An innovative synthesis of tertiary hydroxyl thieno[2,3-d]pyrimidinone skeleton: Natural-like product from the tandem reaction of o-aminothienonitrile and carbonyl compound

Article abstract of DOI:10.1016/j.tetlet.2016.04.088

A straightforward base accelerant tandem protocol for the synthesis of the tertiary hydroxyl natural-like thieno[2,3-d]pyrimidinone skeleton was developed from the cyclocondensation of o-aminothienonitrile and carbonyl compound. The reaction process includes PDF conversion and photo-catalytic oxygenation. This synthetic strategy offers an alternative method for regioselective construction of tertiary hydroxylated thieno[2,3-d]pyrimidinone architectures with kinetic, thermodynamic control, and six-member ring effect.

Full text of DOI:10.1016/j.tetlet.2016.04.088

Tetrahedron Letters 57 (2016) 2455–2461
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Tetrahedron Letters
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An innovative synthesis of tertiary hydroxyl thieno[2,3-d]
pyrimidinone skeleton: natural-like product from the tandem
reaction of o-aminothienonitrile and carbonyl compound
a
a
b
a
a
a,
⇑
Junjuan Yang , Daxin Shi , Pengfei Hao , Deli Yang , Qi Zhang , Jiarong Li
a
School of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, China
School of Chemistry & Material Science, Shanxi Normal University, Linfen 041004, PR China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A straightforward base accelerant tandem protocol for the synthesis of the tertiary hydroxyl natural-like
thieno[2,3-d]pyrimidinone skeleton was developed from the cyclocondensation of o-aminothienonitrile
and carbonyl compound. The reaction process includes PDF conversion and photo-catalytic oxygenation.
This synthetic strategy offers an alternative method for regioselective construction of tertiary hydroxy-
lated thieno[2,3-d]pyrimidinone architectures with kinetic, thermodynamic control, and six-member
ring effect.
Received 28 January 2016
Revised 20 April 2016
Accepted 22 April 2016
Available online 23 April 2016
Keywords:
Tertiary hydroxylated thieno[2,3-d]
pyrimidinone
Ó 2016 Elsevier Ltd. All rights reserved.
o-Aminothienonitrile
Carbonyl compound
Photo-catalytic oxygenation
PDF conversion
Introduction
and also serves as fundamental building blocks for various applica-
tions in organic synthesis. Embedding an extra tertiary hydroxyl
9
The thienopyrimidinone nucleus is a basic structural feature
which exists in many biologically active, pharmaceutical relevant
natural products and synthetic analogues (Fig. 1, red). Substituted
thienopyrimidinones have been assigned as privileged structures
in drugs because of the remarkable pharmacological activities
group on the NPs/NLPs could endow their outstanding bioactivity
and metabolic stability.
1
0
With respect to the valuable tertiary hydroxyl group and bioac-
tivity of thieno[2,3-d]pyrimidinone, it was necessary to construct
the novel tertiary hydroxyl thieno[2,3-d]pyrimidinone skeleton
compound. The traditional synthesis of tertiary hydroxyl NLPs is a
two step process: first, to prepare the NLPs skeleton compound;
and second to modify the tertiary hydroxyl group by microbial
including anti-inflammation, anti-malarial,2 anti-plasmodial,
1
3
4
and anti-cancer. The traditional synthetic approach toward
thieno[2,3-d]pyrimidinone employs the condensation of ketones
with o-aminothiophene dicarboxamide, which was derived by
hydrolysis from the corresponding o-aminonitriles.5 However,
these synthetic methods suffer from significant limitations such
as multistep sequences, time-consuming process, and use of toxic
reagents. In recent years, the use of green procedure in one pot
in place of traditional synthetic routes has attracted considerable
attention. To improve the desired properties,7 the intentional
introduction of a hydroxyl group on NPs or the biologically active
natural-like products (NLPs) have been considered as one of the
1
1
12
14
epoxidation, in vivo oxidation of secondary hydroxyl series,
13
alkylation of carbonyl compound, reaction with a-furyllithium,
asymmetric Michael addition,
8
,15
and photo-catalytic oxygena-
1
6
tion. To the best of our knowledge, there is rare study on the syn-
thesis of the tertiary hydroxyl NLPs derivatives via a one-pot
tandem approach. Inspired by the tertiary hydroxyl thieno[2,3-d]
pyrimidinone potential bioactivity and continuing our interest in
the construction of significant heterocyclic skeletons with
o-aminonitriles as starting material, herein we are glad to report
the discovery of tertiary hydroxyl thieno[2,3-d]pyrimidinone
derivatives synthesized via a one-pot tandem approach of PDF reac-
6
8
most facile strategies in pharmaceutical research (Fig. 1, blue).
Noteworthily, optically active tertiary hydroxyl chirality com-
pound is a structural motif in numerous biological compounds
1
7
tion and photo-catalytic oxygenation from o-aminothienonitrile
and carbonyl compound.
⇑
Corresponding author. Tel./fax: +86 010 68918012.
E-mail address: jrli@bit.edu.cn (J. Li).
http://dx.doi.org/10.1016/j.tetlet.2016.04.088
040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
0

2
456
J. Yang et al. / Tetrahedron Letters 57 (2016) 2455–2461
Figure 1. Selected examples of biologically active thienopyrimidinones, tertiary hydroxyl thiophene containing compounds, and our work.
O
R2
O
NH2
N
R
2
R2
CN
NH
R
3
R
4
accelerant
T, t
R
1
+
+
R1
R
1
NH
2
R3
HO
S
N
R
4
S
S
R4
1
2
3
R
4
3
Scheme 1. The divergent conversion from of o-aminothienonitrile 1 and ketone 2.
Table 1
Optimization of reaction conditions
a
O
O
NH2
N
CN
NH
+
accelerant
T, t
+
NH
2
HO
S
N
S
S
1a
2a
3a
4a
Entry
Accelerant(1 equiv)
Solvent
Temp (°C)
Time(h)
Yieldb (%)
3a
4a
1
2
3
4
5
6
7
8
9
TsOH
PPA
2a
2a
2a
2a
2a
2a
2a
EtOH
MeCN
DMF
Toluene
2a
2a
2a
2a
2a
120
120
120
120
120
120
120
120
120
120
120
40
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
—c
—
46.8
65.5
65.4
63.5
25.2
23.3
20.6
10.9
13.5
11.6
20.6
18.4
18.0
19.5
19.1
21.8
AlCl
ZnCl
3
Trace
Trace
35.0
45.9
65.7
35.5
12.7
15.4
12.3
18.3
27.5
35.8
58.6
48.1
2
NaOH
MeONa
EtONa
EtONa
EtONa
EtONa
EtONa
EtONa
EtONa
EtONa
EtONa
EtONa
10
11
12
13
14
15
16
60
80
100
140
a
b
c
Reactions conditions: 1a (1 mmol), 2a (1.5 mmol), and accelerant (1 equiv) in solvent (3.0 mL) with UV lamp irradiation.
Isolated yields.
The target product was not found by TLC.

J. Yang et al. / Tetrahedron Letters 57 (2016) 2455–2461
2457
Table 2
a
Synthesis of hydroxylated thiophene derivatives 3
O
N
R
2
O
NH
2
CN
R
2
R
2
NH
R
R
3
4
EtONa, air
R
1
+
R
4
+
R
1
R
1
NH
2
R3
o
HO
S
R
4
S
hv, 120 C, 3.0 h
S
N
1
2
3
R
3
4
Entry
R
1
, R
2
R
3
, R
4
Product
Yieldb (%)
Product
Yieldc (%)
1
2
3
4
5
6
7
8
9
R
R
R
R
R
R
R
R
R
R
R
1
1
1
1
1
1
1
1
1
1
1
+ R
+ R
+ R
+ R
+ R
+ R
+ R
+ R
+ R
+ R
+ R
2
2
2
2
2
2
2
2
2
2
2
= (CH
= (CH
= (CH
= (CH
= (CH
= (CH
= (CH
= (CH
= (CH
= (CH
= (CH
2
2
2
2
2
2
2
2
2
2
2
)
3
3
3
4
4
4
5
5
5
4
4
R
R
R
R
R
R
R
R
R
R
R
3
3
3
3
3
3
3
3
3
4
3
+ R
+ R
+ R
+ R
+ R
+ R
+ R
+ R
+ R
4
4
4
4
4
4
4
4
4
= (CH
= (CH
= (CH
= (CH
= (CH
= (CH
= (CH
= (CH
= (CH
2
2
2
2
2
2
2
2
2
)
)
)
)
)
)
)
)
)
3
4
5
3
4
5
3
4
5
—d
—
—
—
3a
—
—
—
—
—
—
—
4b
4c
4d
4e
4a
4f
4g
4h
4i
Trace
33.5
45.2
Trace
20.6
58.9
Trace
45.1
54.3
26.3
22.1
)
)
)
)
)
)
)
)
)
)
Trace
Trace
—
65.7
Trace
—
Trace
Trace
Trace
Trace
1
1
0
1
= H, R
= CH ,R
3
= CH
= CH
3
4j
4k
3
4
3
a
b
c
Reactions conditions: 1 (1 mmol) and EtONa (1 equiv) in corresponding carbonyl compounds 2 (3.0 mL) with UV lamp irradiation.
Isolated yields.
Isolated yields or TLC detection yields.
The products 3 were not found by TLC or MS.
d
Results and discussion
(entry 5). When the cyclopentanone was tested, no transformation
of tertiary hydroxyl derivatives and 4b, 4e, and 4g occurred
(entries 1, 4 and 7). Additionally, the products obtained were 4c,
4d, 4f, and 4h–k but not the corresponding tertiary hydroxyl
thieno[2,3-d]pyrimidinone when other ketones were employed
(entries 2, 3, 6, 8–11). Evidently, only the cyclocondensation of
2-amino-4,5,6,7-tetrahydrobenzo [b]thiophene-3-carbonitrile 1a
and cyclohexanone 2a provided the expected tertiary hydroxyl
derivative 3 with good yields perhaps for reasons of steric
hindrance and ring tension.
Based on the unique phenomenon, we turned our attention to
investigating the scope of substituted 2-amino-4,5,6,7-tetrahydro-
benzo[b]thiophene-3-carbonitrile 1 and cyclohexanone derivatives
2 for preparing the tertiary hydroxylated thieno[2,3-d]pyrimidi-
none derivatives 3. The results showed that the reactions were
When the reaction of o-aminothienonitrile 1 and ketone 2 was
carried out at 120 °C in the presence of EtONa (Scheme 1), the
expected fused heterocyclic derivatives containing a tertiary
hydroxyl moiety of thieno[2,3-d]pyrimidinone 3 was obtained.
Additionally, a dehydration product, thieno[2,3-b]pyridines 4,
was also obtained, with its formation possibly based on a Friedlän-
1
7
der condensation.
Initially, the reaction of 2-amino-4,5,6,7-tetrahydrobenzo-[b]
thiophene-3-carbonitrile 1a and cyclohexanone 2a was chosen as
the model substrate to optimize the conditions (Table 1). Various
accelerants such as BrØnsted acids, Lewis acids, and base were
evaluated for the reaction and the results showed that accelerant
was a key factor to control the reaction route. The data indicated
that only a single product 4a was obtained in the presence of
BrØnsted acids of TsOH and PPA (entry 1 and 2), while only a trace
amount of product 3a was observed by thin layer chromatography
tolerated when 2 bear an electron-donating group (R
4-Me or 4-Et) (Table 3, entries 2–4 vs 1). Thereafter, the sub-
stituents (R = Me) on 1 were investigated and the results showed
2
= 3-Me,
1
(
TLC) when the Lewis acid of AlCl
3
and ZnCl
2
were used (entry 3
that the corresponding derivatives 3 were also obtained (Table 3,
and 4). The results from Table 1 (entries 5–7) showed slightly
decreasing yields of compound 4a and significantly increasing
yields of compound 3a because of changing the base accelerant
from NaOH to NaOMe to NaOEt, and strong base was beneficial
to push the reaction forward. Similar reactions were then
attempted in different solvents and the results showed that the
cyclohexanone itself was the medium of choice for the formation
of 3a (entries 7–11). Additionally, the yield of compound 3 was
increased with the rasing of temperature, but 120 °C was the better
selection (entries 12–16). It was worth mentioning that the prod-
ucts 3 could be isolated from the reaction mixture by filtration.
Therefore, it can be inferred that the preparation of 3a was a kinet-
ically controlled reaction and the optimum reaction condition was
reflux for 3.0 h in the presence of EtONa with cyclohexanone itself
as medium with UV lamp irradiation in air.
entries 5 and 9 vs 1). And the reactions were also extended to
the interactive variations of R and R (Table 3, entries 6–8 and
1 2
10–13). However, the correlation between the products and the
molecular structures can currently be described only empirically.
Overall, the hydroxylated thieno[2,3-d]pyrimidinone derivatives
3
were formed in
a one-pot procedure while substituted
2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile
1
1
8
and cyclohexanone derivatives 2 used as the substrates perhaps
for the charge effect, thermodynamic stability of six-member ring,
1
9
and low strain of cyclohexane collective effect.
The chemical structures of target compounds 3 were fully char-
1
13
acterized by IR, H NMR, C NMR, and HRMS, while product 3a
and 3b were unequivocally confirmed by X-ray diffraction analysis
(Fig. 2). Take crystal data of 3a as an example, the thieno[2,3-d]
pyrimidinone skeleton was nearly coplanar while the six-
membered rings of C(3)AC(4)AC(5)AC(6)AC(7)AC(8) and
C(10)AC(11)AC(12)AC(13)AC(14)AC(15) were present in chair
conformations. In addition, the structure confirmed there was a
stereogenic center at C(4) with a tertiary hydroxyl group. Further-
more, the C(9)AN(2) (1.3412) and C(1)@N(1) (1.2761) bonds were
In order to apply this reaction to a library synthesis, a series of
o-aminothienonitrile 1 and ketone 2 were employed. Astonish-
ingly, as shown in Table 2, only the reaction of 2-amino-4,5,6,
7
-tetrahydro-benzo[b]thiophene-3-carbonitrile 1a and cyclohex-
anone 2a provided the expected tertiary hydroxyl derivative 3a

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J. Yang et al. / Tetrahedron Letters 57 (2016) 2455–2461
Table 3
Synthesis of six-membered hydroxylated fused thiophene derivatives 3a
O
O
N
R1
CN
EtONa, air
hv, 120 oC, 3.0 h
R1
NH
+
*
HO
*
NH2
S
S
R2
R2
1
2
3
Entry
1
R
1
R
2
Product
drb
—
Yieldc (%)
65.7
CN
O
O
O
O
O
NH
*
NH2
S
S
S
S
HO
1
1
1
1
a
a
a
a
S
2
a
N
O
3
a
CN
NH
*
*
2
3
NH2
>25:1
73.5
60.2
HO
HO
HO
2
b
S
N
O
3
b
CN
NH
NH
*
NH2
—
S
S
N
O
2
c
3c
CN
*
NH2
4
5
6
7
—
80.1
57.8
66.3
57.6
N
O
3
d
2
d
a
CN
O
O
O
O
NH2
NH
S
S
S
*
*
—
1
b
b
b
b
2
HO
HO
HO
HO
S
S
S
N
O
3
e
CN
CN
CN
NH2
NH
*
6:1
1
1
1
2
b
N
O
3
f
NH2
NH
NH
*
—
N
O
2
c
3
g
NH2
8
9
S
*
—
—
75.2
71.5
S
N
2
d
a
3h
CN
O
O
N
NH
*
NH2
S
HO
1
c
S
2
3
i

J. Yang et al. / Tetrahedron Letters 57 (2016) 2455–2461
2459
Table 3 (continued)
Entry
R
1
R
2
Product
drb
Yieldc (%)
CN
CN
O
O
O
NH
*
*
*
10
11
12
13
NH2
>25:1
78.3
72.1
70.8
59.6
S
S
HO
1
1
c
c
S
2
b
N
O
3
j
NH
NH2
—
HO
S
*
N
2
c
3k
CN
O
O
O
NH
*
NH2
>25:1
S
S
HO
HO
1
1
d
d
S
S
2
b
N
O
3
l
CN
NH
*
NH2
—
N
2
c
3m
a
b
c
Reactions conditions: 1 (1 mmol) EtONa (1 equiv) in corresponding ketones 2 (3.0 mL) at 120 °C for 3.0 h with UV lamp irradiation.
Detected by 1H NMR.
Isolated yields.
Well resolved proton signals consistent with the chemical
formulation, shifts, and splitting patterns were observed in the
DMSO-d
of both hydroxyl group and imino group disappeared when the
hydrogen proton exchanged between D O with OH and NH groups
Fig. S1).
One possible mechanistic hypothesis was proposed and
6
solution. However, the proton signal of active hydrogens
2
(
depicted in Scheme 2. Firstly, intermediate 5 was produced by
the addition of the amino group of 1 onto the carbonyl group of
cyclohexanone 2; Then the Pinner reaction (path B) through attack
by the hydroxyl group on the nitrile and subsequent Dimroth rear-
rangement happened with the dehydration reaction (path A). The
pathways are controlled by the collective effect of kinetics, ther-
modynamics, and six-membered ring effect. The initial dehydra-
tion reaction route resulted in the formation of thieno[2,3-b]
pyridines 4 via Friedländer reaction whereas the Pinner reaction
way afforded the thieno[2,3-d]oxazine 6. Subsequently 6 rear-
ranged to the 7 (Dimroth rearrangement) (PDF conversion: a trans-
formation from Pinner to Dimroth rearrangement in the
1
7
Friedländer conditions ). Afterward, product 7 slowly translated
to the hydroxylated target materials 3 via photo-oxygenation.1
In order to study the proposed mechanism and explain the ther-
modynamical favored product 3, we tried to separate the interme-
diate thieno[2,3-d]pyrimidinone 7. Fortunately, 7d was detected
by TLC and isolated by thin-layer chromatography. The structure
of 7d was further confirmed by IR, H NMR, C NMR, and HRMS.
To our delight, a slow transformation of 7d to its hydroxylated
6
derivative 3d occurred when a solution of 7d in DMSO-d in a
6,21
Figure 2. X-ray structures of 3a (up) and 3b (down).
remarkably shorter than the normal bond CAN (1.47) and C@N
1.38), which may be ascribed to the thieno[2,3-d]pyrimidinone
fused-ring as a big -conjugated system. Here, the C(9)AN(2)
1.3412) and C(1)@N(1) (1.2761) bonds were also remarkably
shorter than the corresponding bonds (CAN (1.4293) and C@N
1.3016)) of the thieno[2,3-d]pyrimidinone skeleton without the
1
13
(
p
(
nuclear magnetic resonance tube was irradiated with a 380 nm
1
UV lamp or heated (Fig. 3). Contrasting the H NMR spectra
(
between 7d and 3d revealed that once the transformation
occurred, the chemical shifts of H(a)AN(2) moved to high field
region and, in contrast, H(b)AN(1) moved to low field relative to
the new hydroxyl H(c)AO(1) signal. The conversion was further
confirmed by the appearance of peaks at m/z 305.16844 and
hydroxylated group substitution which are prepared by the
traditional method of aza-Wittig reaction.20 Maybe the shorter
bonds are attributed to the tertiary hydroxyl group electron-
donating inductive effect. The further support was provided by
1
the H NMR titration experiments of 3l at D
2
O-DMSO-d
6
mixtures.
3
21.16355 assignable to 7d and 3d in the ESI-HRMS spectrum

2
460
J. Yang et al. / Tetrahedron Letters 57 (2016) 2455–2461
R1
NH
2
CN
N
R1
R
2
S
R2
S
N
4
R
1
A
2
-H O
CN
NH
Friedlander
O
R
1
R
1
S
R1
O
N
CN
2
NH
1
OH
PDF Conversation
O
+
NH
S
photo-assiant
O
S
N
H
N
H
HO
R2
S
R
2
7
R
2
5
3
R
2
2
B
Dimroth
NH
N
R1
R
1
O
OH
Pinner
S
S
N
H
6
N
H
R
2
R2
Scheme 2. Proposed mechanism for the new conversion.
Figure 3. Part of the 1H NMR spectra (DMSO-d
) of transformation of 7d to 3d.
6
respectively (Fig. S2).22 Furthermore, the product 3d could be
precipitated from the reaction solution via a slowly photo-catalytic
oxygenation with 380 nm UV lamp irradiation. The process
afforded a simple and clean isolation of the product by filtration
and recrystallization without column chromatography. Further-
Conclusions
In summary, we have successfully developed a novel, efficient
tandem procedure for the synthesis of a tertiary hydroxyl natu-
ral-like thieno[2,3-d]pyrimidinone skeleton products 3 from o-
amino-thienonitrile 1 and carbonyl compound 2 in the presence
of the NaOCH CH with UV lamp irradiation. The tandem process
2
more, the control reactions in dark or without O were run, and
the product 3a could not be captured. In the photo-catalytic
oxygenation, singlet oxygen was the oxidative agent generated
by the application of the oxygen.16,23
2
3
includes PDF conversion and photo-oxygenation. The reaction
was shown to have attractive features, including environmentally

J. Yang et al. / Tetrahedron Letters 57 (2016) 2455–2461
2461
friendly conditions, simple, clean isolated processing and large
scale production.
W.; Schmitz, K. R.; Sello, J. K. J. Am. Chem. Soc. 2014, 136, 1922; (d) Yao, C.; Qin,
B.; Tu, S.-J. RSC Adv. 2012, 2, 3759; (e) Ramachandran, G.; Sathiyanarayanan, K.
I. Synth. Commun. 2015, 45, 750.
7
.
.
(a) Ochoa-Villarreal, M.; Howat, S.; Jang, M. O.; Loake, G. J. New Biotechnol.
2015, 32, 581; (b) Alpers, D.; Gallhof, M.; Brasholz, M. Chem. Commun. 2016,
Acknowledgments
1025.
8
(a) Liu, Q.; Qiao, B.; Jiang, Z. Adv. Synth. Catal. 2014, 356, 3777; (b) Yang, Z.; Wu,
Y.; Wu, S. RSC Adv. 2015, 5, 77553.
This work was supported by the grant of Beijing Institute of
Technology (20131042006). We are grateful for analytical help of
Institute of Chemistry, Chinese Academy of Sciences, Beijing
University of Chemical Technology and Peking University.
9. (a) Block, J. H.; Nunes, M. A. J. Org. Chem. 1970, 35, 3456; (b) Kupchan, S. M.;
Block, J. H.; Isenberg, A. C. J. Am. Chem. Soc. 1967, 89, 1189; (c) Yamada, K.;
Takada, S.; Hirata, Y. Tetrahedron 1968, 24, 1267; (d) Pradhan, P.; Gangan, V. D.;
Banerji, A. Spectrosc. Lett. 1997, 30, 1467.
10. (a) Motwani, H. V.; Rosa, M. De; Larhed, M. Eur. J. Med. Chem. 2015, 90, 462; (b)
Probst, N. P.; Haudrechy, A.; Plé, K. J. Org. Chem. 2008, 73, 4338.
Supplementary data
1
1
1. Takahashi, O.; Umezawa, J.; Takagi, M. Tetrahedron Lett. 1989, 30, 1583.
2. (a) Zhu, H. Y.; Desai, J.; Girijavallabhan, V. M. Bioorg. Med. Chem. Lett. 2014, 24,
1228; (b) Kobayashi, M. Tetrahedron 2000, 56, 1661.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.04.
1
3. (a) Wångsell, F.; Russo, F.; Larhed, M. Bioorg. Med. Chem. Lett. 2009, 19, 4711;
(
b) Smirnov, P.; Katan, E.; Marek, I. J. Org. Chem. 2014, 79, 12122; (c) Barnard, K.
0
88.
R.; Shiers, D. W.; Lombardo, D. Solvent Extr. Ion Exch. 2014, 33, 166.
4. Chujo, Y.; Morimoto, M.; Tomita, I. Polym. Bull. 1992, 29, 617.
5. Zhu, T.-S.; Jin, S.-S.; Xu, M.-H. Angew. Chem., Int. Ed. 2012, 51, 780.
6. (a) Vuk, D.; Kikaš, I.; Škori c´ , I. J. Mol. Struct. 2014, 1063, 83; (b) Chen, X.-B.; Liu,
Z.-C.; Lin, J. ACS Sustain. Chem. Eng. 2014, 2, 1155.
7. (a) Li, J.-R.; Zhang, L.-J.; Fan, Y.-Q. Synlett 2008, 233; (b) Yang, L.-P.; Shi, D.-X.;
Li, J.-R. Green Chem. 2012, 14, 945; (c) Yang, J.-J.; Shi, D.-X.; Li, J.-R. Chin. J. Org.
Chem. 2014, 34, 2424.
1
1
1
References and notes
1
.
(a) Endo, Y.; Kawai, K.; Irie, T. Bioorg. Med. Chem. Lett. 2015, 25, 1910; (b)
Modica, M.; Santagati, M.; Mennini, T. J. Med. Chem. 1997, 40, 574; (c) Kawai, K.;
Endo, Y.; Nagata, N. J. Med. Chem. 2014, 57, 9844; (d) Wilding, B.; Faschauner,
S.; Klempier, N. Tetrahedron Lett. 2015, 56, 4486.
1
1
1
2
8. Yang, L.; Li, J.; Chai, H.; Shi, D. Chin. J. Org. Chem. 2013, 31, 443.
9. Bach, R. D.; Dmitrenko, O. J. Am. Chem. Soc. 2006, 128, 4598.
0. Li, R.-K.; Yang, Q.-L.; Huan, N.-Y.; Cheng, C.; Liu, M. G. Chin. J. Struct. Chem. 2015,
2
3
.
.
Cohen, A.; Suzanne, P.; Azas, N. Eur. J. Med. Chem. 2015, 95, 16.
(a) González Cabrera, D.; Le Manach, C.; Chibale, K. J. Med. Chem. 2014, 57,
1
014; (b) Gamo, F. J.; Sanz, L. M.; Garcia-Bustos, J. F. Nature 2010, 465, 305.
3
4, 673.
1. (a) Romanov-Michailidis, F.; Pupier, M.; Alexakis, A. Chem. Commun. 2014,
3461; (b) Ye, W.-M.; Li, W.-B.; Zhang, J.-L. Chem. Commun. 2014, 9879; (c)
4
5
.
.
Hu, Y.-G.; Zheng, A.-H.; Li, W. J. Heterocycl. Chem. 2014, 51, E84.
(a) Kanawade, S. B.; Patil, S. P.; Toche, R. B. J. Heterocycl. Chem. 2012, 49, 363; (b)
Bondock, S.; Tarhoni, A. E.-G.; Fadda, A. A. Phosphorus, Sulfur Silicon Relat. Elem.
2
1
Song, Z.-L.; Fan, C.-A.; Tu, Y.-Q. Chem. Rev. 2011, 111, 7523.
2. Yang, J.-J.; Li, J.-R.; Shi, D.-X. Dyes Pigments 2015, 116, 97.
3. Kikaš, I.; Horváth, O.; Škori c´ , I. Tetrahedron Lett. 2011, 52, 6255.
2
007, 182, 1915.
2
2
6
.
(a) Pauwels, L.; Inzé, D.; Goossens, A. Trends Plant Sci. 2009, 14, 87; (b) Nicolaou,
K. C.; Nilewski, C.; Nagrath, D. J. Am. Chem. Soc. 2015, 137, 4766; (c) Carney, D.