Metal-free cyclization of unsaturated hydrazones for the divergent assembly of pyrazolones and pyrazolines

Article abstract of DOI:10.1039/c9cc04039k

An oxidative cyclization of β,γ-unsaturated hydrazones for the divergent assembly of pyrazolones and pyrazolines under metal-free conditions is presented. This divergent synthetic strategy was achieved by controlling the reaction atmosphere. A number of p

Full text of DOI:10.1039/c9cc04039k

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Metal-free Cyclization of Unsaturated Hydrazones for the
Divergent Assembly of Pyrazolones and Pyrazolines
Xiaobing Liu,a Zhou Yaoa and Qiuling Song*a,b
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
An oxidative cyclization of β,γ-unsaturated hydrazones for the metal-free cyclization of β,γ-unsaturated hydrazones is limited and
divergent assembly of pyrazolones and pyrazolines under metal- much remains to be explored.8 In addition, the cyclization of β,γ-
free conditions is presented. This divergent synthetic strategy was unsaturated hydrazones to deliver the functionalized pyrazolines
achieved by controlling the reaction atmosphere. A number of and pyridazine derivatives has been successfully developed,
pyrazolines were obtained via 5-exo-trig cyclization when the however, the transformation of β,γ-unsaturated hydrazones for the
reaction was performed under N2. Whereas when the reaction construction of pyrazolones via the cleavage of the C=C double
was conducted under O2, diverse functionalized pyrazolones were bond has never been documented so far. Herein, in this paper, we
achieved via oxidative cleavage of the C=C double bond.
disclose an O2-controlled divergent synthetic strategy to streamline
synthesis of pyrazolones and pyrazolines via metal-free cyclization
of β,γ-unsaturated hydrazones (Scheme 1b).
N-centered radicals are eminent intermediates in organic
synthesis which can be leveraged to drive transformations via
radical-mediated addition/cyclization process.1 In recent years,
direct catalytic transformation of the N-H bond into a N-centered
radical to accomplish novel radical reactions has become
flourishing.2 With respect to green or sustainable chemistry, the
development of metal-free, mild and direct synthetic approaches
for the production and transformation of N-centered radicals is
promising, which provides an attractive platform to assemble a
wide array of nitrogen-containing heterocycles.
a) Previous work: transition-metal-catalyzed cyclization of unsaturated hydrazones
R2
X
N
N
5-exo-trig
R2
R1
NH
X = H, CF3, Ar, Br, OH, NR1R2, etc
[M]
N
R2
R1
M = Cu, Pd,
Ru, etc
N
N
6-endo-trig
N
N
or
R1
R1
b) This work: Metal-free Divergent cyclization of unsaturated hydrazones
Ar
Pyrazoline and pyrazolone derivatives have been widely
represented in pharmaceutical chemistry and bioorganic chemistry,
which also served as versatile building blocks in organic synthesis.3
The straightforward cyclization/difunctionalization of β,γ-
unsaturated hydrazones4 has emerged as an attractive method to
forge pyrazoline and pyrazolone scaffolds. In recent years, myriad
publications have presented for the utilization of β,γ-unsaturated
hydrazones as fascinating synthons, enabling to accomplish a range
of structurally diverse synthetic transformations.5-8 Up to date,
transition-metal-catalyzed 5-exo-trig5a-5d,6,7a,7b and 6-endo-trig5f-5h,7c
cyclization reaction of β,γ-unsaturated hydrazones are dominant for
transformation of β,γ-unsaturated hydrazones (Scheme 1a). The
N
N
O
Ar
TBHP, O2
Ar
NH
N
Ar
Metal
N
N
Ar
TBHP, N2
Ar
Scheme 1. Cyclization reactions of β,γ-unsaturated hydrazones
To commence our investigation, 1-(2,2-dimethyl-1-phenylbut-3-
en-1-ylidene)-2-phenylhydrazine (1a) was selected as the
benchmark substrate. When the reaction was carried out under O2
atmosphere by using TBHP as oxidant, the product 4,4-dimethyl-
2,5-diphenyl-2,4-dihydro-3H-pyrazol-3-one (2a) was obtained in
85% yield via oxidative cleavage of the C=C double bond (Table 1,
entry 1), which was attested to be the optimal conditions. The yield
of 2a was sharply decreased when other oxidants were used
instead of TBHP (Table 1, entries 2-4). We also screened a sequence
of solvents (Table 1, entries 5-9). However, only marginal
improvements were achieved and it turned out that CH3CN was the
best reaction medium for the assembly of pyrazolones. When the
reaction was performed without TBHP, no desired product 2a was
aInstitute of Next Generation Matter Transformation, College of Materials Science
& Engineering and College of Chemical Engineering at Huaqiao University, 668
Jimei Blvd, Xiamen, Fujian, 361021, P. R. China
.bKey Laboratory for Organic Synthesis and Function Discovery, Fuzhou Province
University, College of Chemistry at Fuzhou University, Fuzhou 350108, P. R. China.
Email: qsong@hqu.edu.cn; fax: 86-592-6162990;
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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obtained (Table 1, entry 10). The yield of 2a was slightly decreased having different electronic properties on the ArV2iewwAretircele Ownlienlel
DOI: 10.1039/C9CC04039K
to 62% when the model reaction proceeded under air atmosphere compatible in this metal-free transformation, affording the targeted
(Table 1, entry 11). To our surprise and delight, when the reaction pyrazolones in 47%-73% yields (2m−2t). The heterocyclic hydrazone,
was conducted under an inert atmosphere, no desired 2a was such as (E)-1-(2,2-dimethyl-1-(thiophen-2-yl)but-3-en-1-ylidene)-2-
detected and 4,4,5-trimethyl-1,3-diphenyl-4,5-dihydro-1H-pyrazole phenylhydrazine 1u, could also be engaged in this reaction and the
3a was isolated in 60% yield (Table 1, entry 12). After a battery of expected 2u could be isolated in 58% yield. Gratifyingly, this
reaction parameters screening, a decent yield of 3a was achieved in reaction could be readily scaled up to 4 mmol without significant
79% by using nButyl ether as solvent (Table 1, entry 13).
loss of the efficiency.
Table 1. Screening of the Reaction Conditions
Scheme 2. Substrate Scope for the Synthesis of Various Pyrazolones
Ar1
NH
Ar1
N
Ph
Ph
N
Ph
N
NH
N
N
N
TBHP (1.0 equiv)
N
O
N
TBHP, CH3CN
O
Ph
Ar2
CH3CN, O2 (ballon)
80 oC, 10 h
80 oC, O2 (balloon)
Ar2
Ph
Ph
2
1
2a
1a
3a
2a
F
Cl
entrya
Variation from the standard conditions
yield of
(%)
1
2
3
none
85
N
N
N
N
N
DTBP instead of TBHP
NHPI instead of TBHP
trace
trace
<10
36
N
O
O
O
4
5
6
7
8
H2O2 instead of TBHP
EtOH instead of CH3CN
1,4-Dioxane instead of CH3CN
PhMe instead of CH3CN
DMF instead of CH3CN
2a, 85% (65%)a
Br
2b, 65%
2c, 83%
X-ray of 2c
Me
CF3
NO2
43
38
<10
N
N
N
N
N
N
N
N
9
DMSO instead of CH3CN
without TBHP
<10
N.R.
62
O
O
O
O
10
11
12
13
under air
under N2
2d, 70%
2e, 70%
2f, 51%
2g, 46%
(0) (60)b
(0) (79)b
F
nButyl ether instead of CH3CN, under N2
Br
Cl
a
Reaction conditions: (0.2 mmol), TBHP (1 equiv), CH3CN (2 mL), 80 oC,
1
F
N
N
N
N
N
N
O2 (balloon), 10 h. The yields of the isolated products are given. b the
N
N
O
O
O
O
3a
isolated yield of
.
Having identified the optimal reaction conditions, the substrate
scope for this metal-free cyclization of unsaturated hydrazones to
assemble the pyrazolones via oxidative cleavage of the C=C double
bond was investigated (Scheme 2). Halo-substituted unsaturated
hydrazones (1b-1d) were proved to be good candidates, delivering
the desired products (2b-2d) in 65%, 83% and 70% yield,
respectively. The structure of 2c was precisely confirmed by X-ray
single crystal diffraction.9 Similar successful transformations were
also gained for hydrazones bearing electron-withdrawing groups
(CF3 and NO2), enabling the production of the corresponding
pyrazolones 2e and 2f in decent yields. To our surprise, when 1f was
subjected to this oxidative conditions, 5-hydroxy-4,4-dimethyl-1-(4-
2h, 77%
Me
2i, 50%
2j, 75%
2k, 44%
Me
N
N
N
N
N
N
N
N
O
O
O
O
iPr
MeO
Ph
2o, 47%
2n, 64%
2l, 53%
2m, 55%
N
N
N
N
N
N
N
N
O
O
O
O
F3C
Me
2p, 67%
OMe
2q, 61%
F
nitrophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-5-carbaldehyde
4
2r, 68%
2s, 57%
was also obtained in 15% yield (eq 1), the structure of which was
definitely affirmed X-ray diffraction analysis. Compared with the
electron-withdrawing groups substituted hydrazones, the
hydrazones installed the electron-donating groups on the aromatic
ring demonstrated inferior reactivity, rendering the product 2g in
46% yield. To our delight, sterically demanding 1-(2,2-dimethyl-1-
phenylbut-3-en-1-ylidene)-2-(naphthalen-2-yl)hydrazine 1h could
also work smoothly under the identified conditions, and produced
the desired pyrazolone 1h in 77% yield. In addition to para-position
substituted hydrazones, ortho- and meta-position as well as di-
substituted hydrazones were also good substrates in this
transformation, providing the targeted pyrazolones 2i-2l in 44%-
75% yields. Subsequently, we tested a round of hydrazones (1m-1u)
derived from different unsaturated ketones. A strand of hydrazones
N
N
N
N
O
O
S
Cl
2t, 73%
2u, 58%
Reaction conditions: (0.2 mmol), TBHP (1 equiv), CH3CN (2 mL), 80 oC, O2 (balloon), 10 h. The
yields of the isolated products are given. a 4 mmol scale.
1
NO2
NO2
TBHP (1.0 equiv)
N
N
2f
+
OH
CHO
(eq 1)
NH
CH3CN, O2 (ballon)
80 oC, 10 h
N
51%
Ph
Ph
4, 15%
X-ray of 4
1f
2 | J. Name., 2012, 00, 1-3
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As showcased in Table 1 entry 13, when the reaction was was carried out under N2 atmosphere (Scheme 5b), VwiehwicAhrticOle2Ownlianes
DOI: 10.1039/C9CC04039K
performed under an inert atmosphere, the 5-methyl pyrazoline was prerequisite for cleavage of the C=C double bond to assemble
obtained. We then turned our attention to explore the scope for pyrazolones. When 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)
the assembly of pyrazolines. As described in Scheme 3, the was served as radical scavenger underlying the established
unsaturated hydrazones bearing electron-donating groups and conditions, this 5-exo-trig cyclization was seriously restrained and
electron-withdrawing groups were both amenable to this the radical addition product 5 was detected by 1H NMR (Scheme 5c),
transformation, enabling to provide the pyrazolines 3a-3e in 63%- which manifested that a radical-type reaction might be involved in
83% yields under the meta-free conditions. The treatment of halo- this meta-free cyclization. To notarize the origination of the
substituted hydrazones for this 5-exo-trig cyclization was also carbonyl oxygen atom of the targeted pyrazolones, isotope labeling
successful, delivering the products 3f and 3g in 68% and 60 % yield, experiments were executed. When the reaction proceeded under
respectively.
18O2, 41% of 18O-labeled product 2a was observed (Scheme 5d). And
29% of 18O-labeled product 2a was also detected when the reaction
was carried out with 10 equivalents of H218O under O2 atmosphere
(Scheme 5e). Based on the above 18O-labeled experiments, the
oxygen atom in the desired pyrazolones might come from both the
water and O2.
Scheme 3. Substrate Scope for the Synthesis of Pyrazolines
Ar
Ar
N
NH
N
N
TBHP (1.0 equiv)
80 oC, 10 h
nButyl ether, N2
Ar
Ar
1
3
Control experiments:
Ph
N
N
N
N
N
N
N
N
N
H
N
Without TBHP
No Reaction
MeO
(a)
Ph
standard conditions
F3C
MeO
1a
N
3a, 79% (70%)a
3b, 63%
3c, 66%
3d, 76%
Cl
Ph
Br
Ph
N
Ph
N
N
N
H
N
Under N2
O
+
N
N
(b)
Ph
Ph
Ph
standard conditions
N
N
N
N
1a
3a, 60%
Ph
2a, 0%
iPr
Radical-scavenging experiment:
x-ray of 3f
3e, 83%
3f, 68%
3g, 60%
Ph
Ph
N
N
N
Reaction conditions: (0.2 mmol), TBHP (1 equiv), nButyl ether (2 mL), 80 oC, N2, 10 h. The
yields of the isolated products are given. a 4 mmol scale.
N
O N
3 equiv TEMPO
1
N
N
H
O
(c)
standard conditions
Ph
Ph
Ph
In order to broaden the substrate scale, we also investigated the
unsaturated alkynyl hydrazones. As shown in Scheme 4, a number
of pyrazolones could be achieved in moderate yields via oxidative
cleavage of the CC triple bond.
5 (detected by 1H NMR)
2a, 11%
18O
1a
Labeling experiments:
Ph
N
TBHP (1.0 equiv)
anhydrous CH3CN
Ph
N
N
H
(d)
N
Ph
Ph
18O
2 , 80 oC, 10 h
18O 2a 16O 2a
Scheme 4. Substrate Scope for the Synthesis of Pyrazolones via
-
:
-
= 41:59
1a
18O
Oxidative Cleavage of the CC triple bond.
Ph
N
Ar
N
TBHP (1.0 equiv)
18O
(10 equiv)
Ph
N
H
N
Ar
(e)
N
N
N NH
H
O2
,
TBHP (1.0 equiv)
2
Ph
O
Ph
18O 2a 16O 2a
= 29:71
Ar
anhydrous CH3CN
CH3CN, O2 (ballon)
80 oC, 10 h
Ar
1a
-
:
-
Scheme 5. Mechanism studies
2
1'
Cl
Me
O
On the basis of the primary mechanism studies, a tentative
reaction mechanism for this divergent transformation is delineated
in Scheme 6. First, unsaturated hydrazone 1 is abstracted a
hydrogen atom by the TBHP to afford the N-center radical A,8c
generating the HO· and tBuOH. Subsequently, the N-center radical A
undergoes the 5-exo-trig cyclization to provide the radical
intermediate B.8c When the reaction is performed without O2, the
transfer of a hydrogen atom to radical intermediate B delivers the
pyrazoline 3.7b When the reaction proceeded under O2, the radical
intermediate B is captured by O2 to form the hydroperoxide radical
species C,5e,10,11,12,13 which goes through the 1,4-H shift to render
the C-center radical D.5e The intermediate D is oxidized to give the
carbocation intermediate E, which undergoes the attack of water to
generate the compound F. As one alternative pathway, the
compound F can be formed by the coupling with C-center radical D
and the hydroxyl radical. At this point, O-O bond cleavage of
compound F renders the radical intermediate G, which successively
suffers from the β-fragmentation, leading to the formation of
Br
N
N
N
N
N
N
N
N
O
O
O
2a, 46%
2c, 32%
2g, 40%
2i, 35%
Reaction conditions: (0.2 mmol), TBHP (1 equiv), CH3CN (2 mL), 80 oC, O2 (balloon), 10
h. The yields of the isolated products are given.
1
Subsequently, we attempted to shed light on the reaction
mechanism for this divergent transformation. Several control
experiments were conducted preferentially. When the reaction was
performed in the absence of TBHP, the starting material stayed
intact (Scheme 5a), which indicated that the oxidant was obligatory
for this 5-exo-trig cyclization. No pyrazolone 2a was detected and
pyrazoline 3a was achieved as the major product when the reaction
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Traynelis and D. Liotta, J. Med. Chem. 2013, 56, 6434; (c) X.
Liu, B. Ruan, J. Li, F.Chen, B. Song, H.DZOhIu: 1,0P.1.0B3Vh9i/aeCwd9uACrrtCiyc0lea4On0nd3l9inJKe.
Zhao, Mini-Rev. Med. Chem., 2011, 11, 771; (d) M. Kashiwa,
Y. Kuwata, M. Sonoda and S. Tanimori, Tetrahedron., 2016,
72, 304; (e) K. Silver and D. Soderlund, Pestic. Biochem.
Physiol., 2005, 81, 136.
intermediate H. Abstraction of a hydrogen atom of intermediate H
furnishes the pyrazolone 2. On the other hand, the radical
intermediate I is formed by hydrogen atoms abstraction from
compound F.Subsequently, β-fragmentation of intermediate I
generates the compound 4.
H
Ar
4
5
For some reviews on hydrazones, see: (a) S. Kobayashi, Y.
Mori, J. Fossey and M. Salter, Chem. Rev., 2011, 111, 2626;
(b) Y. Xia and J. Wang, Chem. Soc. Rev., 2017, 46, 2306.
Some examples for Cu-catalyzed transformations of β,γ-
unsaturated hydrazones, see: (a) B. Chang, Y. Su, D. Huang, K.
Wang, W. Zhang, Y. Shi, X. Zhang and Y. Hu, J. Org. Chem.,
2018, 83, 4365; (b) M. Chen, L. Wang, P. Ren, X. Hou, Z. Fang,
M. Han and W. Li, Org. Lett., 2018, 20, 510; (c) R. Liu, Z.
Wang, B. Wei, J. Zhang, B. Zhou and B. Han, Org. Lett. 2018,
20, 4183; (d) L. Wang, P. Ren, L. Qi, M. Chen, Y. Lu, J. Zhao, R.
Liu, J. Chen and W. Li, Org. Lett., 2018, 20, 4411; (e) F.
Pünner, Y. Sohtome and M. Sodeoka, Chem. Commun., 2016,
52, 14093; (f) Z. Fan, Z. Pan, L. Huang and J. Cheng, J. Org.
Chem., 2019, 84, 4236; (g) Y. Guo, M. Zhao, Z. Ren and Z.
Guan, Org. Lett., 2018, 20, 3337; (h) D. Jiang, J. Hu, W. Hao, S.
Wang, S. Tu and B. Jiang, Org. Chem. Front., 2018, 5, 189; (i)
M. Ke and Q. Song, J. Org. Chem., 2016, 81, 3654.
Some examples for Pd-catalyzed transformations of β,γ-
unsaturated hydrazones, see: (a) L. Li, P. Liu, Y. Su and H.
Huang, Org. Lett., 2016, 18, 5736−5739; (b) M. Yang, D. Yan,
Q. Zhao, J. Chen and W. Xiao, Org. Lett., 2017, 19, 5208; (c) J.
Chen, M. Yang, J. Chen and W. Xiao, Org. Lett., 2018, 20,
3314.
Some examples for visible-light promoted transformations of
β,γ-unsaturated hydrazones, see: (a) Q. Wei, J. Chen, X. Hu, X.
Yang, B. Lu and W. Xiao, Org. Lett., 2015, 17, 4464; (b) X. Hu,
J. Chen, Q. Wei, F. Liu, Q. Deng, A. Beauchemin and W. Xiao,
Angew. Chem. Int. Ed., 2014, 53, 12163; (c) X. Hu, X. Qi, J.
Chen, Q. Zhao, Q. Wei, Y. Lan and W. Xiao, Nat. Commun.,
2016, 7, 11188; (d) J. Yu and C. Cai, Eur. J. Org. Chem., 2017,
40, 6008; (e) T. Zhang, Y. Meng, J. Lu, Y. Yang, G. Li and C.
Zhu, Adv. Synth. Catal., 2018, 360, 3063.
Ar
OH
N
N
N
Ar
N
N
N
O
O
Ph
Ph
Ph
1
2
4
TBHP
NO2
Ar =
OH + tBuOH
[O]
-fragmentation
OH
N
Ar
N
Ar
N
O
N
Ar
N
N
OH
Ph
OH
Ph
Ph
A
I
H
H2O
OH
-fragmentation
H-atom abstraction
Ar
N
OH
Ar
N
Ar
N
O
O
N
O-O bond cleavage
Ph
N
N
Ph
OH
OH
Ph
B
OH
F
G
O2
OH
H-atom abstraction
N2
Ph
H2O
HO
O
O
OH
Ar
O
Ar
Ar
N
N
O
1,4-H shift
[O]
N
N
N
N
6
7
N
N
Ph
Ph
Ph
Ph
3
C
D
E
Scheme 6. Proposed Reaction Mechanism
In summary, facile and metal-free protocol has been
a
developed for the divergent assembly of pyrazolones and
pyrazolines, in which a strand of pyrazolones and pyrazolines were
achieved in decent yields via 5-exo-trig cyclization of unsaturated
hydrazones. The mechanism studies indicate that TBHP is essential
for this divergent transformation and O2 is requisite for cleavage of
the C=C double bond to assemble pyrazolones. Further studies
towards the mechanism details and synthetic applications of this
divergent transformation are underway in our laboratory.
This research was financially supported the National Natural
Science Foundation (21772046) and the Natural Science Foundation
of Fujian Province (2016J01064) are gratefully acknowledged. We
also thank Instrumental Analysis Center of Huaqiao University for
analysis support. X. L. thanks for Subsidized Project for Cultivating
Postgraduates’ Innovative Ability in Scientific Research of Huaqiao
University.
8
9
Some examples for metal-free transformations of β,γ-
unsaturated hydrazones, see: (a) X. Hu, J. Chen, Q. Wei, F. Liu,
Q. Deng, Y. Zou and W. Xiao, Eur. J. Org. Chem., 2014, 15,
3082; (b) J. Zhao, M. Jiang and J. Liu, Org. Chem. Front., 2018,
5, 1155; (c) X. Duan, X. Yang, P. Jia, M. Zhang and B. Han, Org.
Lett., 2015, 17, 6022
CCDC-1916783 (2c), CCDC-1876777 (2F) and CCDC-1916788
(3f) contain the supplementary crystallographic data for this
paper.
10 R. Lin, F. Chen and N. Jiao, Org. Lett., 2012, 14, 4158.
11 X. Peng, D. Wei, W. Han, F. Chen, W. Yu and B. Han, ACS
Catal., 2017, 7, 7830.
12 M. Zhou, M. Chen, Y. Zhou, K. Yang, J. Su, J. Du and Qiuling
Song, Org. Lett., 2015, 17, 1786.
13 Y. Zhou, M. Zhou, M. Chen, J. Su, J. Du and Q. Song, RSC Adv.,
2015, 5, 103977.
Notes and references
1
2
For some reviews on N-centered radicals, see: (a) J. Chen, X.
Hu, L. Lu, and W. Xiao, Acc. Chem. Res., 2016, 49, 1911; (b) J.
Chen, X. Hu, L. Lu and W. Xiao, Chem. Soc. Rev., 2016, 45,
2044; (c) M. Kärkäs, ACS Catal., 2017, 7, 4999; (d) J. Luo and
W. Wei, Adv. Synth. Catal., 2018, 360, 2076.
(a) X. Duan, N. Zhou, R. Fang, X. Yang, W. Yu and B. Han,
Angew. Chem. Int. Ed., 2014, 53, 3158; (b) J. Kemper, A.
Studer, Angew. Chem. Int. Ed., 2005, 44, 4914; (c) X. Yu, J.
Chen, P. Wang, M. Yang, D. Liang and W. Xiao, Angew. Chem.
Int. Ed., 2018, 57, 738; (d) Y. Li, R. Wang, T. Wang, X. Cheng,
X. Zhou, F. Fei and X. Wang, Angew. Chem. Int. Ed., 2017, 56,
15436; (e) S. Gao and M. Niggemann, Adv. Synth. Catal.,
2019, 361, 1549; (f) L. Zhang, M. Zhu, S. Ni, L. Wen and M. Li,
ACS Catal., 2019, 9, 1680.
3
(a) M. Abdel-Halim,B. Diesel, A. Kiemer, A. Abadi, R.
Hartmann and M. Engel, J. Med. Chem., 2014, 57, 6513; (b) T.
Acker, A. Khatri, K, Vance, C. Slabber, J. Bacsa, J. Snyder, S.
4 | J. Name., 2012, 00, 1-3
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