Intramolecular electrochemical dehydrogenative N-N bond formation for the synthesis of 1,2,4-triazolo[1,5-a] pyridines

Article abstract of DOI:10.1039/c9gc01895f

A metal- and oxidant-free intramolecular dehydrogenative N-N bond formation has been developed under mild and scalable electrolytic conditions. Various valuable 1,2,4-triazolo[1,5-a]pyridines were synthesized efficiently from the readily available N-(2-pyridyl)amidines. The reactions were conducted in a simple undivided cell under constant current conditions with ⁿBu₄NBr as both the redox mediator and the electrolyte. This protocol was applied to the efficient synthesis of key intermediates for anti-diabetic compounds.

Full text of DOI:10.1039/c9gc01895f

View Article Online
View Journal
Green
Chemistry
Cutting-edge research for a greener sustainable future
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: Y. Li, Z. Ye, N.
Chen, Z. Chen and F. Zhang, Green Chem., 2019, DOI: 10.1039/C9GC01895F.
Volume 20
This is an Accepted Manuscript, which has been through the
Number
May 2018
Pages 1919-2160
9
7
Royal Society of Chemistry peer review process and has been
accepted for publication.
Green
Chemistry
Cutting-edge research for a greener sustainable future
rsc.li/greenchem
Accepted Manuscripts are published online shortly after acceptance,
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
shall the Royal Society of Chemistry be held responsible for any errors
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
ISSN 1463-9262
PAPER
Paul T. Anastas et al.
The Green ChemisTREE: 20 years after taking root with the 12
principles
rsc.li/greenchem

Page 1 of 4
Green Chemistry
View Article Online
DOI: 10.1039/C9GC01895F
COMMUNICATION
a) Xu's electrochemical synthesis of triazolopyridines
Intramolecular Electrochemical
Dehydrogenative N–N Bond
Formation for the Synthesis of
1,2,4-Triazolo[1,5‑a]pyridines
R2
R2
NH2
R1
N
N
H2
+
+
R1
N
N
N-N bond formation
N
Received 00th January 20xx,
Accepted 00th January 20xx
b) Our previous electrochemical synthesis of triazolopyridines
H
N
H
DOI: 10.1039/x0xx00000x
N
R2
Yong Li,a, † Zenghui Ye,b, † Na Chen,a Zhenkun
R1
N
N
N
R1
H2
N
C-N bond formation
N-N bond formation
N
Chena and Fengzhi Zhang*a,b
R2
c) This work
H
A metal and oxidant-free intramolecular dehydrogenative N–N and
bond formation has been developed under mild and scalable sustainable
electrolytic conditions. Various valuable 1,2,4-Triazolo[1,5- synthetic
N
N
N
R1
R1
R2
H2
+
R2
N
N
H
a]pyridines were synthesized efficiently from the readily available approaches for the access of this heterocyclic scaffold are still
N-(2-pyridyl)amidines. The reactions were conducted in a simple required.
undivided cell under constant current condition with nBu4NBr as
both the redox mediator and electrolyte. This protocol was
Scheme 1 Electrochemical synthesis of triazolopyridines
applied to the efficient synthesis of key intermediate for anti-
diabetic compounds.
Electrochemical anodic oxidation, which uses electron to drive
the reaction and avoids the use of chemical oxidants, is recognized
as an environmentally friendly synthetic methodology.15 Despite
Introduction
the fact that electrochemical methods have made great progress in
16
the construction of C–C or C–heteroatom bonds,
the
Due to the special biological activities and electrical properties,
nitrogen-containing heterocycles constitute one of the largest and
most important groups of organic compounds.1 Among these, the
1,2,4-triazolo[1,5-a]pyridine nucleus is a privileged structural motif
widely found in biologically active natural products,
pharmaceuticals, agrochemicals and organic materials (Figure 1).2-8
The importance of this heterocyclic moiety has promoted the
development of many practical synthetic routes for the
preparation,
transformation and finding of specific properties of 1,2,4-
triazolo[1,5-a]pyridine derivatives. In 2009, Ueda and Nagasawa
reported a copper-catalyzed intermoleular synthetic approach to
triazolo[1,5-a]pyridine by using 2-aminopyridines and nitriles as
starting substrates,9a and the majority of synthetic routes rely on
the intramolecular oxidative cyclization of aminopyridine
derivatives (such as N‑Aryl amidines, guanidines) at high
temperature in the presence of either transition metal catalysts 9 or
stoichiometric amounts of external oxidants (such as NaClO,10
Pb(OAc)4,11 MnO2,12 PIFA13 and I214). Consequently, more efficient
electrochemical construction of N–N bonds is still very rare. In
2014, Baran and co-workers developed an unique method of
electrochemical dimerization of carbazoles and carbolines, which
was applied as the pivotal step for the first total synthesis of a rare
N–N linked dimeric natural product dixiamycin B.17 Later, Waldvogel
group achieved the novel access to pyrazolidin-3,5-diones and
phthalazin-1,4-diones through intramolecular elecrochemical N–N
bond formation of dianilides.18-19 Recently, Xu and co-workers
reported an electrochemical intramolecular N–N bond formation
for the synthesis of [1,2,3]triazolo[1,5-a]pyridines from 2-
acylpyridine hydrazines (Scheme 1a).20 And our group developed an
electrochemical synthesis of 1,2,4-triazolo[4,3-a]pyridines via a
metal- and oxidant-free intramolecular dehydrogenative C–N bond
formation (Scheme 1b).21 With our continued interest in developing
novel and efficient methodologies for the synthesis of privileged
heterocycles,21-22 herein we reported an electrochemical
intramolecular dehydrogenative N–N bond formation for the
synthesis of 1,2,4-triazolo[1,5-a]pyridines under metal- and oxidant-
free conditions (Scheme 1c).
Results and discussion
a. College of Pharmaceutical Science, Zhejiang University of Technology, 310014,
Hangzhou, P. R. China.
b. Collaborative Innovation Center of Yangtze River Delta Region Green
Pharmaceuticals, Zhejiang University of Technology, 310014, Hangzhou, P. R.
China
†These authors contribute equally.
*Corresponding author，E-mail: zhangfengzhi@zjut.edu.cn
Electronic Supplementary Information (ESI) available: [details of any
CO H
Figure 1. Representative 1,2,4-triazolo[21,5‑a]pyridines molecules
N
N
NH2
N
Me
Me
N
N
N
O
N
SO2NHtBu
anti-inflammatory
anti-diabetic
N
N
NH
N
EtO S

Green Chemistry
Page 2 of 4
COMMUNICATION
Journal Name
N-(2-pyridyl) amide 1a was used as the model substrate to test products in good to excellent yields (2b-2l). Both electron-
View Article Online
DOI: 10.1039/C9GC01895F
the oxidative cyclization conditions. The electrochemical reaction donating and withdrawing groups were tolerated. Also, the
was conducted in MeCN at room temperature under constant halogen such as F and Cl were compatible with the reaction
current electrolysis conditions using a three-necked round bottom conditions which allows for further transformations. Naphthyl (2i),
flask as an undivided cell, which equipped with a reticulated pyridine (2k) and thiophene (2l) carbonitriles were effective as
vitreous carbon (RVC) anode and a platinum plate cathode. Initially, well. It is worth mentioning that the methods are not only
different electrolytes were screened. There is no desired product compatible with aromatic nitriles, but alkyl nitriles are also well
n
n
formed with either NH4Br, Bu4NOAc or Bu4NBF4 as the electrolyte tolerated (2m-2q). The nitriles with either linear or cyclic alkyl
(Table 1, entries 1-3). It was found the product 2a was isolated in
35% yield when nBu4NCl (2.0 equiv) was used as the electrolyte,
which indicate that the halide ion might act as the redox mediator
C
Pt
I = 7 mA
H
N
N
N
N
N
and promote the N–N bond formation (Table 1, entry 4).23
Encouraged by this result, nBu4NI and nBu4NBr were then tested and
2a was obtained in fair yields (Table 1, entries 5-6). Increasing the
electrolyte’s loading to 3.0 equiv., the yield could be improved to
73% yield (Table 1, entries 7-8). Increasing the current from 6 mA to
7 mA the yield was further improved to 86% yield (Table 1, entry 9).
However, the yield was decreased slightly when the current was
further increased to 8 mA (Table 1, entry 10). Gratifyingly, using
graphite rod to replace RVC as anode led to 2a in 92% yield (Table 1,
entry 11), which tallies with Waldvogel’s observation for the
performance of reaction set-up during their electrochemical
synthesis of pyrazolidin-3,5-diones.18 Switching to the other
electrodes resulted in much lower yields (Table 1, entries 12-13).
R1
nBu4NBr, CH3CN
RT
N
H
R1
2
1
Cl
N
N
N
N
N
N
N
N
R
N
Cl
, 60%
N
2b
2c
2d
2e
, R = Me, 74%
2h
2i
, 76%
a
, R = OMe, 66%
N
N
a
N
, R = F, 65%
N
O
, R = Cl, 72%
, R = Br, 70%
N
N
2f
2g
O
2j, 60%a
, 62%
, R = CF3, 93%
2k
N
N
N
S
N
N
N
N
N
tBu
nBu
N
N
a
2l
, 70%
2m
2n
, 77%
, 62%
N
N
N
N
N
Table 1 Optimization of electrochemical conditionsa
N
N
Bn
N
H
N
N
N
N
2o
2p
, 81%
, 89%
2q
, 85%
N
H
N
a nBu4NI was used.
1a
2a
substituents can afford the desired products with good yields.
Entry Anode/cathode Electrolyte (equiv)
Current
6 mA
6 mA
6 mA
6 mA
6 mA
6 mA
6 mA
6 mA
7 mA
8 mA
7 mA
7 mA
7 mA
Yieldb (%)
n.d.
n.d.
n.d.
35
Scheme 2 Scope of nitrile derived substrates
1
2
RVC/Pt
RVC/Pt
RVC/Pt
RVC/Pt
RVC/Pt
RVC/Pt
RVC/Pt
RVC/Pt
RVC/Pt
RVC/Pt
C/Pt
NH4Br (2.0)
nBu4NOAc (2.0)
nBu4NBF4 (2.0)
nBu4NCl (2.0)
nBu4NI (2.0)
The scope of the aminopyridines was then studied (Scheme 3).
The substrates with simple methyl or ethyl substituents gave the
corresponding products in good to excellent yields (4a, 4b, 4f, 4g
and 4h). Again, both fluorine (4c) and chlorine (4d) were tolerated
under the reaction conditions although two chlorines in the
aminopyridine moiety decreased the reaction efficiency for N–N
bond formation (4i). A moderate yield could be achieved by
changing the aminopyridine to aminoquinoline (4j). In addition, the
substrates bearing tolyl (4k) or thienyl (4l) substitutents were also
effective by employing nBu4NI as the electrolyte in a mixture of
solvent.
3
4
5
54
6
nBu4NBr (2.0)
nBu4NI (3.0)
55
7
65
8
nBu4NBr (3.0)
nBu4NBr (3.0)
nBu4NBr (3.0)
nBu4NBr (3.0)
nBu4NBr (3.0)
nBu4NBr (3.0)
73
9
86
10
11
12
13
78
92
Pt/Pt
66
C/C
71
a
Reaction conditions: Two-electrode undivided cell: RVC anode
(100 PPI, 1 cm × 1 cm × 1 cm), Pt cathode (1 cm × 1 cm), 1a (0.3
mmol), MeCN (7 mL), 2.6 F/mol. b Isolated yields. graphite rod (ϕ
6 mm, about 10 mm immersion depth in solution). n.d. = not
detected
With the optimized conditions in hand, firstly we prepared the
N-(2-pyridyl)benzamidine 1 by condensation of 2-aminopyridine
with different nitriles and probed the effect of the substitutes on
nitrile side (Scheme 2). Initially, the nitriles with aromatic
substituent were tested which all gave the corresponding
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx

Page 3 of 4
Green Chemistry
Journal Name
COMMUNICATION
AgCl) at 0.83 V and 1.26 V (curve c). The oxidation potential of
N-(2-pyridyl)benzamide 1a was higher than that of bromide
View Article Online
DOI: 10.1039/C9GC01895F
C
Pt
I = 7 mA
H
N
N
N
N
N
R1
R1
Ph
ions (1.36 V vs. 1.26 V and 0.83 V). Compared to pure nBu4NBr,
the CV of nBu4NBr with N-(2-pyridyl)benzamide 1a exhibited an
obvious catalytic current, and the reduction peak disappeared
(curve d). This is the typical behaviour of mediator-assisted
oxidation and indicates that the oxidized form of nBu4NBr
reacts with the N-(2-pyridyl)benzamide 1a and therefore
cannot be reduced in the second part of the cycle. And these
results indicate that the reaction involves indirect
electrolysis.24
nBu4NBr, CH3CN
RT
N
H
Ph
4
3
Me
Et
N
F
N
N
N
N
N
N
N
Ph
Ph
Ph
Ph
Ph
N
4a
4b
4c
, 92%
, 90%
, 83%
Cl
N
N
N
N
N
N
Ph
Ph
N
N
N
MeO
Me
4d
4e
4f
, 73%
, 51%
, 66%
Me
Cl
N
N
N
N
Ph
Ph
N
N
N
N
Ph
N
Me
4g
Me
Cl
4i
a
a
, 68%
4h
, 66%
N
, 22%
Me
N
N
N
N
S
N
N
Ph
Ph
N
N
a,b,
a,b
4j
, 50%
4k
4l
, 80%
, 65%
a nBu4NI was used. b MeCN (5 mL) and THF (2 mL) were used as co-solvent.
Scheme 3 Scope of aminopyridine derived substrates
The scalability of this electrochemical dehydrogenative N–N bond
formation was then evaluated by performing an 8 mmol scale
reaction (Scheme 4). With almost the same ratio of 3 F/mol of
electricity, the cyclization of 1a smoothly furnished the desired
product 2a in 82% yield. This result demonstrates the potential
industrial applications of this electrochemical dehydrogenative
reaction. Furthermore, we demonstrated that our newly developed
electrochemical synthesis can be applied as the key step for the
synthesis of a series of compounds having anti-diabetic activity.
With pyridinamine 5 and phenylnitrile 6 as the starting materials,
the compound could be prepared efficiently through nucleophilic
substitution promoted by tin tetrachloride, electrochemical
dehydrogenative N–N bond formation, and demethylation with
aluminum trichloride, which could be further transformed into
various bioactive molecules.6b
Figure 1 Cyclic voltammograms. a: background; b: 1a (5 mM); c:
nBu4NBr (5 mM); d: 1a + nBu4NBr (5 mM).
According to the cyclic voltammograms results and literature
20
reports,13, a possible mechanism for this dehydrogenative N–N
bond formation was proposed as shown in Scheme 5. With nBu4NBr
as both the redox mediator and electrolyte, there are two possible
pathways leading to the product 2a. The first reaction pathway
(path a) could begin with the anodic oxidation of bromide ion to
form molecular bromine, which reacts with substrate 1a to afford
the intermediate A. A homolytic cleavage might lead to the
intermediate B which has a resonance structure C. Subsequent
oxidative cyclization and deprotonation would afford 2a. The other
pathway (path b) 1a might begin with the bromination of the imine
to give the intermediate D. A direct intramolecular cyclization might
Gram scale
generate the intermediate
deprotonation.
E
which would give 2a after
H
C
Pt
I = 42 mA
N
N
N
N
N
N
H
nBu4NBr, CH3CN
RT
1a
e-
2aa,
1.28g (82%)
e-
H
N
e-
H
Br
Further application
Br2
N
HBr
N
N
Me
NC
N
path b
Ph
Me
N
Ph
N
N
Br
N
H
SnCl4
N
N
D
+
OMe
OR2
-Br
H
1a
1/2 H2
Br-
NH2
OMe
path a
72%, 2 steps
7
e-
6
5
N
N
NH
Ph
N
Br2
Ph
N
N
R1O
Me
N
AlCl3
83%
N
-H+
N
N
OH
E
Br
ref. 6b
A
N
-e-
-H+
anti-diabetic
8
N
N
N
NH
N
NH
Ph
N
Br
Scheme 4 Gram scale reaction and further application
Ph
N
Ph
N
2a
B
C
To clarify the role of nBu4NBr, cyclic voltammetry (CV)
experiments were performed. As shown in Figure 1, N-(2-
pyridyl)benzamide 1a was oxidized to 1.36 V (vs. Ag / AgCl)
(curve b). Meanwhile, Bu4NBr showed two distinct oxidation
peaks (vs Ag / AgCl) and one reduction peak at 1.08 V (vs. Ag /
Scheme 5 Proposed mechanism
n
Conclusions
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3

Green Chemistry
Page 4 of 4
COMMUNICATION
Journal Name
Patel, S. B. Patel, A. Petrov, G. Scapin, J. Shang, R. S. Roy, A. Smith, J. K.
In conclusion, we have present an environmentally friendly
method to prepare valuable 1,2,4-triazolo[1,5 ‑a]pyridines via
dehydrogenative N–N bond formation. The key is the
employment of Bu4NBr or Bu4NI as both the redox mediator
and electrolyte in an undivided cell. Neither transition metals
nor additional oxidants are required for this simple and
scalable protocol.
Wu, S. Xu, B. Zhu, N. A. Thornberry, A. E. Weber, J. MeVdi.ewChAertmicl.e, O20nl0in6e,
DOI: 10.1039/C9GC01895F
49, 3614; (b) C. Hamdouchi, P. Maiti, A. M. Warshawsky, A. C. DeBaillie,
K. A. Otto, K. L. Wilbur, S. D. Kahl, A. P. Lewis, G. R. Cardona, R. W. Zink,
K. Chen, S. CR, J. P. Lineswala, G. L. Neathery, C. Bouaichi, B. A. Diseroad,
A. N. Campbell, S. A. Sweetana, L. A. Adams, O. Cabrera, X. Ma, N. P.
Yumibe, C. Montrose-Rafizadeh, Y. Chen, A. R. Mille, J. Med. Chem.,
2018, 61, 934.
For agrochemicals, see: K. Takao, M. Yukihiro, N. Kenkichi, M. Hiroto, K.
Masaki, I. Hodaka, JP2018024657, 2018.
For organic materials, see: W. Song, Y. Chen, Q. Xu, H. Mu, J. Cao,J.
Huang, J. Su, ACS Appl. Mater. Interfaces. 2018, 10, 24689.
n
n
7
8
9
Acknowledgements
(a) S. Ueda, H. Nagasawa, J. Am. Chem. Soc., 2009, 131, 15080. (b) X.
Meng, C. Yu, P. Zhao, RSC Adv., 2014, 4, 8612. (c) B. Bartels, C. G. Bolas,
P. Cueni, S. Fantasia, N. Gaeng, A. S. Trita, J. Org. Chem., 2015, 80, 1249;
This research was supported by the Natural Science Foundation of
China grant No. 21871234, Zhejiang Provincial Natural Science
Foundation of China for Distinguished Young Scholars under grant
No. LR15H300001. We also thank the Zhejiang Provincial Thousand-
Talent Program and Zhejiang University of Technology for financial
support.
10 V. J. Grenda, R. E. Jones, G. Gal, M. Sletzinger, J. Org. Chem., 1965, 30,
259.
11 K. T. Potts, H. R. Burton, J. Bhattacharyya, J. Org. Chem., 1966, 31, 260.
12 J. P. Raval, K. R. Desai, Arkivoc 2005, xiii, 21.
13 Z. Zheng, S. Ma, L. Tang, D. Zhang-Negrerie, Y. Du, K. Zhao, J. Org. Chem.,
2014, 79, 4687.
14 L. Song, X. Tian, Z. Lv, E. Li, J. Wu, Y. Liu, W. Yu, J. J. Chang, J. Org. Chem.,
2015, 80, 7219.
Conflicts of interest
There are no conflicts to declare.
15 For selected reviews, see: see: (a) M. Yan, Y. Kawamata, P. S. Baran,
Chem. Rev., 2017, 117, 13230; (b) J.-I. Yoshida, A. Shimizu, R. Hayashi,
Chem. Rev., 2018, 118, 4702; (c) K. D. Moeller, Chem. Rev., 2018, 118,
4817; (d) J. E. Nutting, M. Rafiee, S. S. Stahl, Chem. Rev., 2018, 118,
4834; (e) J.-I. Yoshida, K. Kataoka, R. Horcajada, A. Nagaki, Chem. Rev.,
2008, 108, 2265; (f) K. D. Moeller, Tetrahedron, 2000, 56, 9527; (g) J. B.
Sperry, D. L. Wright, Chem. Soc. Rev. 2006, 35, 605; (h) S. Tang, Y. Liu, A.
Lei, Chem. 2018, 4, 27; (i) N. Sauermann, T. H. Meyer, Y. Qiu, L.
Ackermann, ACS Catal., 2018, 8, 7086; (j) Q.-L. Yang, P. Fang, T.-S. Mei,
Chin. J. Chem., 2018, 36, 338; (k) A. Wiebe, T. Gieshoff, S. Möhle, E.
Rodrigo, M. Zirbes, S. R. Waldvogel, Angew. Chem. Int. Ed. 2018, 57,
5594; (l) Z. Ye, F. Zhang, Chin. J. Chem., 2019, 37, 513.
16 (a) H. Lund, O. Hammerich, Eds. Organic Electrochemistry, 4th ed.;
Marcel Dekker, Inc., 2001. (b) C. Moinet, In Encyclopedia of
Electrochemistry; A. J. Bard, M. Stratmann, Eds.; Vol. 8, Wiley-VCH:
Weinheim, 2004, pp. 341; (c) R. Francke, Beilstein J. Org. Chem., 2014,
10, 2858; (d) P. Wang, S. Tang, A. Lei, Green Chem., 2017, 19, 2092; (e) Y.
Jiang, K. Xu, C. Zeng, Chem. Rev., 2018, 118, 4485 and references
therein; (f) S.-K. Mo, Q.-H. Teng, Y.-M. Pan, H.-T. Tang, Adv. Synth. Catal.
2019, 361, 1756 – 1760.
17 B. R. Rosen, E. W. Werner, A. C. O’Brien, P. S. Baran, J. Am. Chem. Soc.,
2014, 136, 5571.
18 (a) T. Gieshoff, D. Schollmeyer, S. R. Waldvogel, Angew. Chem. Int. Ed.,
2016, 55, 9437; (b) T. Gieshoff, A. Kehl, D. Schollmeyer, K. D. Moller, S. R.
Waldvogel, J. Am. Chem. Soc., 2017, 139, 12317.
19 A. Kehl, T. Gieshoff, D. Schollmeyer, S. R. Waldvogel, Chem. Eur. J., 2018,
24, 590.
20 P. Xu, H.-C. Xu, ChemElectroChem, DOI:10.1002/celc.201900080.
21 Z. Ye, M. Ding, Y. Wu, Y. Li, W. Hua, F. Zhang, Green Chem., 2018, 20,
1732.
22 (a) Z. Ye, F. Wang, Y. Li, F. Zhang, Green Chem., 2018, 20, 5271; (b) M.
Liu, C. Zhang, M. Ding, B. Tang, F. Zhang, Green Chem., 2017, 19, 4509;
(c) C. Zhang, M. Liu, M. Ding, H. Xie, F. Zhang, Org. Lett., 2017, 19, 3418;
(d) H. Xie, M. Ding, M. Liu, T. Hu, F. Zhang, Org. Lett., 2017, 19, 2600; (e)
J. Guo, H. He, Z. Ye, K. Zhu, Y. Wu, F. Zhang, Org. Lett., 2018, 20, 5692; (f)
S. Yang; F. Wang; Y. Wu; T. Hu; Chem. Commun., 2018, 54, 3239-3242.
23 R. Francke, R. D. Little, Chem. Soc. Rev., 2014, 43, 2492.
24 For selected samples of indirect electrochemical heterocyclic
construction methods (a) Y. Wu, H. Yi, A. Lei, ACS Catal., 2018, 8, 1192;
(b) L. Zhu, P. Xiong, Z.-Y. Mao, Y.-H. Wang, X. Yan, X. Lu, H.-C. Xu, Angew.
Chem. Int. Ed., 2016, 55, 2226; (c) Y.-Y. Jiang, S. Liang, C.-C. Zeng, L.-M.
Hua, B.-G. Sun, Green Chem., 2016, 18, 6311. （d） Z.-W. Hou, H. Yan, J.-
S. Song, H.-C. Xu, Chin. J. Chem. 2018, 36, 909. (e) Z.-W. Hou, Z.-Y. Mao,
Y. Y. Melcamu, X. Lu, H.-C. Xu, Angew. Chem. Int. Ed. 2018, 57, 1636.
Notes and references
1
2
E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem., 2014, 57, 10257.
(a) M. Nettekoven, B. Püllmann, S. Schmitt, Synthesis, 2003, 11, 1649; (b)
G. Bergamini, K. Bell, S.Shimamura, T. Werner, A. Cansfield, K. Müller, J.
Perrin, C. Rau, K. Ellard, C. Hopf, C. Doce, D. Leggate, R. Mangano, T.
Mathieson, A. O’Mahony, I. Plavec, F. Rharbaoui, F. Reinhard, M. M.
Savitski, N. Ramsden, E. Hirsch, G. Drewes, O. Rausch, M. Bantscheff, G.
Neubauer, Nat. Chem. Biol. 2012, 8, 576; (c) K. Bell, M.Sunose, K.Ellard,
A. Cansfield, J. Taylor, W. Miller, N. Ramsden, G. Bergamini, G.
Neubauer, Bioorg. Med. Chem. Lett., 2012, 22, 5257; (d) M. Siu, R.
Pastor, W. Liu, K. Barrett, M. Berry, W. S. Blair, C. Chang, J. Z. Chen, C.
Eigenbrot, N. Ghilardi, P. Gibbons, H. He, C. A. Hurley, J. R. Kenny, S. C.
Khojasteh, H. Le, L. Lee, J. P. Lyssikatos, S. Magnuson, R. Pulk, V. Tsui, M.
Ultsch, Y. Xiao, B.-Y. Zhu, D. Sampath, Bioorg. Med. Chem. Lett., 2013,
23, 5014; (e) Y. Oguro, D. R. Cary, N. Miyamoto, M. Tawada, H. Iwata, H.
Miki, A. Hori, S. Imamura, Bioorg. Med. Chem. Lett., 2013, 23, 4714; (f) S.
Ahmed, A. Ayscough, G. R. Barker, H. E. Canning, R. Davenport, R.
Downham, D. Harrison, K. Jenkins, N. Kinsella, D. G. Livermore, S. Wright,
A. D. Ivetac, R. Skene, S. J. Wilkens, N. A. Webster, A. G. Hendrick, J.
Med. Chem. 2017, 60, 5663.
3
4
5
For anti-cancer activity, see: (a) B. J. Dugan, D. E. Gingrich, E. F. Mesaros,
K. L. Milkiewicz, M. A. Curry, A. L. Zulli, P. Dobrzanski, C. Serdikoff, M.
Jan, T. S. Angeles, M. S. Albom, J. L. Mason, L. D. Aimone, S. L. Meyer, Z.
Huang, K. L. Wells-Knecht, M. A. Ator, B. A. Ruggeri, B. D. Dorsey, J. Med.
Chem., 2012, 55, 5243; (b) X.-M. Wang, J. Xu, Y.-P. Li, H. Li, C.-S. Jiang,
G.-D. Yang, S.-M. Lu, S.-Q. Zhang, Eur. J. Med. Chem., 2013, 67, 243.
For anti-bacterial activity, see: S. P. East, C. B. White, O. Barker, S.
Barker, J. Bennett, D. Brown, E. A. Boyd, C. Brennan, C. Chowdhury, I.
Collins, E. Convers-Reignier, B. W. Dymock, R. Fletcher, D. J. Haydon, M.
Gardiner, S. Hatcher, P. Ingram, P. Lancett, P. Mortenson, K.
Papadopoulos, C. Smee, H. B. Thomaides-Brears, H. Tye, J. Workman, L.
G. Czaplewski, Bioorg. Med. Chem. Lett., 2009, 19, 894.
For anti-inflammatory activity, see: (a) M. Sunose, K. Bell, K. Ellard, G.
Bergamini, G. Neubauer, T. Werner, N. Ramsden, Bioorg. Med. Chem.
Lett., 2012, 22, 4613; (b) C. J. Menet, S. R. Fletcher, G. V. Lommen, R.
Geney, J. Blanc, K. Smits, N. Jouannigot, P. Deprez, E. M. van der Aar, P.
Clement-Lacroix, L. Lepescheux, R. Galien, B. Vayssiere, L. Nelles, T.
Christophe, R. Brys, M. Uhring, F. Ciesielski, L. V. Rompaey, J. Med.
Chem., 2014, 57, 9323.
6
For anti-diabetic activity, see: (a) S. D. Edmondson, A. Mastracchio, R. J.
Mathvink, J. He, B. Harper, Y. J. Park, Y. M. Beconi, J. D. Salvo, G. J.
Eiermann, H. He, B. Leiting, J. F. Leone, D. A. Levorse, K. Lyons, R. A.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx