Novel functionalized organotellurides with enhanced thiol peroxidase catalytic activity

Article abstract of DOI:10.1039/c8nj00700d

The thiol peroxidase-like activity of a series of novel functionalized tellurium containing catalysts has been investigated with different models. Dialkyl- and aryl-alkyl-tellurides, conveniently achieved through the ring opening of strained heterocycles, exhibited remarkable catalytic antioxidant activity, being able to reduce hydrogen peroxide in the presence of different thiols (benzenethiol, dithiothreitol and glutathione) under different conditions. The nature of the β-substituent strongly influenced the performances of the studied catalysts, thus giving useful criteria for the design of good synthetic mimics of glutathione peroxidase. The catalytic activity of functionalized organotellurides has been compared with that of their selenated analogues, showing as the latter behave as less efficient catalysts.

Full text of DOI:10.1039/c8nj00700d

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PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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DOI: 10.1039/C8NJ00700D
Journal Name
ARTICLE
Novel functionalized organotellurides with enhanced thiol
peroxidase catalytic activity
Received 00th January 20xx,
Accepted 00th January 20xx
Damiano Tanini*a, Anna Grechia, Lorenzo Riccia, Silvia Deib, Elisabetta Teodorib, Antonella
Capperucci*a
DOI: 10.1039/x0xx00000x
The thiol peroxidase-like activity of a series of novel functionalized tellurium containing catalysts has been investigated
with different models. Dialkyl- and aryl-alkyl-tellurides, conveniently achieved through the ring opening of strained
heterocycles, exhibited remarkable catalytic antioxidant activity, being able to reduce hydrogen peroxide in the presence
of different thiols (benzenethiol, dithiothreitol and glutathione) under different conditions. The nature of the β-
substituent strongly influenced the performances of the studied catalysts, thus giving useful criteria for the design of good
synthetic mimics of glutathione peroxidase. The catalytic activity of functionalized organotellurides has been compared
with that of their selenated analogues, showing as the latter behave as less efficient catalysts.
www.rsc.org/
exhibit thiol peroxidase activity against different thiols.
Several authors have described that substitution of selenium by
tellurium in a series of diarylchalcogenides results in a pronounced
Introduction
Glutathione peroxidase (GPx) is
a selenocysteine-containing
increase of the catalytic antioxidant activity.1c
mammalian enzyme that plays a crucial role in the protection of
aerobic living cells from oxidative stress. It catalyzes the reduction
of harmful hydroperoxides by using glutathione (GSH) as a reducing
agent.1
The onset of a number of human diseases such as cancer, cystic
fibrosis, immune disorders, atherosclerosis, Alzheimer's and
Parkinson's disease has been correlated with an enhanced
concentration of reactive oxygen species (ROS), due to oxidative
stress.2 Taking into account the importance of glutathione
peroxidase as a natural defence against oxidative stress, the design
and the synthesis of novel small molecules active as catalytic
antioxidants have attracted considerable interest.3
The
catalytic
activity
of
5-hydroxy-2,3-
dihydrobenxo[b]tellurophene11, aryl-telluroamino derivatives12 and
tellurium functionalised cyclodextrine13 have also been studied. On
the other hand, the introduction of tellurium containing moieties
onto natural compounds such as tocopherols14 and chrysin15 have
been applied to increase the antioxidant activity of such structures.
Substituted dialkyl ditellurides have received less attention with
respect to their diaryl analogues8,12,16 albeit their potential interest
in developing new pharmacological agents. Furthermore, the
promising pharmacological properties of N- and O-containing
organochalcogens have prompted researchers to design novel
heteroatom-functionalized chalcogenides.17 To the best of our
knowledge, a little is known about the GPx-like properties of
hydroxy- or amino-functionalized dialkyl- and aryl-alkyl- tellurides,
whereas no example is reported for organotellurides bearing
sulfurated moieties.12,18
Over the past decades, after the discovery that ebselen mimics the
catalytic activity of GPx, several synthetic organoselenium
compounds have emerged as good GPx-like active compounds,
being able to reduce peroxides using thiols as cofactors.4,5
In recent years, besides organoselenium derivatives, the design and
synthesis of Te-containing antioxidant compounds has attracted
considerable attention as some of them exhibited antitumor,
During the course of our studies in the selenium chemistry we
disclosed novel synthetic routes to access several classes of new
functionalized organoselenium derivatives through the ring opening
reaction of strained heterocycles with selenosilanes.19,20 Some of
these selenium-containing structures showed interesting activities
as antioxidants21 and carbonic anhydrase inhibitors.22 More
recently, we extended our interest to the tellurium chemistry,
finding a convenient approach to functionalized dialkyl- and aryl-
alkyl- tellurides.23 Indeed, reaction of epoxides, aziridines and
thiiranes with Li2Te leads to the smooth formation of β-hydroxy-
dialkyl tellurides, β-amino-dialkyl tellurides and disubstituted 1,2,5-
dithiatellurepanes through a regioselective and stereospecific ring
antibacterial, and antihelmenthic activities6.
A number of
organotellurium derivatives have been reported as GPx mimics.1c,7
Diaryl tellurides8,9 and ditellurides10 have been demonstrated to
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J. Name., 2013, 00, 1-3 | 1
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ARTICLE
Journal Name
opening route. Furthermore, β-phenyltelluro- alcohols, amines and
disulfides can be achieved from the above mentioned strained
heterocycles by using either in situ generated PhTe− or PhTeSiMe3,
View Article Online
DOI: 10.1039/C8NJ00700D
through
a fluoride ion mediated ring opening reaction in
comparable yields23.
These methodologies might offer the possibility to design new
variously functionalized biologically active molecules.24 As a part of
our growing interest in the study of novel antioxidant systems, we
report herein the data obtained in the investigation of the thiol-
peroxidase-like activity of a series of functionalized tellurides.
Results and discussion
Figure 1: Oxidation of DTTred with H2O2 in the presence of Te-
containing catalysts (1%). Reaction conditions: [DTTred]0=0.14 mM,
[H2O2]0=0.14 mM, [catalyst]=0.0014 mM), CD3OD (0.6 mL). In the
control experiment the reaction was run with no catalyst. The mean
± SD values of three separate experiments are reported.
Organotellurides reported in Chart 1 were synthesised from three-
membered heterocycles as reported in the Scheme S1 (ESI).23
The catalytic antioxidant activity of these densely functionalised
organotellurium compounds as GPx model enzymes was studied
according to literature reported methods using dithiothreitol,25
benzenethiol26 or glutathione27 as substrates.
With the aim to enlarge the scope of the study, the β-phenyltelluro
alcohol 3c – containing two tellurium atoms - was conveniently
synthesized from 1,3-butadiene diepoxide (Scheme 1) and tested
under the above reported conditions. As can be noticed from Fig. 1,
the thiol-peroxidase-like activity showed by 3c resulted about
three-fold higher than 3b.
The catalytic thiol-peroxidase activity of compounds 1-7 was
preliminary investigated following the dithiothreitol (DTTred
)
1
oxidation by means of H NMR. Methanol (CD3OD) was selected as
a solvent in this assay because the reaction proceeded too fast in
water.
We commenced our studies with hydroxy telluride 1a. We were
pleased to observe an immediate and complete oxidation of DTT,
when this compound was used in catalytic amount (10 mol % with
respect to DTT). Intriguingly, the same excellent activity was
retained when the test was performed with a lower concentration
of 1a (1 mol %, Figure 1). On the basis of these findings, the activity
of a series of hydroxy tellurides (1-3) was investigated under the
same conditions. As can be seen from the graph depicted in Figure
1, symmetric β-hydroxy tellurides 1a-c exhibited a remarkable
O
OH
NaBH4
O
Ph2Te2
PhTe
PhTe
0
1h
°C,
EtOH
TePh
r.t.
0 °C to
3 h
79%
3c,
OH
Scheme 1
Having explored the thiol-peroxidase-like activity of variously
catalytic activity, promoting complete DTT oxidation within 2 min substituted β-hydroxy tellurides, we moved to evaluate whether
from the addition of H2O2. In order to evaluate the influence of the such catalytic activity could be affected by the nature of the
functional group present at the β positio. Thus, differently
substituted tellurides 4-7, bearing a β-amino or a β-disulfide moiety
were used as catalysts in the reaction of DTT with H2O2. As can be
seen in the Figure 2, the β-amino dialkyl telluride 4 behaved as the
most active catalyst within this series, although the β-hydroxy
substituted analogues 1a-c performed marginally better under the
same conditions. On the other hand, β-phenyltelluro- amine 5 and
Te-containing moiety on the GPx-like activity of β-hydroxy
tellurides, non-symmetric 2-hydroxy substituted- ethyl telluride 2
and phenyl tellurides 3a,b were used as catalysts. The curves
related to their efficacy are reported in Figure 1. These compounds
displayed a slightly lower activity than dihydroxy tellurides 1a-c,
catalyzing the complete DTT oxidation in 5-8 min.
OH
OH
:
OH
OH
OH
PhTe
Te
Te
PhTe
TePh
R
R
R
R
OH
3c
1a
2
3a
3b
R=CH2OBn
R=CH2OAll
R=Me
:R=CH2OBn
:R=CH2OBn
:R=Me
:
1b
:
1c
R
S
S
S
TePh
S
Ts
Te
Ts
PhTe
Ts
PhTe
N
H
N
N
Te
H
H
R
4
5
7
6
:R=CH2OBn
1
Chart
2 | J. Name., 2018, 00, 1-3
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disulfide 6 displayed a significant lower catalytic activity with sulfide 11 were synthesised from the correspoVniedwinAgrticlNe -OBnolince-
DOI: 10.1039/C8NJ00700D
protected aziridine and thiirane, following the Scheme 2. The amino
telluride 9 was obtained through acetyl chloride promoted cleavage
of the N-Boc protected phenyltelluro amine 8, arisen from a
regioselective ring opening reaction of the N-Boc 2-
isopropylaziridine with diphenyl ditelluride. S-allylation of the
phenyltelluro thiolate intermediate 10, efficiently achieved in situ
by using allyl bromide, afforded to β-phenyltelluro sulphide 11.
Having synthesised novel organotellurides, where Te···O/S
nonbonded interactions cannot take place, their GPx-like activity
was pursued. We were pleased to find that using compounds 9 and
11 as catalysts under the standard conditions, complete DTT
oxidation was achieved within 4 min and 1 min, respectively. These
findings are in accordance with the presence of Te···O/S nonbonded
interactions, previously reported for selenium-containing GPx
catalysts31, and might indicate a useful criterion for designing new
β-functionalized tellurides highly active as GPx mimics.
respect to the corresponding β-phenyltelluro alcohols 3a,b. Besides
acyclic tellurides, also dithiatellurepane 7 was tested under these
conditions, exhibiting an unexpected low activity in comparison to
what previously observed on cyclic selenides.21,25 The catalytic
activity of various cyclic tellurides is currently under study, in order
to elucidate the behaviour of this class of catalysts with respect to
their acyclic and selenated analogues.
On the basis of these results, having demonstrated the high
catalytic activity of a series of β-functionalised tellurides in the
oxidation of DTT by H2O2, we next turned our attention to evaluate
such activity against different thiols under different conditions.
Benzenethiol was thus used as a substrate and the reduction of
H2O2 was monitored through UV absorption increase at 305 nm,
according to Tomoda’s method. Results of this investigation are
listed in Table 1; kinetic profiles of selected catalysts are depicted in
Figure 4. As can be noticed, in accordance with the study on DTT
oxidation, hydroxy tellurides 1a-c and 2 proved to be the most
active compounds, whereas the presence of a N-tosyl amino group
at the β position (in 4 and 5) resulted in a poor catalyst
performance.
Figure 2: Oxidation of DTTred with H2O2 in the presence of Te-
containing catalysts (1 mol %). Reaction conditions: [DTTred]0=0.14
mM, [H2O2]0=0.14 mM, [catalyst]=0.0014 mM), CD3OD (0.6 mL). In
the control experiment the reaction was run with no catalyst. The
mean ± SD values of three separate experiments are reported.
β-Phenyltelluro- amine 5 and disulfide 6 proved to be the less active
compounds within the studied series. We reasoned that a possible
explanation of this lower activity could be envisaged in the
presence of chalcogen bonds between tellurium and the tosyl or
the disulfide groups (Figure 3) that could hamper the telluride
oxidation or slow the rate of the thiol addition and that of the
reductive elimination reaction of the intermediates involved in the
thiol-peroxidase catalytic pathway.18,28,29 Thus, the observed
decrease of the thiol-peroxidase properties could be related to the
strength of the chalcogen-bonding interactions, originated from the
σ hole in the σ* orbital of the covalent bonds of the tellurium
atom.30
Ph
R
H
Te
N
Tol
p
S
S
S
O
O
Te
Ph
Te
Ph
R
Figure
4 PhSH oxidation GPx assay. Reaction conditions:
5
6
[PhSH]0=1.9 mM, [H2O2]0=8.8 mM, [catalyst]=0.05 mM in methanol
(2 mL) at ambient temperature. The mean ± SD values of three
separate experiments are reported.
Figure 3
In order to test this hypothesis, novel β-phenyltelluro- amine 9 and
Boc
N
Boc
NH
NH2
AcCl/MeOH
3h
NaBH4
Ph2Te2
PhTe
PhTe
PhTe
PhTe
0
1h
°C,
EtOH
0 °C to r.t.
6h
0°C,
8
9
S
R
R
Br
S
NaBH4
TePh
Ph2Te2
PhTe
S
R
0
1h
r.t.
0 °C to
°C,
0
20 min
°C,
11 J. Name., 2018, 00, 1-3 | 3
10
EtOH
3
h
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=
R
CH2OBn
2
Scheme
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Interestingly, according to this assay, the catalytic activity of such the replacement of tellurium with selenium brought about a
View Article Online
DOI: 10.1039/C8NJ00700D
functionalized tellurides was found to be comparable or higher with dramatic decrease in the thiol-peroxidase activity.
respect to literature reported data on tellurium containing
compounds under the same experimental conditions.12
Table 1. Thiol-peroxidase like activity of functionalized
organotellurides according to different methods
Entry
Compound
DTT
PhSH
GSH/NADPH
[a],[d]
[a],[b]
[a],[c]
(T50
<60
<60
<60
)
(T50
)
(T50
<5
<5
<5
<5
)
1
2
3
4
5
6
7
8
9
10
1a
1b
1c
2
235 (±21)
206 (±24)
224 (±32)
68 (±16)
426 (±35)
1007 (±63)
n.d.
90 (±13)
92 (±10)
214 (±34)
600 (±61)
498 (±53)
<60
Figure
5
NADPH-coupled GPx assay. Reaction conditions:
3a
4
9 (±3)
9 (±2)
14 (±3)
n.d.
[NADPH]0=0.3 mM, [GSH]0=1.0 mM, [H2O2]0=2.5 mM, [GR]=4
units/mL, [catalyst]=0.066 mM in pH 7.4 phosphate buffer at
ambient temperature. The mean ± SD values of three separate
experiments are reported.
5
7
780 (±72)
n.d.
9
<5
Table 2. Comparison of the thiol peroxidase activity of β-hydroxy
11
82 (±16)
n.d.
<5
tellurides with their selenium containing analogues
OH
OH
OH
[a] T50 is the time required, in seconds, to reduce the initial thiol concentration with
50% after the addition of H2O2; data in parenthesis are the experimental error. [b] DTT
oxidation was monitored by the mean of 1H NMR spectroscopy; 1 mol % of catalyst
with respect to the thiol was used. [c] Diphenyl disulfide formation was monitored by
UV spectroscopy (305 nm); 2.6 mol % of catalyst with respect to the thiol was used. [d]
NADPH consumption was monitored by UV spectroscopy (340 nm); 6 mol % of catalyst
with respect to GSH was used.
Y
PhY
R
R
R
:
:
:
:
1 Y=Te
12 Y=Se
3 Y=Te
13 Y=Se
b
Y
R
T50
Entry
Catalysta
Te
Te
Te
CH2OBn
CH2OAll
CH2OBn
Me
1
2
3
4
5
1a
1b
3a
<60
<60
In order to verify the activity of such compounds in experimental
conditions closer to the physiological one, we considered to apply
the GSH/GR coupled test27 that better reproduces the cellular
environment. The curves related to the kinetic profile of NADH
consumption for selected compounds are reported in Figure. 5. All
the evaluated Te-containing catalysts behaved as mimics of GPx
under these conditions; β-hydroxy tellurides 1a-c and 2 exhibited
the highest activity, being NADH oxidation complete in 5-10 sec
from the addition of H2O2. In line with the kinetic studies on
dithiothreitol oxidation, a slightly lower activity was found for β-
hydroxy phenyltelluride 3a and β-amino-dialkyl tellurides 4.
Furthermore, significantly higher catalytic activity of the free amino
β-phenyltelluride 9 with respect to the N-Tosyl protected analogue
5 was also found carrying out the GSH/GR coupled test, thus
confirming that the substituent at the β-position is an important
factor that needs to be taken into account for the design of
powerful catalytic antioxidants.
92
88
(±10)
(±15)
(±256)
Te
Se
Se
Se
3b
CH2OBn
12a
3246
2868
CH2OAll
CH2OBn
6
7
12b
13a
(±211)
328
(±34)
(±28)
Se
Me
8
13b
297
a
concentration used for the test: tellurides
selenides
(10 mol%).
Catalysts
(1 mol%),
are
bT50 is measured in
data in
the
experimental
error
seconds;
parenthesis
Conclusions
In this study, the thiol-peroxidase activity of a series of novel
functionalized tellurium containing catalysts has been evaluated
towards different substrates. Although all the synthesised
compounds exhibited remarkable catalytic activity, the results
showed that the nature of the groups close to the tellurium, rather
than the alkyl or aryl substituent directly bound to the Te center,
represents an important factor in order to achieve higher catalytic
Having explored the catalytic activity of differently substituted and
functionalized organotellurides, we synthesised some selenium-
containing anologues19,22a with the aim to evaluate the effect of
these two chalcogen atoms on the catalytic efficiency. Results of
this study on dithiothreitol oxidation are shown in Table 2. As
reported for other classes of chalcogen-containing compounds,1c
4 | J. Name., 2018, 00, 1-3
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efficiency. The thiol peroxidase-like activity of the tested
ARTICLE
(S)-4-Methyl-N-(3-methyl-1-(phenyltellanyl)butan-2-
View Article Online
DOI: 10.1039/C8NJ00700D
organotellurides proved to be much higher with respect to that of yl)benzenesulfonamide (5). NaBH4 (28 mg, 0.75 mmol, 3.0 eq.) was
their selenium-containing analogues. Further studies on the portionwise added to a solution of diphenyl ditelluride (102 mg,
synthesis, the reactivity and the application of tellurium containing 0.25 mmol, 1.0 eq.) in EtOH (2 mL) at 0 °C under inert atmosphere
molecules, as well as the evaluation of their toxicity is currently (N2). After 30 min, a solution of (S)-2-isopropyl-1-tosylaziridine (117
ongoing in our laboratories.
mg, 0.50 mmol, 2.0 eq.) in dry THF (0.5 mL) was slowly added and
the reaction mixture was warmed at RT and stirred for 6 h.
Afterwards, saturated aq. NH4Cl (3 mL) was added and the organic
phase was extracted with Et2O (2 x 5 mL), washed with brine (1 x 3
mL), dried over Na2SO4, filtered and concentrated in vacuo. The
crude material was purified by flash chromatography (petroleum
Experimental
General
1H and 13C NMR spectra were recorded in CDCl3 with a Varian
Mercury Plus instrument or with a Varian INOVA instrument at 400
and 100 MHz, respectively, or with a Varian INOVA instrument at
400 and 100 MHz, respectively. The corresponding residual non-
ether/Et2O
7:1)
to
yield
(S)-4-methyl-N-(3-methyl-1-
(phenyltellanyl)butan-2-yl)benzenesulfonamide 5 (173 mg, 78%). 1H
NMR (400 MHz, CDCl3) δ(ppm): 0.74 (3H, d, J=6.7 Hz), 0.80 (3H, d,
J=6.8 Hz), 1.78-1.90 (1H, m), 2.38 (3H, s, CH3), 2.72 (1H, dd, J=6.5,
12.1 Hz, CHaHbTe), 3.10 (1H, dd, J=4.6, 12.1 Hz, CHaHbTe), 3.18-3.20
(1H, m, CHNH), 4.75 ( 1H, d, J=8.8 Hz, NH), 7.17-7.20 (4H, m), 7.29-
7.33 (1H, m), 7.61-7.63 (4H, m). 13C NMR (100 MHz, CDCl3) δ(ppm):
14.6 (CH2Te), 17.5, 19.2, 32.3, 59.3, 110.9 (TeC), 127.0, 128.0, 129.3,
129.6, 137.8, 138.8, 143.2. MS (ESI positive) m/z (%): 468 [M+Na]+,
(100). Elemental analysis: C18H23NO2STe Calcd. C 48.58%, H 5.21%,
N 3.15%. Found: C 48.49%, H 5.23%, N 3.17%.
1
deuterated solvent was used as a reference (7.26 ppm for H and
77.0 ppm for 13C). 125Te NMR spectra were recorded in CDCl3 at 126
MHz with a Bruker Ultrashield 400 Plus instrument. (PhTe)2 was
used as an external reference (δ = 420 ppm). 1H NMR data are
reported as follows: chemical shift, integration, multiplicity (s =
singlet, bs = broad singlet, d = doublet, t = triplet, m = multiplet, dd
= doublet of doublet, etc.), coupling constant (J) or line separation
(ls), and assignment. Mass spectra (MS) were determined by ESI. All
the reactions were performed under a positive pressure of nitrogen
and were monitored by TLC using commercially available precoated
plates (silica gel 60 F 254) and compounds were visualised by
fluorescence quenching or by staining the plates with acidic p-
anisaldehyde solution. Silica gel 60, 230–400 mesh, was used for
flash column chromatography. Dry solvents were obtained using a
Pure Solv™ Micro system. Commercially available reagents were
used as obtained from freshly opened containers without further
purification. Thiiranes32 and aziridines33 were synthesised according
to literature procedures. Organotellurides 1-7 were achieved from
strained heterocycles following reported procedures (Scheme S1).23
tert-Butyl (S)-(3-methyl-1-(phenyltellanyl)butan-2-yl)carbamate
(8). NaBH4 (28 mg, 0.75 mmol, 3.0 eq.) was portionwise added to a
solution of diphenyl ditelluride (102 mg, 0.25 mmol, 1.0 eq.) in
EtOH (2 mL) at 0 °C under inert atmosphere (N2). After 30 min, a
solution of tert-butyl (S)-2-isopropylaziridine-1-carboxylate (93 mg,
0.50 mmol, 2.0 eq.) in dry THF (0.5 mL) was slowly added and the
reaction mixture was warmed at RT and stirred for 6 h. Afterwards,
saturated aq. NH4Cl (3 mL) was added and the organic phase was
extracted with Et2O (2 x 5 mL), washed with brine (1 x 3 mL), dried
over Na2SO4, filtered and concentrated in vacuo. The crude material
was purified by flash chromatography (petroleum ether/ethyl
acetate
8:1)
to
yield
tert-butyl
(S)-(3-methyl-1-
(phenyltellanyl)butan-2-yl)carbamate 8 (132 mg, 68%). 1H NMR
(400 MHz, CDCl3): δ (ppm) 0.88 (6H, ap t, J = 6.5 Hz), 1.42 (9H, s),
1.71-1.83 (1H, m), 3.06 (1H, dd, J = 4.8, 12.1 Hz, CHaHbTe), 3.13 (1H,
dd, J = 7.2, 12.1 Hz, CHaHbTe), 3.58-3.65 (1H, m, CHNH), 4.56 (1H, d,
J = 9.1 Hz, NH), 7.17-7.21 (2H, m), 7.25-7.28 (1H, m), 7.74-7.77 (2H,
m). 13C NMR (100 MHz, CDCl3): δ (ppm) 15.1 (CH2Te), 18.1, 19.5,
28.4, 33.3, 56.3, 79.2, 111.6, 127.7, 129.2, 138.7, 155.5. 125Te NMR
(126 MHz, CDCl3): δ (ppm) 398.0. MS (ESI positive) m/z (%): 414
[M+Na]+, (100). Elemental analysis: C16H25NO2Te Calcd. C 49.15%, H
6.45%, N 3.58%. Found: C 49.22%, H 6.43%, N 3.56%.
1,4-Bis(phenyltellanyl)butane-2,3-diol (3c). NaBH4 (28 mg, 0.75
mmol, 3.0 eq.) was portionwise added to a solution of diphenyl
ditelluride (102 mg, 0.25 mmol, 1.0 eq.) in EtOH (2 mL) at 0 °C under
inert atmosphere (N2). After 30 min, 2,2'-bioxirane (24 mg, 0.275
mmol, 1.1 eq.) was slowly added and the reaction mixture was
warmed at RT and stirred for 3 h (reaction progress monitored by
TLC). Afterwards, saturated aq. NH4Cl (3 mL) was added and the
organic phase was extracted with Et2O (2 x 5 mL), washed with
brine (1 x 3 mL), dried over Na2SO4, filtered and concentrated in
vacuo. The crude material was purified by flash chromatography
(petroleum
ether/ethyl
acetate
5:1)
to
yield
1,4-
(S)-3-Methyl-1-(phenyltellanyl)butan-2-amine (9). A solution of
acetyl chloride (150 µL, 2.11 mmol, 15 eq.) in MeOH (2 mL) was
bis(phenyltellanyl)butane-2,3-diol 3c (98 mg, 79%). 1H NMR (400
MHz, CDCl3): δ (ppm) 2.96 (2H, bd, J=5.0 Hz, OH), 3.05 (2H, dd,
J=5.0, 12.1 Hz, CHaHbTe), 3.11 (2H, dd, J=7.5, 12.1 Hz, CHaHbTe),
3.75-3.84 (2H, m, CHOH), 7.16-7.20 (4H, m), 7.26-7.30 (2H, m), 7.70-
7.73 (4H, m). 13C NMR (100 MHz, CDCl3): δ (ppm) 15.3 (CH2Te),
73.6, 111.5 (CTe), 127.8, 129.3, 138.4. 125Te NMR (126 MHz, CDCl3):
δ (ppm) 394.1. MS (ESI positive) m/z (%): 520 [M+Na]+, (100).
Elemental analysis: C16H18O2Te2 Calcd. C 38.63%, H 3.65%. Found: C
38.56%, H 3.67%.
slowly added to
a solution of tert-butyl (S)-(3-methyl-1-
(phenyltellanyl)butan-2-yl)carbamate 8 (70 mg, 0.18 mmol, 1.0 eq.)
in MeOH (2 mL) at 0 °C under inert atmosphere (N2). The reaction
mixture was stirred at 0 °C for 6 h and the solvent was removed
under vacuum to afford the crude product. Flash column
chromatography (petroleum ether/ethyl acetate 1:3) gave (S)-3-
methyl-1-(phenyltellanyl)butan-2-amine 9 (46 mg, 88%). 1H NMR
(400 MHz, CDCl3): δ (ppm) 0.91 (6H, ap d, J = 6.8 Hz), 1.61-1.73 (1H,
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m), 2.72-2.76 (1H, m, CHNH), 2.97 (1H, dd, J = 9.3, 11.6 Hz,
CHaHbTe), 3.11 (1H, dd, J = 4.0, 11.6 Hz, CHaHbTe), 7.17-7.21 (2H,
m), 7.24-7.29 (1H, m), 7.71-7.75 (2H, m). 13C NMR (100 MHz, CDCl3):
δ (ppm) 17.9 (CH2Te), 18.1, 19.4, 34.7, 57.7, 112.3, 127.5, 129.1,
138.3. 125Te NMR (126 MHz, CDCl3): δ (ppm) 403.1. MS (ESI positive)
m/z (%): 314 [M+Na]+, (100). Elemental analysis: C11H17NTe Calcd. C
45.42%, H 5.89%, N 4.82%. Found: C 45.47%, H 5.86%, N 4.79%.
Allyl(1-(benzyloxy)-3-(phenyltellanyl)propan-2-yl)sulfane (11).
NaBH4 (28 mg, 0.75 mmol, 3.0 eq.) was portionwise added to a
solution of diphenyl ditelluride (102 mg, 0.25 mmol, 1.0 eq.) in
EtOH (2 mL) at 0 °C under inert atmosphere (N2). After 30 min, 2-
((benzyloxy)methyl)thiirane (99 mg, 0.55 mmol, 2.2 eq.) was slowly
added and the reaction mixture was stirred at 0 °C and the reaction
progress was monitored by TLC. When the starting thiirane had
completely reacted, allyl bromide (54 µL, 0.625 mmol, 2.5 eq.) was
dropwise added and the reaction mixture was stirred at 0°C for 30
minutes and then warmed at RT and stirred for 2 h. Afterwards,
saturated aq. NH4Cl (5 mL) was added and the organic phase was
extracted with Et2O (2 x 5 mL), washed with brine (1 x 5 mL), dried
over Na2SO4, filtered and concentrated in vacuo. The crude material
was purified by flash chromatography (petroleoum ether/diethyl
ether 15:1) to yield allyl(1-(benzyloxy)-3-(phenyltellanyl)propan-2-
yl)sulfane 11 (162 mg, 76%). 1H NMR (400 MHz, CDCl3): δ (ppm)
3.11-3.19 (3H, m, SCH2CH=CH2 and CHS overlapped), 3.24 (1H, dd, J
= 5.4, 11.8 Hz, CHaHbTe), 3.34 (1H, dd, J = 8.0, 11.8 Hz, CHaHbTe),
3.57 (1H, dd, J = 7.0, 9.7 Hz, CHaHbO), 3.72 (1H, dd, J = 4.7, 9.7 Hz,
CHaHbO), 4.46 (2H, ap s, CH2Ph), 4.95-5.01 (2H, m), 5.70-5.82 (1H,
m), 7.14-7.18 (2H, m), 7.23-7.35 (6H, m), 7.72-7.75 (2H, m). 13C
NMR (100 MHz, CDCl3): δ (ppm) 12.9 (CH2Te), 34.5, 45.1, 73.0 73.1,
112.9 (CTe), 117.2, 127.5, 127.57, 127.58, 128.3, 129.1, 134.3,
137.9, 138.3. 125Te NMR (126 MHz, CDCl3): δ (ppm) 456.2. MS (ESI
positive) m/z (%): 449 [M+Na]+, (100). Elemental analysis:
C19H22OSTe Calcd. C 53.56%, H 5.21%. Found: C 53.62%, H 5.19%.
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