Base-Free Synthesis and Synthetic Applications of Novel 3-(Organochalcogenyl)prop-2-yn-1-yl Esters: Promising Anticancer Agents

Article abstract of DOI:10.1055/a-1477-6470

This manuscript portrays the CuI-catalyzed Csp-chalcogen bond formation through cross-coupling reactions of propynyl esters and diorganyl dichalcogenides by using DMSO as solvent, at room temperature, under base-free and open-to-air atmosphere conditions.

Full text of DOI:10.1055/a-1477-6470

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, A–M
paper
A
en
F. Gritzenco et al.
Paper
Synthesis
Base-Free Synthesis and Synthetic Applications of Novel 3-(Organo-
chalcogenyl)prop-2-yn-1-yl Esters: Promising Anticancer Agents
Fabiane Gritzencoa
Jean C. Kazmierczakb
Thiago Anjosb
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3
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4
2
3
9
-6
8
2
7
glioblastoma
cells
Adriane Sperançac
Maura L. B. Peixotod
Marcelo Godoid
anticancer
assay
Kauane N. B. Ledebuhre
César Augusto Brüninge
Lauren L. Zamina
O
O
(R2Y)2 (0.6 equiv)
R1
R1
O
O
CuI (10 mol%)
DMSO (2 mL)
r.t., air
YR2
Z
Z
Benhur Godoi*a
0
0
0
0
-
0
0
0
1
-
7
4
3
7
-
9
6
5
6
Y = Se, Te; Z = C, N
cross-
coupling
a Programa de Pós-Graduação em Ambiente e Tecnologias Sustentáveis, Núcleo
de Síntese, Aplicação e Análise de Compostos Orgânicos e Inorgânicos, Federal
University of Fronteira Sul, Cerro Largo 97900-000, RS, Brazil
benhur.godoi@uffs.edu.br
b Departamento de Química, Universidade Federal de Santa Maria-UFSM,
97105-900 Santa Maria, RS, Brazil
Csp–Csp2
and
Csp–Csp
formation
jeanckazmierczak@gmail.com
c Instituto Federal Farroupilha, Santo Ângelo, RS, Brazil
adriane.speranca@iffarroupilha.edu.br
d Escola de Química e Alimentos, Universidade Federal do Rio Grande, Campus
Santo Antônio da Patrulha, RS, Brazil
marcelogodoi@furg.br
e Laboratório de Bioquímica e Neurofarmacologia Molecular, Programa de
Pós-Graduação em Bioquímica e Bioprospecção, Centro de Ciências Químicas,
Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, RS,
Brazil
cabruning@yahoo.com.br
Corresponding Author
Received: 06.03.2021
Accepted after revision: 08.04.2021
Published online: 08.04.2021
areas such as organic synthesis,2 pharmacology,3 and mate-
rial science.4 Both, natural and synthetic benzoate deriva-
tives are known to compose the molecular scaffold of or-
ganic substances, which present biological and pharmaco-
logical properties as antimicrobial,5 pesticide,6 anti-
inflammatory,7 anesthetic,8 and anticancer9 activities.
On the other hand, organochalcogen-derived com-
pounds are known to present relevant biological and phar-
macological activities.10 Indeed, organoselenium and or-
ganotellurium derivatives have become attractive synthetic
targets particularly due their applications on the pharma-
cological field. Among their broad range of properties are
included antioxidant,11 antimicrobial,12 anti-inflammato-
ry,13 antidepressive-like,14 and anticancer15 activities. In
fact, selenium is considered an essential micronutrient for
the mammalian diet being a structural component of en-
zymes and crucial to several metabolic pathways.16 Besides,
the introduction of an organochalcogen group into the
structure of organic molecules consists in a very interesting
and versatile synthetic tool, since the carbon–chalcogen
bond might be easily replaced for new carbon–carbon bond
through different synthetic transformations such as chalco-
gen/lithium exchange and transition-metal-catalyzed
cross-coupling reactions.17
DOI: 10.1055/a-1477-6470; Art ID: ss-2021-m0111-op
Abstract This manuscript portrays the CuI-catalyzed Csp-chalcogen
bond formation through cross-coupling reactions of propynyl esters
and diorganyl dichalcogenides by using DMSO as solvent, at room tem-
perature, under base-free and open-to-air atmosphere conditions. Gen-
erally, the reactions have proceeded very smoothly, being tolerant to a
range of substituents present in both substrates, affording the novel 3-
(organochalcogenyl)prop-2-yn-1-yl esters in moderate to good yields.
Noteworthy, the 3-(butylselanyl)prop-2-yn-1-yl benzoate proved to be
useful as synthetic precursor in palladium-catalyzed Suzuki and
Sonogashira type cross-coupling reactions by replacing the carbon–
chalcogen bond by new carbon–carbon bond. Moreover, the 3-(phenyl-
selanyl)prop-2-yn-1-yl benzoate has shown promising in vitro activity
against glioblastoma cancer cells.
Key words organochalcogens, copper, catalysis, cross-coupling, glio-
blastoma
Esters are known as a very abundant class of natural
products, which are particularly responsible for the fruits
and flowers scents being largely applied into the industrial
and pharmacological fields.1 More specifically, benzoates
consist in a very important class of organic substances,
which has found a range of applications in several research
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–M
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
F. Gritzenco et al.
Paper
Synthesis
As a result of their pharmacological and synthetic appli-
cations, several studies have been focused on the develop-
ment and improvement of methodologies for the prepara-
tion of this class of substances.18 In this regard, transition-
metal-catalyzed cross-coupling and atom-economic addi-
tion reactions into alkynes and alkenes are well recognized
as the most important and efficient synthetic tools to pro-
mote the carbon–sulfur, carbon–selenium, and carbon–
tellurium bond formation.19 In the past years, indium, iron,
and silver salts have also been efficiently applied as cata-
lysts for the synthesis of chalcogenyl acetylenes.20 In partic-
ular, catalytic systems based on copper salts have emerged
as an alternative tool for the preparation of alkynyl chalco-
genides via Csp–H activation of terminal alkynes by avoid-
ing the use of strong bases or organometallic reagents, ally-
ing high efficiency with low cost and toxicity.21
Despite the number of studies related to the achieve-
ment of alkynyl chalcogenide derivatives, there is no report
regarding the synthesis of organochalcogen-containing
propynyl benzoates. Notably, the preparation of this kind of
compounds is very interesting since it allows exploring the
combination of well-known properties of benzoate deriva-
tives with that of the organochalcogens. According to the
above mentioned, herein we describe an atom-economic
approach for the synthesis of 3-(organochalcogenyl)prop-
2-yn-1-yl benzoates 3 through CuI-catalyzed cross-cou-
pling reactions of propynyl esters 1 and diorganyl dichalco-
genides 2, under mild and base-free reaction conditions
(Scheme 1). In addition to the synthetic studies, to our
knowledge, this is the first time that an alkynyl selenide
have demonstrated potential anticancer activity against a
GBM cell line.
the methodology, which is the atom-economic process
since both ‘PhSe’ moieties of diphenyl diselenide (2a) were
consumed during the formation of desired product. Next,
we evaluated the influence of the catalyst on the reaction
media (entries 4–10). By reducing the amount of the copper
salt from 10 to 5 mol% just a brief decrease in the reaction
yield was observed (entry 4). Similarly, a decrease in the re-
action yield was observed by increasing the amount of CuI
to 15 mol% (entry 5). Next, a screening of the copper salts
was realized, employing either copper(I) (CuCl, CuBr) or
copper(II) (CuBr2, CuO, CuOnano) species (entries 6–10).
However, no catalytic activity has been observed by using
these copper sources. In fact, the high catalytic activity of
the CuI for this transformation was confirmed once the de-
sired product was obtained in 88% yield by using only 10
mol% of this catalyst (entry 2). To verify the influence of the
reaction atmosphere we have carried out an experiment
under argon, which furnished the product 3a in lower yield
(entry 11). This result might indicate that the air plays an
important role for the catalytic system, most probably by
assisting the oxidative steps (see proposed mechanism).
The catalytic system showed to be highly dependent to
the use of DMSO as solvent since different protic and aprot-
ic solvents such as DCM, MeCN, EtOH, 1,4-dioxane, and THF
did not afford the desired product (Table 1, entries 12–16).
In this sense, a lower catalytic activity was observed when
DMF was employed as solvent leading to the product in 42%
yield (entry 17). The well-known coordinative and oxida-
tive properties of DMSO22 as well as the better solubility of
the catalyst might explain the higher efficiency of this sol-
vent when compared with others.
Regarding the reaction temperature, no improvement in
the yield value of 3a was observed by increasing the tem-
perature from 25 °C to 50 and 80 °C (Table 1, entries 18 and
19). Additionally, it was also observed that the presence of
base did not positively affect the catalytic efficiency of this
cross-coupling reaction (entries 20–22). By analyzing the
above results, we have established the ideal reaction condi-
tions as the use of CuI (10 mol%) as catalyst, diphenyl disel-
enide (2a) (0.6 equiv) as organochalcogen source, using
DMSO as solvent in the absence of base, under air at 25 °C.
Under these conditions the desired 3-(phenylselanyl)prop-
2-yn-1-yl benzoate (3a) was isolated in 88% yield after 24
hours (entry 2).
O
O
CuI
R2YYR2
+
R1
O
R1
O
DMSO, air
YR2
2
1
3
R1 = aryl, 3-pyridyl, styryl; R2 = aryl, alkyl; Y = Se, Te
Scheme 1 CuI-catalyzed cross-coupling reactions
In order to evaluate the most appropriate reaction con-
dition, the prop-2-yn-1-yl benzoate (1a) and diphenyl
diselenide (2a) were selected as standard substrates (Table
1). Several parameters were evaluated, which include stoi-
chiometry of substrates, base, solvent, amount and type of
the copper catalyst, temperature, and reaction atmosphere.
Initially, the desired 3-(phenylselanyl)prop-2-yn-1-yl ben-
zoate (3a) was obtained in 69% yield by treating 1a with 2a
(0.5 equiv) in DMSO as a solvent in the presence of CuI (10
mol%) under open-to-air atmosphere, at room temperature
(Table 1, entry 1). Nonetheless, by employing only a small
excess of 2a a significant improvement in the reaction yield
was achieved and the product 3a was synthesized in very
high yield (entry 2). Superior amount of diphenyl disele-
nide did not improve the reaction efficiency (entry 3).
These results have revealed an important characteristic of
To study the versatility and generality of the methodol-
ogy several experiments have been screened by using the
combination of different prop-2-yn-1-yl esters 1 and dior-
ganyl dichalcogenides 2 for the preparation of 3-(organose-
lanyl)prop-2-yn-1-yl esters 3 (Table 2). First, the substrate
1a was submitted to the reaction conditions in the presence
of different diorganyl diselenides 2 (Table 2, entries 1–11).
In terms of electronic effects, the methodology showed tol-
erance to the presence of electron-donating and -with-
drawing groups into the aromatic ring, affording the corre-
sponding products in good yields (entries 2–7). The reac-
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–M

C
F. Gritzenco et al.
Paper
Synthesis
tion seems to be slightly sensitive to steric effects in the
aromatic rings of diorganyl diselenides since the presence
of methyl groups at the ortho-position of the aromatic ring
lead to a decrease in the reaction yield (entries 8, 9). On the
other hand, when bis(1-naphthyl) diselenide (2j) was used
the corresponding product 3j was obtained in good yield
(entry 10). Furthermore, by employing the dibutyl disele-
nide (2k) as organochalcogen source it was possible to iso-
late the 3-(butylselanyl)prop-2-yn-1-yl benzoate (3k) bear-
ing an alkyl group directly bonded to the selenium atom
(entry 11).
with diphenyl diselenide (2a) under the same reaction con-
ditions (Table 2, entries 12–14). Generally, the reaction was
applicable for electron-donating and -withdrawing groups,
affording the corresponding products in reasonable yields
(entries 12–14). In particular, when a substrate bearing a
withdrawing fluorine atom was employed the correspond-
ing selenoacetylene 3n was achieved in 87% (entry 14). Ad-
ditionally, considering the well-known pharmacological
and biological potential of nicotinic and cinnamic acids de-
rivatives,23 prop-2-yn-1-yl nicotinate (1e) and prop-2-yn-
1-yl cinnamate (1f) were submitted to the cross-coupling
conditions by reacting with diphenyl diselenide (2a) and
the corresponding products 3o and 3p were efficiently ob-
tained in 60 and 92% yield, respectively (entries 15, 16).
Next, we evaluated the influence of substituents into
the aromatic ring of the prop-2-yn-1-yl benzoates 1 in the
cross-coupling reaction, by treating these terminal alkynes
Table 1 Determination of the Ideal Reaction Parameters for the Copper-Catalyzed Cross-Coupling of 1a and 2aa
O
O
copper catalyst, base
solvent, temperarure
O
O
PhSeSePh
+
SePh
1a
2a
3a
Entry
Catalyst (mol%)
PhSeSePh (equiv)
Base (equiv)
Solvent (2 mL)
Yield (%)b
1
2
CuI (10)
CuI (10)
CuI (10)
CuI (5)
0.5
0.6
0.75
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
–
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DCM
69
88
80
81
73
trace
trace
–
–
3
–
4
–
5
CuI (15)
CuBr (10)
CuCl (10)
CuBr2 (10)
CuO (10)
CuOnano (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
–
6
–
7
–
8
–
9
–
–
10
11
12
13
14
15
16
17
18
19
20
21
22
–
–
–
68c
–
–
–
MeCN
EtOH
trace
–
–
–
1,4-dioxane
THF
–
–
–
–
DMF
42
77d
73e
75
61
27
–
DMSO
DMSO
DMSO
DMSO
DMSO
–
K2CO3 (1.5)
NaHCO3 (1.5)
Et3N (1.5)
a The reaction was performed by using 1a (0.25 mmol), under air (open flask) at 25 °C for 24 h. The consumption of 1a was monitored by TLC.
b Yield for isolated products.
c The reaction was carried out under argon atmosphere.
d The reaction was carried out at 80 °C.
e The reaction was carried out at 50 °C.
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F. Gritzenco et al.
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Table 2 Synthesis of 3-(Organoselanyl)prop-2-yn-1-yl Esters 3a
O
O
R1
R1
CuI (10 mol%)
O
O
R2YYR2
+
YR2
Z
Z
DMSO (2 mL), 25 °C, air
1
3
2
Entry
1
Substrate 1
2 (R2Y)2
Product 3
Time (h)
24
Yield (%)b
88
O
O
O
O
O
O
2a (PhSe)2
Se
Se
Se
1a
1a
3a
3b
3c
3d
3e
3f
O
O
Me
2
3
4
5
6
7
8
2b (p-MeC6H4Se)2
2c (p-MeOC6H4Se)2
2d (m-MeOC6H4Se)2
2e (p-ClC6H4Se)2
2f (p-FC6H4Se)2
24
22
22
22
22
22
20
56
87
65
83
61
62
55
OMe
1a
1a
1a
1a
1a
1a
O
O
O
O
O
O
O
O
O
O
O
O
Se
Se
Se
Se
OMe
Cl
F
2g (m-CF3C6H4Se)2
2h (o-MeC6H4Se)2
CF3
3g
3h
Me
Se
Me
Me
9
1a
1a
2i (2,4,6-Me3C6H2Se)2
22
22
32
76
Se
Me
3i
O
10
2j (-C10H7Se)2
O
Se
3j
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–M

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F. Gritzenco et al.
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Synthesis
Table 2 (continued)
Entry
Substrate 1
2 (R2Y)2
Product 3
Time (h)
22
Yield (%)b
58
O
O
11
1a
2k (nC4H9Se)2
Se
3k
O
O
O
O
12
13
14
15
2a
2a
2a
2a
48
21
22
24
46
60
87
60
Se
Me
Me
1b
3l
O
O
O
O
OMe
Se
OMe
1c
3m
O
O
O
O
Se
F
F
1d
3n
O
O
O
O
Se
N
N
3o
1e
O
O
O
O
16
17
18
19
20
2a
24
24
24
24
24
92
64
40
0c
Se
1f
3p
3q
3r
3s
3t
O
O
1a
2l (PhTe)2
2m (nC4H9Te)2
2n (PhS)2
Te
O
O
O
O
O
O
1a
1a
1a
Te
S
Cl
2o (p-ClC6H4S)2
0c
S
a The reaction was carried out using the prop-2-yn-1-yl ester 1 (0.25 mmol), diorganyl diselenide 2 (0.6 equiv), CuI (10 mol%) in DMSO (2 mL), at 25 °C under air
(open flask). The consumption of 1 was monitored by TLC.
b Yield for isolated products.
c Only the starting materials were detected by GCMS analysis of the crude reaction mixture.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–M

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F. Gritzenco et al.
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Synthesis
In order to extend the scope to other organochalcogen
derivatives, the substrate 1a was reacted under the same
reaction conditions, in the presence of different diorganyl
ditellurides and disulfides (Table 2, entries 17–20). When
diphenyl and dibutyl ditellurides (2l and 2m) were em-
ployed as organochalcogen sources the expected 3-(phenyl-
tellanyl)prop-2-yn-1-yl benzoate (3q) and 3-(butyltel-
lanyl)prop-2-yn-1-yl benzoate (3r) were isolated in 60 and
40% yield, respectively (entries 17 and 18). The lower yield
observed in the presence of an alkyl group bonded to the
tellurium atom could be explained by the relatively lack of
stability of the product 3r. On the other hand, the reaction
system has failed to promote the cross-coupling reaction
using aromatic disulfides 2n and 2o since no products were
observed using the same reaction conditions (entries 19
and 20). This lack of reactivity of disulfides is most likely
explained due the higher strength of sulfur–sulfur bond
when compared with selenium analogues.24
The versatility and efficiency of the catalytic system has
been affirmed by submitting the di(prop-2-yn-1-yl) adipate
(1g) to the reaction conditions (Scheme 2). Particularly, this
double catalyzed cross-coupling process was conducted by
employing 1.2 equivalents of diphenyl diselenide (2a) and
10 mol% of the copper iodide leading to the desired bis[3-
(phenylselanyl)prop-2-yn-1-yl] adipate (3u) in 46% yield,
after 48 hours.
To secure more information about the mechanism some
control experiments have been accomplished (Scheme 3).
First, when the reaction was carried out in the absence of
CuI, no product formation was observed and the starting
materials 1a and 2a were totally recovered (Scheme 3, eq.
1). To check whether the cross-coupling reaction could in-
volve copper acetylide species,25 a Glaser-type reaction was
performed. Thus, when the substrate 1a was submitted to
standard conditions, in the absence of any diorganyl dichal-
cogenide, the formation of the homo-coupling product 1aa
was observed in only 12% yield even after 24 hours of reac-
tion time (Scheme 3, eq. 2). To evaluate the possibility of a
nucleophilic attack of the copper acetylide intermediate to
the diorganyl diselenide, compound 1a was stirred in the
presence of CuI (10 mol%) in DMSO for 2 hours followed by
the subsequent diphenyl diselenide (2a) addition, then the
reaction mixture was stirred for an additional 22 hours
(Scheme 3, eq. 3). In this case, only the cross-coupling prod-
uct 3a was obtained in 76% yield and not even traces of the
homo-coupling product 1aa was detected. Moreover, by an-
alyzing these results and considering that no homo-cou-
pling were detected during the scope development, the in
situ formation of a copper acetylide seems to be unlikely for
this synthetic transformation.
Considering the results achieved in the control experi-
ments and based on previous reports26 a plausible reaction
mechanism is shown in Scheme 4. First, a Cu(III)-complex A
O
O
O
O
CuI (10 mol%)
O
O
O
O
4
4
+ PhSeSePh
(1.2 equiv)
PhSe
SePh
DMSO (4 mL), 25 °C, air
48 h
1g
3u (46%)
2a
Scheme 2 CuI-catalyzed double cross-coupling reaction of 1g and 2a
O
O
O
O
CuI (10 mol%)
O
O
O
O
4
4
+ PhSeSePh
(1.2 equiv)
PhSe
SePh
DMSO (4 mL), 25 °C, air
48 h
1g
3u (46%)
2a
O
PhSeSePh (0.6 equiv)
DMSO (2 mL), 25 °C, air
24 h
O
(1)
SePh
3a (not observed)
O
O
O
CuI (10 mol%)
DMSO (2 mL), 25 °C, air
24 h
O
(2)
(3)
2
1a
1aa (12%)
O
1. CuI (10 mol%)
O
DMSO (2 mL), 25 °C, air, 2 h
2. PhSeSePh (0.6 equiv), 22 h
1aa
(not observed)
+
SePh
3a (76%)
Scheme 3 Mechanistic control experiments
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–M

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F. Gritzenco et al.
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Synthesis
could be formed through the interaction of the diorganyl
dichalcogenide 2 and CuI. Next, this complex would react
with the alkyne 1 to generate the intermediate B with con-
comitant formation of the organochalcogenol specie
(R2YH), which is immediately converted into the corre-
sponding diorganyl dichalcogenide 2 via an oxidative step.
Subsequently, the intermediate B might lead to the expect-
ed product 3 through reductive elimination process replac-
ing the copper(I) specie to the catalytic cycle. The in situ
formation of diorganyl dichalcogenides from oxidation of
chalcogenol species (R2YH) seems to be a reasonable expla-
nation since the reaction media required only 0.6 equiva-
lent of diorganyl dichalcogenide.
ArB(OH)2 (2 equiv)
Pd(PPh3)4 (10 mol%)
CuOAc.H2O (1.2 equiv)
O
O
Ph
O
Ph
O
SenBu
Ar
DMF (3 mL), 80 °C, argon, 3 h
O
3k
4a–f
O
Ph
O
Ph
O
4a (52%)
4b (83%)
Cl
O
O
Ph
O
Ph
O
4c (87%)
4d (46%)
Me
O
OMe
R2Y
R2Y
I
YR2
YR2
III
Cu
III
Cu
R1
O
O
O
I
A
1
OMe
Ph
O
Ph
O
4e (52%)
4f (58%)
(R2Y)2
2
R2YH
CuI
DMSO, air
Scheme 5 Suzuki type cross-coupling reactions of 3k and different
arylboronic acids
O
O
R1
O
YR2
III
Cu
R1
O
mas are classified as ependymomas, astrocytomas [includ-
ing glioblastoma (GBM)], oligodendrogliomas, mixed glio-
mas, and a few others.29 Despite the aggressive treatment
including surgical resection, chemotherapy with Temozolo-
mide (Tmz) and radiotherapy, median survival time for pa-
tients with GBM is only 14.6 months.30 GBM is an incurable
disease that almost invariably leads to neurological demise
and death. Due to its high degree of invasiveness, radical re-
section of the primary tumor mass is not curative. Infiltrat-
ing tumor cells invariably remain within the surrounding
brain, leading to disease progression or recurrence, either
locally or distant from the primary tumor.31 Therefore,
treatment of GBM remains one of the hardest challenges to
be tackled by oncotherapy.[32
In order to evaluate the anticancer activity of the syn-
thesized compounds, the 3-(phenylselanyl)prop-2-yn-1-yl
benzoate (3a) was chosen to initial studies due its great
synthetic availability in our research laboratory. Thus, the
treatment with 3a in the concentration of 10 M for 24
hours and the concentration of 50 and 100 M for 24, 48
and 72 hours significantly decreased the number of Human
GBM cell line A172 (Figure 1). The effects of 50 M (after 24
h of treatment) and 100 M (24 and 72 h) were similar to
that observed with the standard treatment used in the clin-
B
3
YR2
I
Scheme 4 Plausible reaction mechanism
The presence of carbon–chalcogen bond into an organic
structure allows the use of these substances as synthetic
precursors for the preparation of new target compounds
generally trough the replacement of the organochalcogen
moiety by other organic functions via transition-metal-cat-
alyzed transformations.27 In this way, the 3-(butyl-
selanyl)prop-2-yn-1-yl benzoate (3k) underwent palladi-
um-catalyzed Suzuki type cross-coupling reaction using
different arylboronic acids to form new carbon–carbon
bonds (Scheme 5). To our delight, the corresponding the
products 4a–f were efficiently achieved in moderate to ex-
cellent yields.
Aware of the synthetic importance of diynes as building
blocks to obtain several organic substances,28 the benzoate
3k was also submitted to palladium-catalyzed Sonogashira
type reaction with a tertiary propargylic alcohol, which
provided the expected unsymmetrical diyne 5a in 50% yield
(Scheme 6).
Glioma is a neuroepithelial tumor originating from the
glial or supporting cells of the central nervous system. Glio-
Pd(PPh3)2Cl2 (10 mol%)
CuOAc•H2O (20 mol%)
Et3N (4 equiv), DMF (3 mL)
O
O
OH
+
Ph
O
Ph
O
80 °C, 24 h
SenBu
(4 equiv)
OH
3k
5a (50%)
Scheme 6 Sonogashira type cross-coupling reaction of 3k and a tertiary propargylic alcohol
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–M

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F. Gritzenco et al.
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Synthesis
ic with Tmz. The greatest effect was observed after 24 hours
of treatment. This may have occurred due to the low insta-
bility of the compound 3a at 37 °C, which was experimen-
tally observed by GC-MS analysis, since the compound was
applied only once and left in contact with the cells for up to
72 hours.
very good yields. Besides, the synthetic potential of the car-
bon–chalcogen bond was also proved by employing the 3-
(butylselanyl)prop-2-yn-1-yl benzoate as a substrate in pal-
ladium-catalyzed Suzuki and Sonogashira type reactions,
which provided the generation of new carbon–carbon
bonds. In addition, we have demonstrated for the first time
the antitumor effect of the 3-(phenylselanyl)prop-2-yn-1-
yl benzoate (3a) in human glioma cell line, indicating a
promising molecule for the development of drugs that help
fight this disease.
1H NMR spectra were obtained at 400 MHz on a DPX-400 NMR spec-
trometer in CDCl3 solutions. Chemical shifts are reported in ppm, ref-
erenced to the solvent peak of CDCl3 or TMS as the external reference.
Data are reported as follows: chemical shift (), multiplicity, coupling
constant (J) in hertz and integrated intensity. 13C NMR spectra were
obtained at 100 MHz on a DPX-400 NMR spectrometer in CDCl3 solu-
tions. Chemical shifts are reported in ppm, referenced to the solvent
peak of CDCl3. Standard abbreviations were used to denote the multi-
plicity of a particular signal. Column chromatography was performed
using silica gel (230–400 mesh). TLC was performed using silica gel
GF254, 0.25 mm thickness. For visualization, TLC plates were either
placed under ultraviolet light, or stained with I2 vapor, or acidic vanil-
lin. Most reactions were monitored by TLC for disappearance of start-
ing material. Air- and moisture-sensitive reactions were conducted in
flame-dried or oven-dried glassware equipped with tightly fitted
rubber septa and under a positive atmosphere of dry argon. Reagents
and solvents were handled using standard syringe techniques.
Figure 1 3-(Phenylselanyl)prop-2-yn-1-yl benzoate (3a) induced cell
number decrease in GBM cell line A172. GBM cells were treated with 3a
at concentrations 1, 10, 50, and 100 M and Tmz at concentration 30
M for 24, 48 and 72 h. The upper line indicates the control cells treat-
ed with vehicle DMSO. Bars indicates mean ± SEM of at least three inde-
pendent experiments. * p <0.05; # p <0.01.
Some studies have demonstrated the antitumor effect of
organochalcogens33 in bladder carcinoma,34 cervical can-
cer,35 breast cancer,36 and chronic lymphocytic leukemia.37
Other studies have shown the effect of organoselenium,
such as diphenyl diselenide and selenadiazole in glio-
mas.38,39 However, to our knowledge, this is the first work
showing the antiglioma potential of an organochalcogen-
containing propynyl benzoates. The main mechanism by
which organochalcogen, mainly organoselenium com-
pounds, are considered promising antitumor agents is in
their broad antioxidant effect.33,34,36,40 The promising anti-
cancer activity exhibited by the benzoate 3a has encour-
aged our research group to proceed with the structure–
activity relationship studies of this class of organic substanc-
es, which are still under investigation in our laboratories.
In summary, we have described an efficient catalytic
system to promote the carbon–chalcogen bond formation
by reacting prop-2-yn-1-yl esters derivatives with differ-
ently substituted diorganyl diselenides and ditellurides, un-
der mild reaction conditions. The reactions were conducted
under ambient temperature and atmosphere (open flask)
under base-free conditions. The incorporation of both or-
ganochalcogen moieties from diorganyl dichalcogenides
into the target product structures gives an atom-economic
aspect to this synthetic methodology. Generally, the present
protocol have furnished a series of 3-(organochalcog-
enyl)prop-2-yn-1-yl esters bearing aromatic, aromatic sub-
stituted and alkyl groups bonded to the chalcogen atoms in
3-(Organochalcogenyl)prop-2-yn-1-yl)benzoates 3a–r and 3u;
General Procedure
In a reaction tube, under ambient atmosphere (air), containing the
appropriated diorganyl diselenide 2 (0.15 mmol, 0.60 equiv, for 3u 1.2
equiv) and CuI (10 mol%) at 25 °C was added DMSO (2 mL). To the
stirred reaction mixture was added the proper benzoate 1 (0.25
mmol) diluted in DMSO (1 mL), in one portion. The mixture was
stirred for the required time at 25 °C (Table 2). After that, the mixture
was quenched with sat. aq NH4Cl (5 mL) and the aqueous layer was
extracted with EtOAc (3 × 5 mL) and dried (MgSO4). After filtering, the
organic solution was concentrated using a rotary evaporator under
reduced pressure. The product was purified by flash chromatography
in silica gel using hexane/EtOAc as eluent.
3-(Phenylselanyl)prop-2-yn-1-yl Benzoate (3a)
Yield: 0.069 g (88%); yellow oil.
1H NMR (CDCl3, 400 MHz):  = 8.06–8.03 (m, 2 H), 7.53–7.48 (m, 3 H),
7.40–7.36 (m, 2 H), 7.29–7.19 (m, 3 H), 5.10 (s, 2 H).
13C NMR (CDCl3, 100 MHz):  = 165.5, 133.0, 129.6, 129.4, 129.2,
129.0, 128.2, 127.7, 127.1, 97.9, 68.1, 53.4.
MS (EI, 70 eV): m/z (%) = 316 (4), 211 (3), 193 (19), 159 (25), 115 (32),
105 (100), 77 (41), 51 (21).
HRMS: m/z calcd for C16H12O2Se [M + H]+: 317.0081; found: 317.0076.
3-(4-Tolylselanyl)prop-2-yn-1-yl Benzoate (3b)
Yield: 0.046 g (56%); yellow oil.
1H NMR (CDCl3, 400 MHz):  = 8.08–8.06 (m, 2 H), 7.58–7.54 (m, 1 H),
7.45–7.41 (m, 4 H), 7.13–7.11 (m, 2 H), 5.12 (s, 2 H), 2.32 (s, 3 H).
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–M

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F. Gritzenco et al.
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Synthesis
13C NMR (CDCl3, 100 MHz):  = 165.8, 137.5, 133.2, 130.3, 129.8,
129.7, 129.5, 128.3, 123.9, 97.2, 68.7, 53.6, 21.0.
1H NMR (CDCl3, 400 MHz):  = 8.09–8.08 (m, 1 H), 8.07–8.06 (m, 1 H),
7.79 (s, 1 H), 7.73–7.71 (m, 1 H), 7.58–7.54 (m, 1 H), 7.52–7.50 (m, 1
H), 7.46–7.43 (m, 2 H), 7.42–7.40 (m, 1 H), 5.14 (s, 2 H).
4
MS (EI, 70 eV): m/z (%) = 330 (6), 207 (14), 159 (23), 128 (44), 116 (8),
105 (100), 77 (32), 51 (11).
HRMS: m/z calcd for C17H14NO2Se [M + H]+: 331.0237; found:
331.0232.
13C NMR (CDCl3, 100 MHz):  = 165.8, 133.3, 132.3, 131.9 (q, JC,F
=
3
32.7 Hz), 129.8, 129.7, 129.5, 129.4, 128.4, 125.7 (q, JC,F = 4.1 Hz),
3′
124.1 (q
J
= 3.7 Hz), 123.5 (q, 1JC,F = 272.9 Hz), 99.4, 66.9, 53.4.
C,F
MS (EI, 70 eV): m/z (%) = 384 (2), 261 (12), 183 (14), 159 (17), 117 (7),
105 (100), 77 (33), 51 (13).
3-[(4-Methoxyphenyl)selanyl]prop-2-yn-1-yl Benzoate (3c)
HRMS: m/z calcd for C17H15NO2Se [M + H]+: 384.9954; found:
Yield: 0.067 g (87%); yellow oil.
384.9945.
1H NMR (CDCl3, 400 MHz):  = 8.07–8.04 (m, 2 H), 7.57–7.52 (m, 1 H),
7.50–7.46 (m, 2 H), 7.44–7.40 (m, 2 H), 6.87–6.83 (m, 2 H), 5.08 (s, 2
H), 3.76 (s, 3 H).
3-(2-Tolylselanyl)prop-2-yn-1-yl Benzoate (3h)
Yield: 0.045 g (55%); yellow oil.
13C NMR (CDCl3, 100 MHz):  = 165.7, 159.6, 135.3, 133.1, 132.2,
129.7, 128.3, 117.3, 115.3, 96.3, 69.4, 55.3, 53.5.
1H NMR (CDCl3, 400 MHz):  = 8.09–8.06 (m, 2 H), 7.76–7.54 (m, 1 H),
7.58–7.53 (m, 1 H), 7.45–7.41 (m, 2 H), 7.20–7.12 (m, 3 H), 5.14 (s, 2
H), 2.32 (s, 3 H).
13C NMR (CDCl3, 100 MHz):  = 165.8, 136.8, 133.2, 130.2, 129.8,
129.7, 129.5, 128.6, 128.4, 127.4, 127.2, 97.8, 68.0, 53.6, 20.9.
MS (EI, 70 eV): m/z (%) = 346 (8), 223 (7), 209 (7), 159 (10), 145 (19),
105 (100), 77 (29), 51 (8).
HRMS: m/z calcd for C17H14O3Se [M + H]+: 347.0186; found: 347.0182.
MS (EI, 70 eV): m/z (%) = 330 (3), 159 (6), 128 (73), 115 (11), 105
(100), 91 (9), 77 (24), 51 (8).
HRMS: m/z calcd for C17H14O2Se [M + H]+: 331.0237; found: 331.0232.
3-[(3-Methoxyphenyl)selanyl]prop-2-yn-1-yl Benzoate (3d)
Yield: 0.056 g (65%); yellow oil.
1H NMR (CDCl3, 400 MHz):  = 8.09–8.06 (m, 2 H), 7.60–7.54 (m, 1 H),
7.46–7.42 (m, 2 H), 7.25–7.19 (m, 1 H), 7.12–7.07 (m, 2 H), 6.81–6.78
(m, 1 H), 5.14 (s, 2 H), 3.81 (s, 3 H).
3-(Mesitylselanyl)prop-2-yn-1-yl Benzoate (3i)
Yield: 0.029 g (32%); yellow oil.
13C NMR (CDCl3, 100 MHz):  = 165.8, 160.3, 133.2, 130.2, 129.8,
129.5, 128.9, 128.4, 121.3, 114.5, 113.4, 98.4, 68.1, 55.3, 53.5.
1H NMR (CDCl3, 400 MHz):  = 8.06–8.05 (m, 1 H), 8.03–8.02 (m, 1 H),
7.58–7.54 (m, 1 H), 7.46–7.41 (m, 2 H), 6.95–6.94 (m, 2 H), 4.99 (s, 2
H), 2.56 (s, 6 H), 2.27 (s, 3 H).
13C NMR (CDCl3, 100 MHz):  = 165.8, 142.2, 139.4, 133.1, 129.8,
129.0, 128.4, 125.1, 92.1, 69.9, 53.7, 29.7, 24.1, 20.9.
MS (EI, 70 eV): m/z (%) = 346 (7), 223 (8), 75 (24), 145 (11), 115 (12),
105 (100), 77 (36), 51 (10).
HRMS: m/z calcd for C17H14O3Se [M + H]+: 347.0186; found: 347.0182.
MS (EI, 70 eV): m/z (%) = 358 (2), 236 (3), 141 (20), 119 (4), 105 (100),
91 (6), 77 (19), 51 (5).
HRMS: m/z calcd for C19H18O2Se [M + H]+: 359.0550; found: 359.0546.
3-[(4-Chlorophenyl)selanyl]prop-2-yn-1-yl Benzoate (3e)
Yield: 0.072 g (83%); yellow oil.
1H NMR (CDCl3, 400 MHz):  = 8.07–8.04 (m, 2 H), 7.57–7.53 (m, 1 H),
7.47–7.41 (m, 4 H), 7.29–7.25 (m, 2 H), 5.12 (s, 2 H).
13C NMR (CDCl3, 100 MHz):  = 165.8, 133.6, 133.2, 130.7, 129.8,
129.7, 129.6, 128.4, 126.2, 96.5, 67.7, 53.4.
3-(Naphthylselanyl)prop-2-yn-1-yl Benzoate (3j)
Yield: 0.069 g (76%); yellow oil.
1H NMR (CDCl3, 400 MHz):  = 8.07–8.05 (m, 2 H), 8.01–7.96 (m, 2 H),
7.85–7.83 (m, 1 H), 7.80 (d, J = 8.2 Hz, 1 H), 7.58–7.49 (m, 3 H), 7.45–
7.41 (m, 3 H), 5.12 (s, 2 H).
13C NMR (CDCl3, 100 MHz):  = 165.8, 134.1, 133.2, 132.2, 129.8,
129.6, 129.5, 128.7, 128.6, 128.4, 126.9, 126.4, 126.2, 125.5, 97.6, 68.1,
53.6, 29.7.
MS (EI, 70 eV): m/z (%) = 350 (3), 227 (10), 193 (8), 159 (18), 149 (17),
136 (7), 105 (100), 77 (36), 51 (15).
HRMS: m/z calcd for C16H11ClO2Se [M + H]+: 350.9691; found:
350.9684.
3-[(4-Fluorophenyl)selanyl]prop-2-yn-1-yl Benzoate (3f)
MS (EI, 70 eV): m/z (%) = 366 (6), 261 (4), 243 (20), 165 (18), 152 (9),
128 (9), 105 (100), 77 (24), 51 (5).
HRMS: m/z calcd for C20H14O2Se [M + H]+: 367.0237; found: 367.0233.
Yield: 0.051 g (61%); yellow oil.
1H NMR (CDCl3, 400 MHz):  = 8.09–8.06 (m, 2 H), 7.60–7.51 (m, 3 H),
7.47–7.43 (m, 2 H), 7.06–7.02 (m, 2 H), 5.12 (s, 2 H).
13C NMR (CDCl3, 100 MHz):  = 165.8, 162.5 (d, 1JC,F = 247.5 Hz), 133.3,
3-(Butylselanyl)prop-2-yn-1-yl Benzoate (3k)
3
4
131.8 (d, JC,F = 8.0 Hz), 129.8, 129.5, 128.4, 122.2 (d, JC,F = 3.3 Hz),
Yield: 0.043 g (58%); yellow oil.
116.8 (d, 2JC,F = 22.1 Hz), 97.7, 68.4, 53.5.
1H NMR (CDCl3, 400 MHz):  = 8.08–8.06 (m, 2 H), 7.59–7.54 (m, 1 H),
7.46–7.42 (m, 2 H), 5.01 (s, 2 H), 2.82 (t, J = 7.4 Hz, 2 H), 1.82 (quint, J =
7.3 Hz, 2 H), 1.44 (sext, J = 7.4 Hz, 2 H), 0.93 (t, J = 7.4 Hz, 3 H).
13C NMR (CDCl3, 100 MHz):  = 165.9, 133.1, 129.8, 129.7, 128.3, 94.2,
69.2, 53.7, 32.1, 29.0, 22.4, 13.4.
MS (EI, 70 eV): m/z (%) = 334 (4), 211 (19), 209 (11), 159 (20), 133
(29), 105 (100), 77 (30), 51 (11).
HRMS: m/z calcd for C16H11FO2Se [M
+
H]+: 331.0237; found:
334.9982.
MS (EI, 70 eV): m/z (%) = 296 (1), 239 (2), 174 (2), 159 (1), 118 (7), 105
(100), 77 (38), 51 (16).
HRMS: m/z calcd for C14H16O2Se [M + H]+: 297.0394; found: 297.0389.
3-{[3-(Trifluoromethyl)phenyl]selanyl}prop-2-yn-1-yl Benzoate
(3g)
Yield: 0.059 g (62%); yellow oil.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–M

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F. Gritzenco et al.
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Synthesis
4-Methyl-[3-(phenylselanyl)prop-2-yn-1-yl] Benzoate (3l)
HRMS: m/z calcd for C18H14O2Se [M + H]+: 343.0237; found: 343.0233.
Yield: 0.038 g (46%); yellow oil.
3-(Phenyltellanyl)prop-2-yn-1-yl Benzoate (3q)
1H NMR (CDCl3, 400 MHz):  = 7.89–7.87 (m, 2 H), 7.47–7.45 (m, 2 H),
Yield: 0.058 g (64%); yellow oil.
7.25–7.21 (m, 2 H), 7.20–7.14 (m, 3 H), 5.04 (s, 2 H), 2.32 (s, 3 H).
1H NMR (CDCl3, 400 MHz):  = 8.07–8.05 (m, 2 H), 7.71–7.68 (m, 2 H),
13C NMR (CDCl3, 100 MHz):  = 165.9, 144.0, 129.8, 129.5, 129.2,
7.57–7.52 (m, 1 H), 7.44–7.40 (m, 2 H), 7.27–7.22 (m, 3 H), 5.18 (s, 2
H).
13C NMR (CDCl3, 100 MHz):  = 165.7, 135.5, 133.2, 129.8, 129.7,
129.1, 128.0, 127.3, 126.7, 98.1, 68.0, 53.4, 21.6.
MS (EI, 70 eV): m/z (%) = 330 (3), 193 (16), 173 (15), 119 (100), 115
(30), 91 (24), 77 (8), 51 (9).
129.5, 128.3, 128.1, 112.2, 108.8, 53.7, 46.5.
HRMS: m/z calcd for C17H14O2Se [M + H]+: 331.0237; found: 331.0232.
MS (EI, 70 eV): m/z (%) = 365 (1), 244 (8), 159 (21), 131 (8), 114 (63),
105 (100), 77 (57), 51 (26).
HRMS: m/z calcd for C16H12O2Te [M + H]+: 366.9978; found: 366.9973.
2-Methoxy-[3-(phenylselanyl)prop-2-yn-1-yl] Benzoate (3m)
Yield: 0.052 g (60%); yellow oil.
1H NMR (CDCl3, 400 MHz):  = 6.59–6.57 (m, 1 H), 6.28–6.27 (m, 1 H),
6.26–6.25 (m, 1 H), 6.22–6.17 (m, 1 H), 6.05–6.01 (m, 2 H), 5.99–5.97
(m, 1 H), 5.71–5.68 (m, 2 H), 3.84 (s, 2 H), 2.61 (s, 3 H).
3-(Butyltellanyl)prop-2-yn-1-yl Benzoate (3r)
Yield: 0.034 g (40%); yellow oil.
1H NMR (CDCl3, 400 MHz):  = 8.08–8.06 (m, 2 H), 7.58–7.54 (m, 1 H),
7.46–7.42 (m, 2 H), 5.15 (s, 2 H), 2.84 (t, J = 7.4 Hz, 2 H), 1.86 (quint, J =
7.5 Hz, 2 H), 1.42 (sext, J = 7.4 Hz, 2 H), 0.93 (t, J = 7.3 Hz, 3 H).
13C NMR (CDCl3, 100 MHz):  = 165.1, 159.4, 133.9, 131.8, 129.5,
129.1, 128.0, 127.2, 120.0, 119.1, 112.0, 98.1, 67.8, 55.9, 53.3.
MS (EI, 70 eV): m/z (%) = 346 (1), 194 (12), 193 (12), 189 (9), 135
(100), 115 (37), 92 (7), 77 (22), 51 (11).
13C NMR (CDCl3, 100 MHz):  = 165.8, 133.1, 129.8, 128.3, 105.8 74.9,
53.8, 43.2, 33.6, 24.6, 13.2, 9.6.
HRMS: m/z calcd for C17H14O3Se [M + H]+: 347.0186; found: 347.0182.
MS (EI, 70 eV): m/z (%) = 346 (1), 289 (3), 287 (3), 168 (16), 105 (100),
77 (31), 51 (9), 29 (22).
HRMS: m/z calcd for C14H16O2Te [M + H]+: 347.0291; found: 347.0286.
4-Fluoro-N-[3-(phenylselanyl)prop-2-yn-1-yl] Benzoate (3n)
Yield: 0.072 g (87%); yellow oil.
1H NMR (CDCl3, 400 MHz):  = 8.12–8.07 (m, 2 H), 7.55–7.52 (m, 2 H),
76.34–7.24 (m, 3 H), 7.14–7.09 (m, 2 H), 5.13 (s, 2 H).
Bis[3-(phenylselanyl)prop-2-yn-1-yl] Adipate (3u) (Scheme 2)
Yield: 0.061 g (46%); yellow oil.
13C NMR (CDCl3, 100 MHz):  = 167.2, 164.8 (d, 1JC,F = 233.2 Hz), 132.4
1H NMR (CDCl3, 400 MHz):  = 7.53–7.50 (m, 4 H), 7.33–7.27 (m, 6 H),
4.91 (s, 2 H), 4.88 (s, 2 H), 2.69–2.62 (m, 4 H), 2.53–2.48 (m, 2 H),
2.37–2.33 (m, 2 H).
13C NMR (CDCl3, 100 MHz):  = 172.4, 169.9, 162.7, 160.7, 129.5,
129.1, 127.9, 127.3, 117.5, 117.4, 98.0, 97.9, 68.0, 67.9, 53.0, 52.9,
33.6, 29.3, 24.1, 23.8.
3
4
(d, JC,F = 9.4 Hz), 129.6, 129.3, 127.9, 127.4, 125.7 (d, JC,F = 2.9 Hz),
115.6 (d, 2JC,F = 22.1 Hz), 97.7, 68.5, 53.7.
MS (EI, 70 eV): m/z (%) = 334 (4), 254 (1), 193 (20), 177 (26), 123
(100), 95 (35), 75 (15), 51 (20).
HRMS: m/z calcd for
C16H11FO2Se [M +
H]+: 334.9986; found:
334.9982.
HRMS: m/z calcd for
C22H22O4Se2 [M +
H]+: 534.9927; found:
534.9926.
3-(Phenylselanyl)prop-2-yn-1-yl Nicotinate (3o)
Yield: 0.048 g (60%); yellow oil.
Propynyl Benzoates 4a–f via Suzuki-Type Reaction;17b General Pro-
cedure
1H NMR (CDCl3, 400 MHz):  = 9.26–9.25 (m, 1 H), 8.79–8.77 (dd, J =
4.9, 1.7 Hz, 1 H), 8.33–8.30 (m, 1 H), 7.55–7.52 (m, 2 H), 7.40–7.36 (m,
1 H), 7.34–7.29 (m, 2 H), 7.30–7.25 (m, 1 H), 5.17 (s, 2 H).
13C NMR (CDCl3, 100 MHz):  = 164.5, 153.6, 151.0, 137.1, 129.5,
129.4, 127.8, 127.4, 125.5, 123.2, 97.3, 69.0, 53.9.
A mixture of 3-(butylselanyl)prop-2-yn-1-yl benzoate (3k; 74 mg,
0.25 mmol), Pd(PPh3)4 (29 mg, 10 mol%), and the proper boronic acid
(2.0 equiv) were dissolved in DMF (3 mL). After that, Cu(OAc)2·H2O (60
mg, 0.3 mmol, 1.2 equiv) was added. This mixture was then heated in
an oil bath for 12 h at 80 °C. After this, the reaction was cooled to r.t.,
diluted with EtOAc (3 mL), and then washed with sat. aq NH4Cl (20
mL). The organic phase was separated, dried (MgSO4), and concen-
trated under vacuum. The residue was purified by flash chromatogra-
phy eluting with hexane/EtOAc.
MS (EI, 70 eV): m/z (%) = 318 (2), 317 (10), 211 (8), 193 (24), 160 (43),
117 (11), 106 (100), 78 (44), 51 (26).
HRMS: m/z calcd for C15H11NO2Se [M + H]+: 318.0033; found:
318.0028.
3-(Phenylselanyl)prop-2-yn-1-yl Cinnamate (3p)
3-(Phenyl)prop-2-yn-1-yl Benzoate (4a)
Yield: 0.078 g (92%); yellow oil.
Yield: 0.030 g (52%); colorless oil.
1H NMR (CDCl3, 400 MHz):  = 8.12–8.09 (m, 2 H), 7.60–7.56 (m, 1 H),
7.49–7.44 (m, 4 H), 7.34–7.31 (m, 3 H), 5.16 (s, 2 H).
13C NMR (CDCl3, 100 MHz):  = 165.9, 159.9, 133.4, 133.2, 129.8,
1H NMR (CDCl3, 400 MHz):  = 7.65 (d, J = 16.0 Hz, 1 H), 7.46–7.45 (m,
1 H), 7.44–7.40 (m, 3 H), 7.30–7.27 (m, 3 H), 7.25–7.14 (m, 3 H), 6.37
(d, J = 16.0 Hz, 1 H), 4.94 (s, 2 H).
13C NMR (CDCl3, 100 MHz):  = 166.0, 145.7, 134.1, 130.4, 129.5,
129.3, 128.8, 128.1, 127.9, 127.3, 117.1, 97.9, 68.1, 53.1.
128.4, 114.2, 113.9, 86.6, 81.7, 55.2, 53.5.
MS (EI, 70 eV): m/z (%) = 237 (5), 236 (31), 114 (89), 105 (100), 89 (8),
77 (32), 63 (8), 51 (14).
HRMS: m/z calcd for C16H12O2 [M + H]+: 237.0915; found: 237.0910.
MS (EI, 70 eV): m/z (%) = 342 (6), 314 (15), 281 (39), 253 (23), 207
(100), 157 (26), 117 (4), 77 (26), 51 (12).
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–M

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F. Gritzenco et al.
Paper
Synthesis
3-(4-Chlorophenyl)prop-2-yn-1-yl Benzoate (4b)
Propynyl Benzoate via Sonogashira-Type Reaction;17b 6-Hydroxy-
6-methylhepta-2,4-diyn-1-yl Benzoate (5a)
Yield: 0.056 g (83%); pale yellow oil.
A mixture of 3-(butylselanyl)prop-2-yn-1-yl benzoate (3k; 74 mg,
0.25 mmol), PdCl2(PPh3)2 (18 mg, 10 mol%), 2-methylbut-3-yn-2-ol
(84 mg, 1 mmol, 4 equiv), and Et3N (101 mg, 1 mmol, 4.0 equiv) were
dissolved in DMF (3 mL). After that, Cu(OAc)2·H2O (10 mg, 20 mol%)
was added. The Schlenk tube was then heated in an oil bath for 24 h at
80 °C. Then, the reaction was cooled to r.t., the crude reaction mixture
was diluted with EtOAc (3 mL) and then washed with sat. aq NH4Cl
(20 mL). The organic phase was separated, dried (MgSO4), and con-
centrated under vacuum. The residue was purified by flash chroma-
tography and eluted with a mixture of hexane/EtOAc; yield: 0.030 g
(50%); colorless oil.
1H NMR (CDCl3, 400 MHz):  = 8.12–8.10 (m, 2 H), 7.61–7.57 (m, 1 H),
7.49–7.45 (m, 2 H), 7.42–7.40 (m, 2 H), 7.31–7.27 (m, 2 H), 5.14 (s, 2
H).
13C NMR (CDCl3, 100 MHz):  = 165.9, 133.3, 133.1, 129.8, 129.5,
128.7, 128.4, 84.1, 60.4, 53.2, 21.0, 14.2.
MS (EI, 70 eV): m/z (%) = 271 (3), 270 (15), 242 (6), 148 (56), 113 (16),
105 (100), 77 (24), 51 (11).
3-(4-Tolyl)prop-2-yn-1-yl Benzoate (4c)
Yield: 0.054 g (87%); white solid; mp 47-49 ºC.
1H NMR (CDCl3, 400 MHz):  = 8.07–8.04 (m, 2 H), 7.60–7.56 (m, 1 H),
7.47–7.43 (m, 2 H), 4.97 (s, 2 H), 2.16 (s, 1 H), 1.53 (s, 6 H).
13C NMR (CDCl3, 100 MHz):  = 165.7, 133.4, 129.8, 129.3, 128.4, 84.1,
1H NMR (CDCl3, 400 MHz):  = 8.11–8.10 (m, 1 H), 8.09–8.08 (m, 1 H),
7.58–7.54 (m, 1 H), 7.46–7.42 (m, 2 H), 7.37–7.35 (m, 2 H), 7.12–7.10
(m, 2 H), 5.14 (s, 2 H), 2.34 (s, 3 H).
73.5, 70.7, 66.3, 65.5, 52.9, 31.0.
13C NMR (CDCl3, 100 MHz):  = 165.9, 138.9, 133.2, 131.8, 129.8,
129.0, 128.4, 119.1, 86.8, 82.4, 53.4, 29.7, 21.4.
MS (EI, 70 eV): m/z (%) = 243 (2), 242 (15), 120 (5), 105 (100), 91 (7),
77 (42), 65 (2), 51 (11).
MS (EI, 70 eV): m/z (%) = 251 (6), 250 (33), 222 (11), 128 (100), 115
(10), 105 (84), 77 (38), 51 (13).
HRMS: m/z calcd for C17H14O2 [M + H]+: 251.1072; found: 251.1067.
In vitro Anticancer Assay
Human GBM cell line A172, obtained from American Tissue Culture
Collection (ATCC, Rockville, MD) was kindly provided by Dr. Guido
Lenz (Department of Biophysics, Federal University of Rio Grande do
Sul (UFRGS), Brazil). All culture material and reagents were purchased
from Gibco Laboratories (Grand Island, NY, USA). Cells were cultured
in DMEM low glucose supplemented with 10% of Fetal Bovine Serum
(FBS), 1% penicillin/streptomycin, and 0.1% amphotericin B at 37 °C
and 5% CO2 in a humidified incubator.
3-(4-Methoxyphenyl)prop-2-yn-1-yl Benzoate (4d)
Yield: 0.030 g (46%); white solid; mp 35-37 ºC.
1H NMR (CDCl3, 400 MHz):  = 8.07–8.04 (m, 2 H), 7.57–7.52 (m, 1 H),
7.50–7.46 (m, 2 H), 7.44–7.40 (m, 2 H), 6.87–6.83 (m, 2 H), 5.08 (s, 2
H), 3.76 (s, 3 H).
13C NMR (CDCl3, 100 MHz):  = 165.7, 159.6, 135.3, 133.1, 132.2,
Glioma cells were seeded at 5 × 104 cells/well in DMEM/10% FBS in
24-well plates. After reaching subconfluence, the cultures were ex-
posed to 3-(phenylselanyl)prop-2-yn-1-yl benzoate (3a) at concentra-
tions of 1, 10, 50, or 100 M and Tmz (Sigma-Aldrich Chemical Co.,
St.Louis, MO, USA) at concentration 30 M, both compounds dissolved
in DMSO at different times (24, 48 and 72 h). Control cultures were
performed with DMSO (at maximum 0.5% final concentration). At the
end of the treatment, cells were counted in a hemocytometer and the
number of cells present in the control group was considered as 100%.
Statistical analysis was conducted by ANOVA followed by Tukey post-
hoc test to multiple comparisons of at least three independent exper-
iments. p-Value under 0.05 was considered significant.
129.7, 129.5, 128.3, 117.3, 115.3, 114.7, 96.3, 69.3, 55.3, 53.5.
MS (EI, 70 eV): m/z (%) = 267 (10), 266 (55), 238 (12), 144 (100), 115
(15), 105 (73), 77 (30), 51 (12).
HRMS: m/z calcd for C17H14O3 [M + H]+: 267.1021; found: 267.1016.
3-(2-Methoxyphenyl)prop-2-yn-1-yl Benzoate (4e)
Yield: 0.034 g (52%); colorless oil.
1H NMR (CDCl3, 400 MHz):  = 8.11–8.09 (m, 2 H), 7.58–7.53 (m, 1 H),
7.45–7.42 (m, 3 H), 7.31–7.25 (m, 1 H), 6.91–6.85 (m, 2 H), 5.20 (s, 2
H), 3.87 (s, 3 H).
13C NMR (CDCl3, 100 MHz):  = 165.9, 160.4, 134.0, 133.1, 130.2,
129.8, 128.4, 128.3, 120.4, 111.5, 110.8, 87.0, 83.0, 55.8, 53.6.
MS (EI, 70 eV): m/z (%) = 267 (4), 266 (21), 238 (13), 144 (24), 115
(82), 105 (100), 77 (34), 51 (11).
Conflict of Interest
The authors declare no conflict of interest
HRMS: m/z calcd for C17H14O3 [M + H]+: 267.1021; found: 267.1016.
3-(Naphthalen-2-yl)prop-2-yn-1-yl Benzoate (4f)
Funding Information
Yield: 0.040 g (58%); colorless oil.
Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul
(PRONEM 16/2551-0000240-1 and PRONEX 16/2551) and Conselho
Nacional de Desenvolvimento Científico e Tecnológico (Universal -
Processo 428193/2018-8). This study was financed in part by the
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior -
1H NMR (CDCl3, 400 MHz):  = 8.15–8.12 (m, 2 H), 7.84 (d, 2 H, J = 8.42
Hz), 7.72–7.70 (m, 1 H), 7.60–7.56 (m, 2 H), 7.53–7.40 (m, 4 H), 7.25
(s, 1 H), 5.31 (s, 2 H).
13C NMR (CDCl3, 100 MHz):  = 166.0, 133.5, 133.2, 133.1, 131.0,
129.9, 129.8, 129.3, 128.4, 128.3, 126.9, 126.5, 126.1, 125.1, 119.9,
87.9, 84.8, 53.5.
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MS (EI, 70 eV): m/z (%) = 287 (4), 286 (19), 258 (7), 164 (78), 152 (12),
105 (100), 77 (26), 51 (8).
HRMS: m/z calcd for C20H14O2 [M + H]+: 287.1072; found: 287.1066.
Acknowledgment
We are grateful to the academic institutions which have provided the
laboratorial support.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–M

L
F. Gritzenco et al.
Paper
Synthesis
Supporting Information
(18) (a) Srivastava, K.; Panda, A.; Sharma, S.; Singh, H. B.
J. Organomet. Chem. 2018, 861, 174. (b) Lu, X.; Mestres, G.;
Singh, V. P.; Effati, P.; Poon, J.-F.; Engman, L.; Ott, M. K. Antioxi-
dants 2017, 6, 13. (c) Reddy, L. M.; Lavanya, G.; Teja, G. L.;
Padmaja, A.; Padmavathi, V. J. Heterocycl. Chem. 2017, 54, 2755.
(d) Petragnani, N.; Stefani, H. A. Tellurium in Organic Synthesis,
2nd ed.; Academic Press: London, 2007.
Supporting information for this article is available online at
https://doi.org/10.1055/a-1477-6470.
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References
(19) Beletskaya, I. P.; Ananikov, V. P. Chem. Rev. 2011, 111, 1596.
(20) (a) Xaviera, M. C. D. F.; Goldania, B.; Schumacher, R. F.; Perin, G.;
Schneider, P. H.; Alves, D. J. Mol. Catal. A: Chem. 2017, 427, 73.
(b) Godoi, M.; Liz, D. G.; Ricardo, E. W.; Rocha, M. S. T.; Azeredo,
J. B.; Braga, A. L. Tetrahedron 2014, 70, 3349. (c) Rampon, D. S.;
Giovenardi, R.; Silva, T. L.; Rambo, R. S.; Merlo, A. A.; Schneider,
P. H. Eur. J. Org. Chem. 2011, 7066.
(21) (a) Balbom, E. B.; Gritzenco, F.; Sperança, A.; Godoi, M.; Alves,
D.; Barcellos, T.; Godoi, B. Tetrahedron 2019, 75, 4017.
(b) Movassagh, B.; Mohammadi, E. Curr. Green Chem. 2016, 3,
18. (c) Mohan, B.; Hwang, S.; Woo, H.; Park, K. H. Synthesis 2015,
47, 3741. (d) Godoi, M.; Ricardo, E. W.; Frizon, T. E.; Rocha, M. S.
T.; Singh, D.; Paixão, M. W.; Braga, A. L. Tetrahedron 2012, 68,
10426. (e) Bieber, L. W.; da Silva, M. F.; Menezes, P. H. Tetrahe-
dron Lett. 2004, 45, 2735.
(22) (a) Wu, Y.; Huang, Z.; Luo, Y.; Deng, Y.; Yi, H.; Lee, J.-F.; Pao, C.-
W.; Chen, J.-L.; Lei, A. Org. Lett. 2017, 19, 2330. (b) Karimi, B.;
Hazarkhani, H.; Zareyee, D. Synthesis 2002, 2513.
(23) (a) Sova, M. Mini Rev. Med. Chem. 2012, 12, 749. (b) Lin, Y.-S.;
Chen, S.-H.; Huang, W.-J.; Chen, C.-H.; Chien, M.-Y.; Lin, S.-Y.;
Hou, W. C. Food Chem. 2012, 132, 2074. (c) Chen, D.-D.; Zhang,
B.-Y.; Liu, X.-X.; Li, X.-Q.; Yang, X.-J.; Zhou, L. Bioorg. Med. Chem.
Lett. 2018, 28, 1149. (d) Narang, R.; Narasimhan, B.; Sharma, S.;
Sriram, D.; Yogeeswari, P.; Clercq, E. D.; Pannecouque, C.;
Balzarini, J. Med. Chem. Res. 2012, 21, 1557.
(24) (a) Ananikov, V. P.; Gayduk, K. A.; Beletskaya, I. P.; Khrustalev, V.
N.; Antipin, M. Y. Eur. J. Inorg. Chem. 2009, 1149. (b) Ananikov,
V. P.; Gayduk, K. A.; Beletskaya, I. P.; Khrustalev, V. N.; Antipin,
M. Y. Chem. Eur. J. 2008, 14, 2420.
(25) (a) Movassagh, B.; Yousefi, A.; Momeni, B. Z.; Heydari, S. Synlett
2014, 25, 1385. (b) Ranu, B. C.; Dey, R.; Chatterjee, T.;
Ahammed, S. ChemSusChem 2012, 5, 22.
(26) (a) Liu, J.; Lam, J. W. Y.; Tang, B. Z. Chem. Rev. 2009, 109, 5799.
(b) Siemsen, P.; Livingston, R. C.; Diederich, F. Angew. Chem. Int.
Ed. 2000, 39, 2632.
(27) (a) Sancineto, L.; Palomba, M.; Bagnoli, L.; Marini, F.; Santi, C.
Curr. Org. Chem. 2015, 20, 122. (b) Nomoto, A.; Ogawa, A. In The
Chemistry of Organic Selenium and Tellurium Compounds;
Rappoport, Z., Ed.; Wiley: Chichester, 2014.
(1) (a) Chen, H.; Li, B.; Zhang, M.; Lu, H.; Wang, Y.; Wang, W.; Ding,
Y.; Hu, A. ChemistrySelect 2020, 5, 7069. (b) Hong, J.; Zeng, X.-A.;
Brennan, C. S.; Brennan, M.; Han, Z. Foods 2016, 5, 50. (c) Neta,
N. S.; Teixeira, J. A.; Rodrigues, L. R. Crit. Rev. Food Sci. Nutr. 2015,
55, 595.
(2) Farooq, S.; Ngaini, Z. Curr. Organocatal. 2018, 5, 205.
(3) Wang, Y. J.; Xiong, L. D.; Song, C. W.; Li, L.; Li, Y.; Dong, L.; Yin, S.
F. Chem. Nat. Comp. 2014, 50, 598.
(4) Zhu, G.; Zhang, G. ChemistrySelect 2020, 5, 9153.
(5) (a) Kaushik, C. P.; Pahwa, A.; Kumar, D.; Kumar, A.; Singh, D.;
Kumar, K.; Luxmi, R. J. Heterocycl. Chem. 2018, 55, 1720.
(b) Krátký, M.; Vinšová, J.; Novotná, E.; Mandíková, J.; Trejtnar,
F.; Stolaríková, J. Molecules 2013, 18, 3674.
(6) (a) Larson, N.. R.; Zhang, A.; Feldlaufer, M.. F. J. Med. Entomol.
2020, 57, 187. (b) Elabasy, A.; Shoaib, A.; Waqas, M.; Jiang, M.;
Shi, Z. Molecules 2019, 24, 2801.
(7) Attalah, K. M.; Abdalla, A. N.; Aslam, A.; Ahmed, M.; Abourehab,
M. A. S.; ElSawy, N. A.; Gouda, A. M. Bioorg. Chem. 2020, 94,
103371.
(8) Zou, H.; Chen, G.; Zhou, S. RSC Adv. 2019, 9, 6627.
(9) Fukushi, Y.; Yoshino, H.; Ishikawa, J.; Sagisaka, M.; Kashiwakura,
I.; Yoshizawa, A. J. Mater. Chem. B 2014, 2, 1335.
(10) (a) Reich, H. J.; Hondal, R. J. ACS Chem. Biol. 2016, 11, 821.
(b) Orian, L.; Toppo, S. Free Radic. Biol. Med. 2014, 66, 65.
(c) Tiekink, E. R. Dalton Trans. 2012, 41, 6390. (d) Prigol, M.;
Bruning, C. A.; Godoi, B.; Nogueira, C. W.; Zeni, G. Pharmacol.
Rep. 2009, 61, 1127. (e) Nogueira, C. W.; Zeni, G.; Rocha, J. B.
Chem. Rev. 2004, 104, 6255.
(11) (a) Singh, B. G.; Kumar, P.; Phadnis, P.; Iwaoka, M.; Priyadarsini,
K. I. New J. Chem. 2019, 43, 13357. (b) Bandeira, P. T.; Dalmolin,
M. C.; de Oliveira, M. M.; Nunes, K. C.; Garcia, F. P.; Nakamura, C.
V.; de Oliveira, A. R. M.; Piovan, L. Bioorg. Med. Chem. 2019, 27,
410.
(12) (a) Yavuz, S.; Ozkan, H.; Gurel, O.; Yildirir, Y. Gazi University J.
Sci. 2016, 29, 309. (b) Ananth, D. A.; Rameshkumar, A.; Jeyadevi,
R.; Jagadeeswari, S.; Nagarajan, N.; Renganathan, R.; Sivasudha,
T. Spectrochim. Acta, Part A. 2015, 138, 684 .
(13) Anversa, R. G.; Sousa F, S. S.; Birmann, P. T.; Lima, D. B.;
Lenardão, E. J.; Bruning, C. A.; Savegnago, L. J. Pharm. Pharmacol.
2018, 70, 901.
(14) Okoronkwo, A. E.; Godoi, B.; Schumacher, R. F.; Neto, J. S. S.;
Luchese, C.; Prigol, M.; Nogueira, C. W.; Zeni, G. Tetrahedron Lett.
2009, 50, 909.
(15) (a) Wu, C. H.; Shi L, X.; Li Q, N.; Jiang, H.; Selke, M.; Yan, H.;
Wang, X. M. Nanomed. Nanotechnol. Biol. Med. 2012, 8, 860.
(b) Novotny, L.; Rauko, P.; Kombian, S. B.; Edafiogho, I. O. Neo-
plasma 2010, 5, 383.
(16) (a) Stazi, A. V.; Trinti, B. Minerva Med. 2008, 99, 643. (b) Ursini,
F.; Bindoli, A. Chem. Phys. Lipids 1987, 44, 255.
(17) (a) Kazmierczak, J. C.; Recchi, A. M. S.; Gritzenco, F.; Balbom, E.
B.; Barcellos, T.; Speranca, A.; Godoi, B. Eur. J. Org. Chem. 2017,
6382. (b) Stein, A. L.; Bilheri, F. N.; Zeni, G. Chem. Commun.
2015, 51, 15522.
(28) (a) Yan, Z.; Yuan, X.-A.; Zhao, Y.; Zhu, C.; Xie, J. Angew. Chem. Int.
Ed. 2018, 57, 12906. (b) Li, X.; Xie, X.; Sun, N.; Liu, Y. Angew.
Chem. Int. Ed. 2017, 56, 6994.
(29) Ostrom, Q. T.; Gittleman, H.; Liao, P.; Vecchione-Koval, T.;
Wolinsky, Y.; Kruchko, C.; Barnholtz-Sloan, J. Neuro Oncol. 2017,
19 (Suppl. 5), v1.
(30) Stupp, R.; Mason, W. P.; van den Bent, M. J.; Weller, M.; Fisher,
B.; Taphoorn, M. J.; Belanger, K.; Brandes, A. A.; Marosi, C.;
Bogdahn, U.; Curschmann, J.; Janzer, R. C.; Ludwin, S. K.; Gorlia,
T.; Allgeier, A.; Lacombe, D.; Cairncross, J. G.; Eisenhauer, E.;
Mirimanoff, R. O. N. Engl. J. Med. 2005, 352, 987.
(31) Wainwright, D. A.; Nigam, P.; Thaci, B.; Dey, M.; Lesniak, M. S.
Expert Opin. Emerg. Drugs 2012, 17, 181.
(32) Tran, B.; Rosenthal, M. A. J. Clin. Neurosci. 2010, 17, 417.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–M

M
F. Gritzenco et al.
Paper
Synthesis
(33) Doering, M.; Ba, L. A.; Lilienthal, N.; Nicco, C.; Scherer, C.; Abbas,
M.; Zada, A. A. P.; Coriat, R.; Burkholz, T.; Wessjohann, L.;
Diederich, M.; Batteux, F.; Herling, M.; Jacob, C. J. Med. Chem.
2010, 53, 6954.
(34) de Souza, D.; Mariano, D. O. C.; Nedel, F.; Schultze, E.; Campos,
V. F.; Seixas, F.; da Silva, R. S.; Munchen, T. S.; Ilha, V.; Dornelles,
L.; Braga, A. L.; Rocha, J. B. T.; Collares, T.; Rodrigues, O. E. D.
J. Med. Chem. 2015, 58, 3329.
(37) Lilienthal, N.; Prinz, C.; Peer-Zada, A. A.; Doering, M.; Ba, L. A.;
Hallek, M.; Jacob, C.; Herling, M. Leuk. Lymphoma 2011, 52,
1407.
(38) Ferreira, L. M.; Azambuja, J. H.; da Silveira, E. F.; Sari, M. H. M.;
Fulco, B. C. W.; Prado, V. C.; Gelsleichter, N. E.; Beckenkamp, L.
R.; Fernandes, M. C.; Spanevello, R. M.; Wink, M. R.; Alves, R. C.
S.; Nogueira, C. W.; Braganhol, E.; Cruz, L. J. Trace Elem. Med.
Biol. 2019, 55, 180.
(35) Yadav, S.; Singh, J. D. J. Biomol. Struct. Dyn. 2019, 37, 3337.
(36) Banerjee, K.; Padmavathi, G.; Bhattacherjee, D.; Saha, S.;
Kunnumakkara, A. B.; Bhabak, K. P. Org. Biomol. Chem. 2018, 16,
8769.
(39) Zhang, Y.; Zheng, S.; Ngai, S. M.; Zheng, W.; Chen, J.; Li, T.;
Zhong, X. Chem. Pharm. Bull. 2014, 62, 994.
(40) Nogueira, C. W.; Rocha, J. B. Arch. Toxicol. 2011, 85, 1313.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–M