.06 (t, J ¼ 8.6 Hz, 1 H,
13-H), 5.76 (dd, J ¼ 8.4, 3.7 Hz, 1 H, 2-H), 5.66 (d, J ¼ 6.7 Hz, 1 H, 30-H), 5.32 (d,
J ¼ 6.0 Hz, 1 H, 2’-H), 5.07 (d, J ¼ 8.3 Hz, 1 H, 5-H), 4.83 (d, J ¼ 9.6 Hz, 1 H, 10-H),
4.52 (d, J ¼ 9.8 Hz, 1 H, 9-H), 4.23 (d, J ¼ 8.5 Hz, 1 H, 20-H), 4.17 (t, J ¼ 8.7 Hz, 1 H,
7-H), 4.03 (d, J ¼ 8.2 Hz, 1 H, 20-H), 3.65 (d, J ¼ 5.9 Hz, 1 H, 3-H), 2.12-2.07 (m, 2 H,
14-H and 6-H), 2.01 (s, 3 H, CH3CO), 1.92 (d, J ¼ 6.1 Hz, 1 H, 1-H), 1.82 (s, 3 H,
CH3), 1.79 (s, 3 H, CH3), 1.64-1.60 (m, 2 H, 14-H and 6-H), 1.26 (s, 3 H, CH3), 1.25
(s, 3 H, CH3); 13C NMR (125 MHz, CDCl3) d (ppm): 171.2, 165.5, 144.0, 142.0, 136.1,
135.2, 133.5, 130.1, 129.3, 128.5, 128.4, 128.2, 127.1, 125.3, 124.3, 122.6, 75.0, 74.2,
71.9, 71.9, 59.7, 67.1, 66.9, 55.9, 52.2, 51.0, 50.0, 48.2, 47.5, 45.3, 40.3, 31.9, 30.4, 29.8,
26.3, 22.7, 21.2, 18.4, 17.6, 17.1, 16.1, 15.7, 14.1, 13.6. HR-ESI-MS: m/z 912.2232
[M þ H]þ (calcd for C44H51BrNO13S, 912.2264).
Acknowledgements
The authors are grateful to Prof. Junjie Xiao, School of Life Sciences Shanghai University, for
their help in the activity assay. The authors also thank Dr. H. Deng, the Instrumental Analysis
& Research Center of Shanghai University, for structural analysis.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was financially supported by the the National Natural Science Foundation of China
[grant numbers 21272154 & 81202402].

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Y.-R. XIAO ET AL.
References
[1] J. Bruix, G.J. Gores, and V. Mazzaferro, Gut 63, 844 (2014).
[2] J. Balogh, D. Victor, E.H. Asham, S.G. Burroughs, M. Boktour, A. Saharia, X. Li, M.
Ghobrial, and H. Monsour, J. Hepatocell. Carcinoma 3, 41 (2016).
[3] I. Ojima, X. Wang, Y. Jing, and C. Wang, J. Nat. Prod. 81, 703 (2018).
[4] A. Farsi and P.M. Ellis, Front. Oncol. 4, 157 (2014).
[5] M. Lichtman, J. Geriatr. Oncol. 5, 223 (2014).
ꢀ
ꢀ
[6] M. Cusido, J. Palazon, and M. Bonfill, Biotechnol. Prog. 18, 418 (2002).
[7] D. Zhang, R. Yang, S. Wang, and Z. Dong, Drug. Des. Devel. Ther. 8, 279 (2014).
[8] I. Iesalnieks, S. Tange, M.N. Scherer, C. Graeb, E. Frank, K.W. Jauch, and E.K. Geissler,
Transplant. P. 34, 2316 (2002).
[9] J.-I. Okano, T. Nagahara, K. Matsumoto, and Y. Murawaki, Oncol. Rep. 17, 1195
(2007).
[10] Z.L. Zhang, Z.S. Liu, and Q. Sun, Chin. Med. J. 118, 1688 (2005).
[11] D.G. Kingston, M.D. Chordia, and P.G. Jagtap, J. Org. Chem. 64, 1475 (1994).
[12] S.-H. Chen, S. Huang, Q. Gao, J. Golik, and V. Farina, J. Org. Chem. 59, 1475 (1994).
[13] D.L. Yin, Y. Sekiguchi, and K. Kameo, Chinese Phys. Lett. 9, 373 (1998).
[14] H.X. Lin, M. Li, J.M. Chen, and M.Q. Chen, Chin. J. Chem. 22, 751 (2010).
ꢀ
ꢀ
[15] F. Gueritte-Voegelein, D. Guenard, and F. Lavelle, J. Med. Chem. 34, 992 (1991).
ꢀ
[16] Y.-T. Ma, Y. Yang, P. Cai, D.-Y. Sun, P.A. Sanchez-Murcia, X.-Y. Zhang, W.-Q. Jia, L.
Lei, M. Guo, F. Gago, H. Wang, and W.-S. Fang, J. Nat. Prod. 81, 524 (2018).
[17] B. Ke, Y. Qin, F. Zhao, and Y. Qu, Bioorg. Med. Chem. Lett. 18, 4783 (2008).
[18] Q.F. Li, H.X. Lin, Y.M. Cui, and P.P. Xu, Eur. J. Med. Chem. 104, 97 (2015).
[19] A. Scozzafava, T. Owa, A. Mastrolorenzo, and C. Supuran, Curr. Med. Chem. 10, 925
(2003).
[20] F. Carta, A. Scozzafava, and C.T. Supuran, Expert. Opin. Ther. Pat. 22, 747 (2012).
[21] S.R. Langdon, P. Ertl, and N. Brown, Mol. Inf. 29, 366 (2010).
[22] J. Chang, Y.-P. Hao, X.-D. Hao, H.-F. Lu, J.-M. Yu, and X. Sun, Molecules 18, 10189
(2013).
[23] D.G.I. Kingston, A.G. Chaudhary, A.A.L. Gunatilaka, and M.L. Middleton, Tetrahedron.
Lett. 35, 4483 (1994).
[24] H.F. Lu, X. Sun, L. Xu, L.G. Lou, and G.Q. Lin, Eur. J. Med. Chem. Chem. 44, 482
(2009).