Efficient synthesis and antioxidant activities of N-heterocyclyl substituted Coenzyme Q analogues

Article abstract of DOI:10.1016/j.bioorg.2016.08.008

A new strategy for the efficient synthesis of C-5 heterocyclyl substituted Coenzyme Q analogues was developed by N-alkylation of bromomethylated quinone 11 with a series of amines 12 under metal-free conditions. In vitro antioxidant activities of these Coenzyme Q analogues were evaluated and compared with commercial antioxidant Coenzyme Q₁₀ by employing DPPH assay. All these N-heterocyclyl substituted Coenzyme Q analogues are found to be exhibiting good antioxidant properties and may be used as potent antioxidants for combating oxidative stress.

Full text of DOI:10.1016/j.bioorg.2016.08.008

Accepted Manuscript
Efficient synthesis and antioxidant activities of N-heterocyclyl substituted
Coenzyme Q analogues
Jin Wang, Fei Xia, Wen-Bin Jin, Jin-Yan Guan, Hang Zhao
PII:
S0045-2068(16)30104-3
DOI:
http://dx.doi.org/10.1016/j.bioorg.2016.08.008
YBIOO 1942
Reference:
Bioorganic Chemistry
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Revised Date:
Accepted Date:
2 July 2016
7 August 2016
17 August 2016
Please cite this article as: J. Wang, F. Xia, W-B. Jin, J-Y. Guan, H. Zhao, Efficient synthesis and antioxidant activities
of N-heterocyclyl substituted Coenzyme Q analogues, Bioorganic Chemistry (2016), doi: http://dx.doi.org/10.1016/
j.bioorg.2016.08.008
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Efficient synthesis and antioxidant activities of N-heterocyclyl
substituted Coenzyme Q analogues
Jin Wanga*, Fei Xiaa, Wen-Bin Jina, Jin-Yan Guana, Hang Zhaoa
aSchool of Pharmacy, Yancheng Teachers University, Yancheng 224007, Jiangsu
Province , P. R. China
e-mail: woongching@hotmail.com or wangj01@yctu.edu.cn
ABSTRACT:
A new strategy for the efficient synthesis of C-5 heterocyclyl substituted Coenzyme Q
analogues was developed by N-alkylation of bromomethylated quinone 11 with a
series of amines 12 under metal-free conditions. In vitro antioxidant activities of these
Coenzyme Q analogues were evaluated and compared with commercial antioxidant
Coenzyme Q10 by employing DPPH assay. All these N-heterocyclyl substituted
Coenzyme Q analogues are found to be exhibiting good antioxidant properties and
may be used as potent antioxidants for combating oxidative stress .
Keywords: CoQ analogues N-alkylation DPPH assay antioxidant activities
1. Introduction
Oxidative stress plays critical roles in the pathogenic mechanisms of several
neurodegenerative disorders including Alzheimer’s disease, the increased levels of
free radicals and reactive oxygen species (ROS) would cause damage to cell
1

membrane, lipids, proteins and DNA.[1] Thus, much research effort has focused on
antioxidants as potential treatment agents for oxidative stress-related diseases.[2]
Coenzyme Qn (CoQ, or ubiquinone, Fig. 1) is a molecule with a side-chain of
different hydrophobic isoprenoid units, occur naturally in all cells, acting as electron
carriers in mitochondrial respiratory chain.[1,2] CoQ10 (n=10, Fig.1), the main
homologue of CoQ existing in humans, is our only lipid-soluble antioxidant
synthesized endogenously and efficiently prevents proteins, lipids and DNA from
oxidation of reactive oxygen species (ROS). CoQ10 and its analogue, is widely used in
the treatment of mitochondrial disorders and neurodegenerative movement disorders,
such as cardiovascular disease, Parkinson’s disease, Alzheimer’s disease, Friedreich’s
ataxia, etc.[3-5] CoQ10 is also used as a diet supplement in elderly people to maintain
health, and there is an increasing market demand.[6]
CoQ analogues with mimic of alkyl chain by other functional groups have been
widely reported and also studied with biological activity, [7-13]such as inhibition of
mitochondrial complex I and blood platelet aggregation, as novel inhibitors of
glycation and anticancer agents, as drugs for the treatment of Alzheimer's and
Parkinson’s diseases, etc. But there were no antioxidant activity data reported for all
these CoQ analogues. In 1989, Yoshizawa reported that some heterocyclyl-substituted
CoQ derivatives could be used as drugs, such as compound I (Fig.1) which showed
good inhibition of blood platelet aggregation and peroxy lipids in rat brain [13]. To the
best of our knowledge, there are few methods disclosed for the preparation of these
N-heterocyclyl substituted CoQ analogues, among the reported approaches, some
2

used dangerous or toxic reagent (n-BuLi, Ag2O, AgNO3, Pd(PPh3)4, etc), harsh
reaction conditions, or multiple steps.[9-11,13] These drawbacks limited their wide
application in industry and academia. Therefore, development of an efficient and
environmentally friendly methods to synthesis of substituted CoQ analogues bearing a
N-heterocyclic
unit
is
desirable.
Inspired
by
the
reports
that
halogenmethyl-1,4-benzoquione had reactivity in an electron-transfer C-alkylation
reaction,[14-16] herein, we reported a direct approach to N-heterocyclyl substituted CoQ
analogues by N-alkylation of bromomethylated quinone 11 with various
N-heterocyclic compounds via SN2 reaction, and we also investigated the antioxidant
activities of these synthesized CoQ analogues by DPPH assay in vitro.
Figure 1. Coenzyme Qn and Compound I
2. Results and Discussion
2.1 Chemistry
In our previously work,[17] we described an efficient approach for the preparation of
2,3,4,5-Tetramethoxytoluene 4. Initially, treatment of commercially available
3,4,5-trimethoxybenzadehyde 1 under Wolff–Kishner conditions provided 2 in
quantitative yield, then bromination of 2 utilizing NaBr–H2O2 system gave bromide 3
3

in 98% yield, finally, SNAr reaction of 3 with CH3ONa–CH3OH under cuprous salts
catalyst to afford 4 in overall 91 % yield (based on 1). In view of the difficulties
associated with the preparation of previous CoQ analogues, the availability of
compound 4 prompted us to devise a practical route to compound I, an
N-heterocyclyl substituted CoQ analogue which could be developed to drug.
.
Scheme 1. Reagents and conditions: (a) 80% NH2NH2 H2O, ethylene glycol,
KOH,70℃/2 h, 150℃/2 h, 100 %; (b) NaBr, 30% H2O2, HOAc, 40℃, 1h, 98 %; (c)
CH3ONa, CH3OH, CuCl, DMF, 100℃, 4h, 93 %
In order to synthesize compound I, a regioselective protected piperirazine would to
be synthesized as the secondary amine for the optimization of the alkylation reaction.
So we have to synthesize N-Benzylpiperazine first. There have been few reports of
the direct transformation of piperazine to mono benzyl piperazine, most of them
employ the direct benzylation of piperazine or start from mono-protected N-acyl- and
N-aroylpiperazines under very cautious control of the pH of the reaction mixture,
however, these methods always produce a mixture of dibenzylpiperazine from which
N-benzylpiperazine 8a is difficult to isolate.[18] Inspired by literature,[19]
N-benzylpiperazine 8a was achieved in 95 % yield without the need of using a
monoprotected piperazine. Firstly, converting anhydrous piperazine 5 to its somewhat
4

intermediate monohydrochloride 7 in situ by reaction with piperazine dihydrochloride
6 in ethanol at reflux for 2 h, following reacted with benzyl chloride at the same
temperature, as shown in Scheme 2. Using the similar way, we also got
N-benzoylpiperazine 8b in 94 % yield.
Scheme 2. Reagents and conditions: (a) ethanol, 75℃, 2h; (b) benzyl chloride or
benzoyl chloride, 75℃, 2h
Inspired by our previous work,[17e,f] we use 47 % HBr solution as Blanc Reaction
reagent instead of 37% HCl. Benzylbromide 9 was obtained in 98 % yield by
bromomethylation of 4 using paraformaldehyde and 47 % HBr solution under
solvent-free conditions. We envision that compound I could be synthesized by
oxidation of compound 10, as anticipated, compound 10 was obtained in 89 % yield
by amination of 9 and 8a in the presence of K2CO3 in DMF at 80 ℃ for 2 h.
Unfortunately, the final oxidation to compound I, using ceric ammonium nitrate
(CAN), gave only a trace amount of the ubiquione I and we could not improve this
yield. We speculated that the piperazine group in compound 10 might also be oxidized
by CAN during the reaction, the lack of success with this step forced us to
consideration of avoiding the final oxidation altogether by using bromomethylated
quinone 11 directly, instead of benzylic bromide 9 (Scheme 3). Then we tried another
5

route: Firstly, oxidation of benzylic bromide 9 with CAN successfully afforded the
desired bromomethylated quinone 11,[20] following by N-alkylation of 11 (1 equiv.)
with 8a (1.1 equiv.) in the presence of K2CO3 (1.2 equiv.) in dichloromethane (DCM)
at 25 ℃, we were delighted to know that our desired was indeed formed in 58 %
yield (Table 1, entry 1).
Scheme 3. Reagents and conditions: (a) (HCHO)n, 47 % HBr, 40℃, 1h, 98 %; (b)
K2CO3, DMF, 80 ℃, 2h, 89 %; (c) Ceric ammonium nitrate (CAN), THF/H2O, 0 ℃，
80%; (d) K2CO3, DCM, 25 ℃, 58 %
The N-alkylation of bromomethylated quinone 11 was investigated under different
conditions, the results are summarized in Table 1. The yield of compound I was
decreased from 58 % to 35 % when 10% NaOH solution was instead with K2CO3
(Table 1, entry 2), when we added 10% NaOH solution to the reaction, we found that
the color of reaction mixture changed to abnormal purple which indicated the
bromomethylated quinone 11 was destroyed by the strong base. Different solvents
6

(THF, DMF, EtOH) were also investigated, the reaction only proceed at higher
temperature (60-80 ℃, Table 1, entries 5,7,9) not at 25 ℃ (Table 1, entries 4,6,8).
However, lower yields were obtained in all cases (Table 1, entries 5,7,9), indicating
that DCM is the suitable solvent and K2CO3 is a good base for this reaction. On basis
of these screening studies, the optimal condition was using 11 (1 equiv.), 8a (1.1
equiv.) and K2CO3 (1.2 equiv.) in dichloromethane (DCM) at 40 ℃ for 0.5 h.
Table 1. Table optimization of N-alkylation conditions a
Entry
solvent
DCM
DCM
DCM
THF
base
K2CO3
10% NaOH
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Time (h)
Yield b (%)
Temp (℃ )
1
2
3
4
5
6
7
8
9
6
6
25
25
40
25
60
25
80
25
70
58
35
75
0
0.5
6
THF
2
60
0
DMF
DMF
EtOH
EtOH
6
2
55
0
6
2
62
a reaction conditions: 11 (1mmol), 8a (1.1 equiv), base (1.2 equiv), and solvent (5 ml)
b isolated yields
7

With the optimized conditions, various commercially available amines 12 were
investigated in the N-alkylation and the results were summarized in Table 2. The
N-alkylation proceeded smoothly in the presence of K2CO3 in DCM at 40 ℃,
commercially available amines (morpholine 12a, piperidine 12b) and
N-benzoylpiperazine 8b all underwent efficient amination (Table 2, entries 1-4).
Compared with our early study,[17f] it’s interesting to note that utilizing the -CH2Br
synthetic intermediate (11), rather than -CH2Cl, good yields of target compounds were
obtained in the N-alkylation reaction.
Table 2. N-alkylation of bromomethylated quinone 11 with different amines a
entry
R
Yieldb
(%)
70
amines 12
CoQ 13
1
2
3
12a
12b
8b
13a
13b
13c
60
80
a reaction conditions: 11 (10 mmol), 8a (1.1 equiv), K2CO3 (1.2 equiv), and DCM (10
ml), 40 ℃, 0.5 h. b isolated yields
2.2 DPPH free radical antioxidant activity
DPPH radical scavenging activity evaluation is a rapid and convenient technique
8

for screening the antioxidant activities of the antioxidants.[26] The antioxidant
activity was defined as the amount of CoQ analogues necessary to decrease the initial
DPPH concentration by 50% and expressed as IC50. The results of CoQ analogues
(CoQ0, I, 13c, 13a, 13b, CoQ10) were shown in Table 3. Based on IC50 values, their
DPPH radical-scavenging activity follows the order: 13c > I > CoQ10 > 13a > 13b >
CoQ0. Among the compounds tested, all the compounds (I, 13c, 13a, 13b) showed
better radical scavenging activities than Coenzyme Q0, with IC50 values of 0.609,
0.294, 2.638, 3.471 mM, respectively. In addition, compound I and 13c displayed
better DPPH radical scavenging activity than Coenzyme Q10, with IC50 values of 1.212
mM. On the basis of the above observation, the introduce of heterocyclic substituent
at the C-5 position of Coenzyme Q might increase its antioxidant activity.
Table 3. Antioxidant activities of N-heterocyclyl substituted CoQ analogues
compounds R
IC50(mM) SD(mM)
CoQ0
I
H
3.664
0.609
0.294
2.638
3.471
1.212
0.025
0.032
0.041
0.027
0.039
0.058
13c
13a
13b
CoQ10
[a] SD, standard deviation of three experiments.
9

3. Conclusions
In summary, we have developed a simple, mild, efficient, and eco-friendly method
for the synthesis of C-5 N-heterocyclyl substituted CoQ analogues. Moreover, we
demonstrated an easy and efficient way of direct transformation of free piperazine to
mono benzyl or benzoyl piperazine under metal-free conditons. All these reactions are
operationally simple, environmentally friendly, easy to work-up, high yields and take
place under mild conditions. Therefore, this strategy would have potential industrial
application in the preparation of a wide variety of biologically active Coenzyme Q
analogues.
What’s more, all the N-heterocyclyl substituted Coenzyme Q analogues were
evaluated for the DPPH radical antioxidant activity, experimental results
demonstrated that all the synthesized CoQ analogues showed good antioxidant
properties. Especially, compounds I and 13c bearing a piperazine group showed better
radical scavenging activities than Coenzyme Q10 in DPPH assay, which means
compounds I and 13c may displayed more potential antioxidant activities than
Coenzyme Q10 and may be developed as the potential therapeutic antioxidants for
oxidative stress-related diseases.
4. Experimental Section
General methods: The synthesised CoQ analogues were purified by silica gel (80–120
mesh) column chromatography (Adamas-beta, China) and identified by thin-layer
1
chromatography (TLC), MS, and NMR analysis. H NMR spectra and 13C NMR were
10

recorded on a Bruker DRX NMR spectrometer and a API STAR Pulsar mass
spectrometer, respectively. A UV-2550 UV–Vis spectrophotometer from Shimadzu
was used in the scavenging assays. 2,2-Diphenyl-1-picrylhydrazyl free radical
(DPPH), Coenzyme Q10, Coenzyme Q0, Ceric ammonium nitrate (CAN), piperazine,
piperidine and morpholine were purchased from Adamas-beta, China. Other
chemicals used were of analytical grade.
4.1 Synthesis
General procedure for the synthesis of compounds (8a ,8b).
A solution of anhydrous piperazine (5, 8.6 g, 0.1 mol) and piperazine dihydrochloride
(6, 31.8g 0.2mol) in ethanol (80 mL) were heated with vigorous stirring at 75 °C for 2
h. Then a solution benzyl chloride (13.9g, 0.11mol) or benzoyl chloride (15.4g,
0.11mol) was added dropwise over a period of 40 minutes to the hot solution. The
reaction mixture was refluxed for another 2 h, the progress of the reaction was
monitored by TLC. The mixture was cooled and the precipitated piperazine
dihydrochloride 6 was collected and washed three times with ethanol. The filtrate
combined with the washes was concentrated in vacuo to give the N-benzylpiperazine
or N-benzoylpiperazine hydrochloride which was then treated with 6M NaOH to
pH >12. The aqueous layer of crude N-benzylpiperazine or N-benzoylpiperazine was
extracted into CH2Cl2 (3 × 50 mL). The combined organic extracts were dried over
Na2SO4 and concentrated in vacuo. The crude oily product was purified by flash
column chromatography on silica gel (MeOH-CH2Cl2 1:3) to give 8a (18.4 g, 95%) or
11

8b (17.8 g, 94 %).
Data for 8a:[21] 1H NMR (500MHz, CDCl3
7.34-7.28 (m, 5H, Ph), 3.57 (s, 2H,
OBn), 3.23 (s, 4H, piperazine-H), 2.77 (s, 4H, piperazine-H). MS (ESI): m/z =177
[M+H] +. Spectroscopic data are according to the literature. [21]
Data for 8b:[22] 1H NMR(500MHz, CDCl3): 7.40 (s, 5H, Ph-H), 3.78 (s, 2H), 3.42 (s,
2H), 2.40-3.10 (m, 5H). MS (ESI): m/z =191 [M+H]+. Spectroscopic data are
according to the literature. [22]
Synthesis of compound 9 [23]
To a stirred mixture of 4 (2.12 g, 0.01mol) and paraformaldehyde (0.60 g, 0.02mol)
was added 47% HBr (10ml) dropwise at room temperature. Then the mixture was
stirred at 40℃ for 1 h, Water were added and the mixture was extracted with
petroleum ether, and the combined organic layers were washed with brine. The
solution are dried over anhydrous sodium sulfate and solvent was removed in vacuo
to afford an orange oil 9 (2.98 g, 98% yield). 1H NMR (400MHz, CDCl3): 4.68 (s, 2H,
CH2Br), 3.93 (s, 3H, OCH3), 3.92 (s, 3H, OCH3), 3.89 (s, 3H, OCH3), 3.78 (s, 3H,
OCH3), 2.28 (s, 3H, CH3). Spectroscopic data are according to the literature. [23]
Synthesis of compound 10
Compounds 9 (1.15 g, 3.8 mmol), N-benzoylpiperazine 8a (0.67 g, 3.8 mmol) , and
K2CO3 (0.63 g, 4.56 mmol) in DMF (10 ml) were heated at 80 ℃ for 2 h, After
completion of the reaction, the crude was extracted with three portions of CH2Cl2.
12

The yellow extracts were washed with brine until neutrality, then dried over
anhydrous Na2SO4 and concentrated in vacuo. The crude oily product was purified by
a silica-gel column chromatography (PE/EtOAc 3:1) to give a yellow oil 10 (3.7 g,
89%).
1H NMR (300MHz, CDCl3):7.30-7.29 (m, 5H, Ph), 3.91 (s, 3H, OCH3), 3.87 (s, 3H,
OCH3), 3.81 (s, 3H, OCH3), 3.77 (s, 3H, OCH3), 3.49 (s, 2H, CH2), 3.46 (s, 2H, CH2),
2.49(brs, 8H, piperazine), 2.24 (s, 3H, CH3); 13C NMR(75MHz, MeOD): 148.9, 147.7,
146.0, 144.3, 138.1, 129.3(2C), 128.2(2C), 127.4, 127.0, 125.4, 63.1, 61.2, 61.0, 60.6,
53.3, 52.8, 11.8; MS(ESI): m/z = 401 [M+H] +. Calcd for C H27 O4N2: 401.2440.
21
Found: 401.2433.
Synthesis of compound 11 [24]
A solution of CAN (21.9 g, 0.04 mol) in water (15 mL) was added dropwise to a
solution of compound 9 (3.04 g, 0.01 mol) in THF (10 mL) at 0 ℃. The mixture was
stirred at room temperature for another 2 h. The progress of the reaction was
monitored by TLC. After completion of the reaction, the crude was extracted with
three portions of CH2Cl2 (15 mL). The orange extracts were washed with brine until
neutrality, then dried over anhydrous Na2SO4 and concentrated in vacuo. The crude
product were purified by a silica-gel column chromatography (PE/EtOAc 4:1) to give
an orange oil 11 (2.2 g, 80 % yield).
1H NMR (500MHz, C5D5N-d5): 4.29 (s，2H, CH2Br), 3.88 (s, 3H, OCH3), 3.86 (s, 3H,
OCH3), 1.99 (s, 3H, CH3); 13C NMR (125 MHz, MeOD): 183.7 (C=O), 181.6 (C=O),
13

144.7, 144.2, 142.3, 136.7, 61.2 (OCH3), 61.1 (OCH3), 35.0 (CH2Br), 11.8 (CH3).
Spectroscopic data are according to the literature. [24]
General procedure for the synthesis of compound I and 13
A mixture of compounds 11 (2.74 g, 10 mmol), amine 12 (11 mmol), and K2CO3 (1.66
g, 12 mmol) in CH2Cl2 (10 ml) were heated at 40 ℃ for 0.5 h. The progress of the
reaction was monitored by TLC, after completion of the reaction, the reaction mixture
was extracted with three portions of CH2Cl2. The orange extracts were washed with
brine until neutrality, then dried over anhydrous Na2SO4 and concentrated in vacuo.
Then the residue was were purified by a silica-gel column chromatography
(PE/EtOAc 3:1) to give the desired compounds.
1
Data for compound I : HNMR (500MHz, MeOD): 7.60-7.58 (m, 2H, Ph), 7.52-7.50
(m,3H, Ph), 4.46 (s, 2H, CH2), 4.20 (s, 2H, CH2), 4.01 (s, 3H, OCH3), 4.00(s, 3H,
OCH3), 3.58(brs, 8H, Piperazine-CH2), 2.20 (s, 3H, CH3).
+
HRMS(ESI): m/z = 371 [M+H] . Calcd for C 21H27 O4N2: 371.1970. Found:
371.1969.
1
Data for 13c : H NMR (500MHz, C5D5N-d5): 7.35–7.33 (m, 5H, Ph), 3.95 (s, 3H,
OCH3), 3.94 (s, 3H, OCH3), 3.69 (brs, 2H, CH2N), 3.37 (s, 2H, CH2), 3.32 (brs, 2H,
CH2N), 2.49 (brs, 2H, CH2N), 2.33 (brs, 2H, CH2N), 2.07 (s, 3H, CH3).
13C NMR (125 MHz, MeOD): 184.4 (C=O), 183.8 (C=O), 170.2 (C=O), 144.3,
142.9, 137.3, 135.6, 129.6, 128.4, 126.9, 61.2 (2×OCH3), 53.4 (CH2N), 52.9 (CH2N),
51.5 (CH2), 47.6 (CH2N), 42.0 (CH2N), 12.4 (CH3).
MS(ESI): m/z = 383 [M-H]-
14

Data for 13a:[10] 1HNMR (500MHz, CDCl3): 3.96 (s, 3H, OCH3), 3.94 (s, 3H, OCH3),
3.65 (t, J = 4.3 Hz, 4H), 3.38 (s, 2H, CH2), 2.43 (t, J = 4.3 Hz, 4H), 2.16 (s, 3H, CH3).
Spectroscopic data are according to the literature. [10]
Data for 13b:[25] 1HNMR (400MHz, CDCl3): 4.01 (s, 3H, OCH3), 3.99 (s, 3H, OCH3),
3.32 (s, 2H, CH2), 2.36 (brs, 4H), 2.12 (s, 3H, CH3), 1.53 (brs, 4H), 1.37-1.42 (m, 2H).
Spectroscopic data are according to the literature. [25]
4.2. DPPH free radical antioxidant activity
In vitro antioxidant activities were measured against 2,2-diphenyl-1-picrylhydrazyl
(DPPH).[26] The values of IC50, the effective concentration at which 50% of radicals
were scavenged, were tested to evaluate the antioxidant activities. Generally, a lower
IC50 values indicated higher antioxidant activity, the IC50 of commercial Coenzyme Q0
and Coenzyme Q10 were measured for comparison. Each sample solution (4 mL) in
anhydrous ethanol at different concentrations (0.05，0.1，0.2，0.4 and 0.8mg/ml) was
added to the solution (4 mL, 0.05 mg/ml) of DPPH in anhydrous ethanol. The reaction
mixture was incubated at 30 ℃. The scavenging activity on DPPH free radical was
determined by measuring the absorbance at 517 nm after 30 min. The scavenging
activity was expressed as a percentage of scavenging activity on DPPH:
scavenging activity (%) = [(Acontrol –Atest) /Acontrol)] × 100
where Acontrol is the absorbance of the control (DPPH solution without test sample)
15

and Atest is the absorbance of the test sample (DPPH solution plus scavenger). The
control contains all reagents except the scavenger. The DPPH radical scavenging
activity of Coenzyme Q0 and Coenzyme Q10 were also assayed for comparison, all
tests were performed in triplicate. Percent inhibition after 30 min was plotted against
concentration, and the equation for the line was used to obtain the IC50 value, the data
caculated for antioxidantion are presented as means + SD of three experiments.
Acknowledgments
This study was supported by the National Natural Science Foundation for Young
Scientists of China, the Natural Science Foundation of Jiangsu Province
(BK20160443), the College students practice innovation training program of
Yancheng Teachers University, the Natural Science Foundation of Yancheng Teachers
University.
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Graphical abstract
Efficient Synthesis and antioxidant activities of N-heterocyclyl substituted Coenzyme Q
analogues
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Highlights
1. A new strategy for the efficient synthesis of C-5 heterocyclyl substituted
Coenzyme Q analogues was developed.
2. All the N-heterocyclyl substituted Coenzyme Q analogues are exhibiting good
antioxidant properties.
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