Synthesis and characterization of selenium(I/II) and tellurium(IV) derivatives of amino acids

Article abstract of DOI:10.1016/j.jorganchem.2018.08.028

The direct reaction between Te metal and methyl 2-(2-bromoacetamido)propanoate (27) at room temperature, yields the first example of organotellurium(IV) derivative (MeOC(O)CH(Me)NHCOCH₂)₂TeBr₂ (31). Similarly, reaction of Te with methyl 2-(2-bromoacetamido)acetate (26) and methyl 2-(2-bromoacetamido)-3-phenylpropanoate (28) in presence of NaI in acetone gives MeOC(O)CH₂NHCOCH₂I (29), MeOC(O)CH(R)NHCOCH₂)₂TeI₂ (R = H (30) and CH₂Ph (32). Treatment of 26/27/28 with Li₂Te₂/Li₂Se₂ readily provides the [MeOC(O)CH(CH₃)NHCOCH₂]₂Te₂, (33); [MeOC(O)CH₂NHCOCH₂]₂Se₂, (34); [MeOC(O)CH(CH₂Ph)NHCOCH₂]₂Se₂, (35) and [Figure presented] (36). Similarly the reaction of (2,6-dimethyl-4-tert-butylC₆H₂)SeNa with 28 readily provide the [MeOC(O)CH(CH₂Ph)NHCOCH₂]SeC₆H₂-2,6-dimethyl-4-tert-butyl), (37) in good yield. Molecule [MeOC(O)CHNH(Boc)CH₂]₂Se₂, (38) and [NaOC(O)CHNH(Boc)CH₂Te(2,4,6-Me₃C₆H₂] (39) were prepared by the treatment of Li₂Se₂/2,4,6-Me₃C₆H₂TeNa with methyl 3-bromo-2-((tert-butoxycarbonyl)amino)propanoate and N-(t-Boc)-L-serine β-lactone respectively. These compounds are purified by chromatography and characterized by a number of analytical techniques such as (¹H, ¹³C, ⁷⁷Se and ¹²⁵Te NMR) spectroscopy, mass spectrometry and elemental analysis. The single crystal X-ray studies of 29, 30, 31, 36 and 38 revealed the presence of characteristic O?Se/Te, secondary bonding interactions. A detailed analysis of the crystal structures of the compound reveals interesting supramolecular assembly.

Full text of DOI:10.1016/j.jorganchem.2018.08.028

Accepted Manuscript
Synthesis and characterization of selenium(I/II) and tellurium(IV) derivatives of amino
acids
Puspendra Singh, Harkesh B. Singh, Ray J. Butcher
PII:
S0022-328X(18)30332-2
10.1016/j.jorganchem.2018.08.028
JOM 20555
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 9 May 2018
Revised Date: 24 August 2018
Accepted Date: 28 August 2018
Please cite this article as: P. Singh, H.B. Singh, R.J. Butcher, Synthesis and characterization of
selenium(I/II) and tellurium(IV) derivatives of amino acids, Journal of Organometallic Chemistry (2018),
doi: 10.1016/j.jorganchem.2018.08.028.
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Graphical Abstract

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Synthesis and Characterization of Selenium(I/II) and Tellurium(IV)
Derivatives of Amino Acids
Puspendra Singh,a,b Harkesh B. Singh,a* Ray J. Butcherd
[a] Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076,
India
[b] Department of Chemistry, Dr. Shakuntala Misra National Rehabilitation University
Lucknow, Uttar Pradesh, 226017, India
[c] Department of Chemistry, Howard University, WashingtonDC20059, USA
Abstract
The direct reaction between Te metal and methyl 2-(2-bromoacetamido)propanoate (27)
at room temperature, yields the first exapmple of organotellurium(IV) derivative
(MeOC(O)CH(Me)NHCOCH2)2TeBr2 (31). Similarly, reaction of Te with methyl 2-(2-
bromoacetamido)acetate (26) and methyl 2-(2-bromoacetamido)-3-phenylpropanoate (28) in
presence
MeOC(O)CH(R)NHCOCH2)2TeI2 (R = H (30) and CH2Ph (32). Treatment of 26/27/28 with
Li2Te2/Li2Se2 readily provides the [MeOC(O)CH(CH3)NHCOCH2]2Te2, (33);
of
NaI
in
acetone
gives
MeOC(O)CH2NHCOCH2I
(29),
[MeOC(O)CH2NHCOCH2]2Se2, (34); [MeOC(O)CH(CH2Ph)NHCOCH2]2Se2, (35) and
(36). Similarly the reaction of (2,6-dimethyl-4-tert-
butylC6H2)SeNa with 28 readily provide the [MeOC(O)CH(CH2Ph)NHCOCH2]SeC6H2-2,6-
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dimethyl-4-tert-butyl), (37) in good yield. Molecule [MeOC(O)CHNH(Boc)CH2]2Se2, (38) and
[NaOC(O)CHNH(Boc)CH2Te(2,4,6-Me3C6H2] (39) were prepared by the treatment of
Li2Se2/2,4,6-Me3C6H2TeNa with methyl 3-bromo-2-((tert-butoxycarbonyl)amino)propanoate and
N-(t-Boc)-L-serine β-lactone respectively. These compounds are purified by chromatography
13
77
and characterized by a number of analytical techniques such as (1H, C, Se and 125Te NMR)
spectroscopy, mass spectrometry and elemental analysis. The single crystal X-ray studies of 29,
30, 31, 36 and 38 revealed the presence of characteristic O···Se/Te, secondary bonding
interactions. A detailed analysis of the crystal structures of the compound reveals interesting
supramolecular assembly.
Keywords: amino Acids, Selenocysteine, Te(IV) derivatives on amino acid, selenazole,
secondary bonding interactions
1. Introduction
Since discovery of selenocysteine (the 21st amino acid) selenoenzymes, a range of
functions have been assigned [1-3]. The enzymes, which have been extensively studied, are
selenophosphate synthetase, thioredoxin reductase, glutathione peroxidise (GPx), iodothyrone
deiodinase, methionine-R-sulfoxide reductase, formate dehydrogenase, formate hydrogenase,
glycine reductases and proline reductases [2]. The analogous telluroenzyme containing
tellurocysteine, to our knowledge have not been found in living organism. One of the major
problems may be the stability of telluroscysteine which is quite susceptible to β elimination [4].
(Scheme 1) Synthesis of tellurocystine was reported by Silks and co-workers in 1997 [5]. The
chemistry of tellurocysteine containing peptide has been rarely explored due to their inherent
instability.
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Scheme 1 Decomposition of L-tellurocysteine into dehydroalanine
However, some semisynthetic telluroenzymes have been reported and have shown
promising biological activities [6]. Semisynthetic tellurosubtilisin enzyme was prepared
chemically in a three step process through activation of hydroxyl group of Serine-221 of
subtilisin with phenylmethanesulfonylfluoride followed by treatment with NaHTe solution and
finally the resulting telluroprotein was aerially oxidized to enzyme tellurinic acid. The catalytic
ability of tellurosubtilisin was two times more efficient than the selenosubtilisin for GPx activity
[6a]. First telluroproteine was reported by bioincorporation of tellurocysteine into glutathione
transferase. This telluroproteine also exhibit greater GPx activity than the analogous
selenoprotein [6b]. Tellurooxytocin peptide exhibited ~ five times greater binding ability
compared to oxytocin peptide with human oxytocin receptor. Oxytocin and vasopressin are
closely related multifunctional neuropeptides. Upon stimulation into the posterior lobe of
pituitary they are released by enzymatic cleavage for various functions like uterine smooth
muscle contraction during parturition, ejaculation and milk ejection during lactation. So
tellurooxytocin will be a promising drug in future [6c]. More recently some low molecular
weight derivatives of tellurocysteine/tellurocystine (1-6) have been reported and have shown
very good antioxidant activity [7]. (Chart 1) Some related amino acid derivatives of tellurium (7-
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20) have been reported by functionalized amino group of amino acids: L-Valine, L-
Phenylalanine, L-Alanine, L-Leucine and L-Aspartic Acid [8]. The amino acid derivatives of
Te(IV) are rare in particular like trichloro(dioxoethylene-O,O’)-tellurate (21),
hexachlorotellurate (22), (3E)-4-chloro-3- [dichloro(4-methoxyphenyl)tellanyl]-2-methylbut-3-
en-2-ol (23), 1-[butyl(chloro)(L-cysteine)-λ4-tellurinyl]-2-(methoxymethyl)-benzene, (24) and 1-
[butyl(bromo)(L-cysteine)-λ4-tellurinyl]-2-(methoxymethyl)-benzene, (25)
have shown
interesting biological activity [7b,9]. (Chart 1) Compound 21 & 22 specifically inactivates
cysteine proteases by interacting with thiol and ultimately oxidizing the catalytic thiol to a
disulfide. It also inhibits caspase-1 inflammatory products, such as interleukin-18 and
interleukin-1β [7c]. Compound 23 inhibits mainly cathepsin B and therefore is able to induce
apoptosis in HL60 cells with no significant effects observed in normal bone marrow cells. To our
knowledge, there are no report on Te(IV) derivatives on amino acid. In this paper we report our
result on the incorporation of Te(IV) in amino acid and some other related derivatives.
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Chart 1. Representation of tellurocysteine and Te(II & IV) amino acid derivatives.
2. Results and discussion
2.1 Synthesis
The synthesis of tellurium(IV) derivatives of amino acids was approached by insertion of
Te across C-Br/I bond [10]. Oxidative insertion of elemental tellurium into the C–Br bond of 27
at room temperature afforded the (MeOC(O)CH(Me)NHCOCH2)2TeBr2 (31) (Scheme 2). This is
the second report on the insertion of tellurium across C-Br bond [10b]. Reaction of 26, & 28
bromo amides with tellurium took longer time (24–48h) at room temperature and afforded very
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poor yield. For better yield in minimum time we used sodium iodide & 2-3 ml acetone in the
reaction mixture to activate the C–Br bond of chiral bromo amides 26, & 28. These reaction
mixtures afforded the MeOC(O)CH2NHCOCH2I (29), (MeOC(O)CH2NHCOCH2)2TeI2 (30) and
(MeOC(O)CH(CH2PH)NHCOCH2)2TeI2 (32) in good yield at room temperature respectively.
These tellurium(IV) derivatives are highly soluble in common organic solvents like CHCl3,
CH2Cl2, MeOH and DMSO ect. During isolation of 30 from reaction mixture we also obtained
the unreacted yellow colour needle shaped crystal of intermediate, methyl 2-(2-
iodoacetamido)acetate (29) from filterate.
Scheme 2 Synthesis of Te(IV) amino acid derivatives
Some
related
derivatives
[R
(MeOC(O)CH(CH3)NHCOCH2)2Te2
(33),
(MeOC(O)CH(R)NHCOCH2)2Se2,
=
H
(34),
R
=
PhCH2
(35)],
(36)
and
(2,6-dimethyl-4-tert-
butylC6H2)Se[CH2C(O)NHCH(CH2Ph)C(O)OMe] (37) were prepared by the treatment of insitu
prepared THF solution of Li2Te2/Li2Se2/(2,6-dimethyl-4-tert-butylC6H2)SeNa with 26/27/28 in
good yield (Scheme 3). During purification of 35 through column chromatography using silica
gel (60-120) as stationary phase and petroleum ether (60-80 °C)/ethyl acetate (70:30) as the
eluent, 35 is partly oxidized into selenazole (36). The protected selenocysteine 2N-Boc-L-
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selenocystine methyl ester-diselenide, (38) was also prepared for its structural studies by using
reported procedure with methyl 3-bromo-2-((tert-butoxycarbonyl)amino)propanoate and Li2Se2
(Scheme S2, see Supporting Information page S3 and Chart 2) [5]. The related tellurocysteine
derivative [NaOC(O)CH(CH2Te(2,4,6-Me3C6H2)NH(t-Boc)] (39) was prepared by the treatment
of N-(t-Boc)-L-serine β-lactone [8b] with freshly prepared 2,4,6-trimethylbenzenetellurolate
(Scheme S3 see Supporting Information page S4 and Chart 2) The molecular structure of 29, 30,
31, 36 and 38 were determined by single crystal X-ray diffraction studies.
Scheme 3 Synthesis of selenium and tellurium derivatives of amino acids
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Chart 2. Representation of 2N-Boc-L-selenocystine methyl ester-diselenide (38) and related
mesityltellurocysteine derivative (39).
2.2. Spectroscopic Studies
2.2.1. NMR Spectroscopic Studies
1
The molecules were characterized by H, 13C, 77Se and 125Te spectroscopy
methods. The 125Te NMR spectra of 30, 31, 32, 33
568, and 167 ppm respectively. 125Te NMR spectra of all the isolated symmetrical
& 39 exhibited peaks at 589, 814, 595,
diorganotellurium(IV) derivatives (30-32) exhibit a single resonance signal suggesting
their stability in solution state. The 125Te chemical shifts for 39 in CD3OD are upfield
than that of Te(IV) derivatives.
77
The Se NMR spectra of 34, 35, 36, 37 and 38 exhibited peaks at 260, 266, 371,
186 and 295 ppm respectively. These chemical shift values are in the range of Se(I) and
Se(II) derivatives [11]. The 1H NMR spectra of 26
,
29 and 30 showed singlet for CH2Br,
CH2I and CH2Te at 3.93, 3.75 and 3.89 ppm. For the Te(IV) derivatives, CH2Te chemical
shift are very small shift as compared to that of free ligand 26 and 29
.
3.2.2. Solid State Structure Analysis
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Crystal data and structure refinement details for 29
Tables 1. The molecular structure of methyl 2-(2-iodoacetamido)acetate (29), is shown in
Fig. 1 Molecule 29 crystallizes in monoclinic crystal system with C2/c space group. In
, 30, 31, 36 and 38 are given in
.
the solid state, the Iodine atom of the molecule are perpendicular to remain organic
fragment with C1–I bond length 2.1446(25) Å and bond angle C2–C1–I 109.323(149)°.
3.2.3. Molecular Structure of 30, 31, 36 and 38
The molecular structures of 30, 31, 36 and 38 are shown in Fig. 2-5 respectively.
Molecule 30 crystallizes in a monoclinic system with
P21 space group, while 31
crystallizes in triclinic crystal system with P-1 space group. The primary geometry around
the Te atoms of 30 and 31 is distorted trigonal bipyramidal with a strong 1,4-Te···O
secondary bonding interactions (SBIs) in which the more electronegative halo ligands are
situated at the axial positions and the organic ligands occupy equatorial positions. The
lone pair is stereochemically active and distorts the X–Te–X (X = Br and I) and C–Te–C
angles. The tellurium atom in molecule 30 and 31 are covalently bonded with two carbon
atoms at equatorial plane and two halogen atoms (I and Br respectively) are situated at
axial position. Among the 30 and 31, the observed d(Te··O = ~2.90 Å) distances are
longer than Σ rco (Te,O), 2.03 Å, but significantly shorter than Σ rvdw (Te,O), 3.58 Å
v
indicate the presence of attractive intramolecular 1,4-Te···O SBIs [12].
Molecule 36 and 38 crystallizes in monoclinic crystal system with P21/c and C2
space group respectively. The primary geometry around the Se atoms resembles a v-
shaped in which the C1-Se-C3, and C1A-Se1-Se2 and C1B-Se2-Se1 angles are 87.8,
103.1(2) and 102.1(2)° respectively. The crystal packing of 36 displays an interesting
supramolecular synthon. This synthon is based on reciprocal N-H···O H-bonding
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interactions and results in centrosymmetric dimeric units. (Fig. 6c) Among the crystal
lattices of 30, 31 and 38 molecules, C–H···O and N–H···O interactions are thus the only
associative forces that give rise to three dimensional supramolecular motifs via self-
assembly (Fig. 6a, 6b and 6d).
Fig. 1 Molecular structure of 29 showing 50% probability displacement ellipsoids and the
atom numbering scheme.
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Fig. 2 Molecular structure of 30 showing 50% probability displacement ellipsoids and the
atom numbering scheme. Selected bond distances (Å) and angles (°): molecule 1: Te1–C1
2.122(6), Te1–C6 2.140(6), Te1–I1 2.9087(6), Te1–I2 2.8873(6), Te1···O1 2.874(4),
Te1···O4 2.871(4), C1–Te1–C6 92.6(2), I1–Te1–I2 175.73(2). molecule 2: Te2–C11
2.133(5), Te2–C16 2.136(6), Te2–I3 2.9103(6), Te2–I4 2.8810(6), Te2···O7 2.895(4),
Te2···O10 2.961(4), C11–Te2–C16 92.6(2), I3–Te2–I4 174.20(2).
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Fig. 3 Molecular structure of 31 showing 50% probability displacement ellipsoids and the
atom numbering scheme. Selected bond distances (Å) and angles (°): Te–C1A 2.097(10),
Te–C1B 2.125(10), Te–Br1 2.6480(15), Te–Br2 2.6234(14), Te···O1A 2.891(8), Te···O1B
2.898(8), C1A–Te–C1B 96.2(4), Br1–Te–Br2 174.03(6).
Fig. 4 Molecular structure of 36 showing 50% probability displacement ellipsoids and the
atom numbering scheme. Selected bond distances (Å) and angles (°): Se–C1 1.984(2),
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Se–C3 1.944(3), C1–Se–C3 87.84(10), N1–C1–Se 104.43(15), C11–C1–Se 107.07(16),
C4–C1–Se 113.81(16), C2–C3–Se 107.45(16).
Fig. 5 Molecular structure of 38 showing 50% probability displacement ellipsoids and the atom
numbering scheme. Selected bond distances (Å) and angles (°): Se(1)–C(1A) 1.961(6), Se(2)–
C(1B) 1.978(10), C(1A)–Se(1)–Se(2) 103.1(2), C(1B)–Se(2)–Se(1) 102.1(2), Se(1)–Se(2)
2.3100(11), C(2A)–C(1A)–Se(1) 115.3(5).
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(a)
(c)
(d)
(b)
Fig. 6 3-D Supramolecular motif via C─H···O and N─H···O H-Bonds in the lattices of 30 (a),
31 (b) and 38 (d). Only relevant H atoms are shown for clarity. Centrosymmetric pair of 36 (c)
molecules realized by means of a supramolecular synthon provided by amine fragments.
3. Experimental
3.1. Materials and methods
Solvents were dried and distilled by standard procedures. Selenium, Tellurium, Sodium
Iodide, glycine, L-serine, L-alaline, L-phenylalaline, L- tyrosine, thionyl chloride, boc-
anhydride, methyl iodide, superhydride were purchased from sigma aldrich. Methyl ester of
glycine, L-alanine , L-tyrosine , L-phenylalaline [13], Li2Se2 [5], Li2Te2 [5], (o-Me2-C6H2-p-
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tBu)2Se2 [14], (o-Me2-C6H2-p-Me)2Te2 [15] and N-(t-Boc)-L-serine β-lactone [8b] were prepared
according to literature procedure. Functionalized amino acid, methyl 2-(2-
bromoacetamido)acetate (26), methyl 2-(2-bromoacetamido)propanoate (27), and methyl 2-(2-
bromoacetamido)-3-phenylpropanoate (28) were prepared by the reported method (Scheme S1,
see Supporting Information page S3) [13]. Melting points were recorded in capillary tubes and
1
13
77
are uncorrected. The H, C, Se and 125Te NMR spectra were recorded on a Varian VXR 400
spectrometer. Chemical shifts cited were referenced to TMS (1H, 13C) as internal and Me2Se
(77Se) as external standard. The 125Te NMR spectra were recorded on Bruker AMX 400
instruments with dimethyl telluride (Me2Te) as reference. Electron spray mass spectra (ESI-MS)
were performed on a Q-Tof micro (YA-105) mass spectrometer. Mass spectra were obtained
with a Platform II single quadrupole mass spectrometer (Micromass, Altrincham, UK) using a
CH3CN mobile phase. Elemental analyses were performed on a Carlo-Erba model 1106
elemental analyzer. IR spectra were recorded as KBr pellets on a Nicolet Impact 400 and Perkin
FT-IR spectrometer.
3.2. Synthesis of (MeOC(O)CH2NHCOCH2)2TeI2 (30)
To a 50 mL two-necked flask, was taken 26 (1.05 g, 5 mmol) and sodium iodide
(1.00 g, 6.66 mmol) in 3 ml dry acetone. The mixture was stirred for 6 h to obtain a
yellow precipitate. The precipitate obtained was extracted from chloroform to give
colourless crystal of MeOC(O)CH2NHCOCH2I (29), (0.51 g, 40% yield). M.p. 95 °C. 1H
NMR (400 MHz, CDCl3) δ 3.75 (s, CH2I), 3.79 (s, CH3O), 4.07 (d, J = 5.0, CH2), 6.56 (s,
br, NH); Anal. Calcd. for C5H8INO3: C, 23.36; H, 3.14; N, 5.45. Found: C, 23.25; H,
3.44; N, 5.14. The remaining residue was recrystallised from DMSO to afford yellow
needle shaped crystal of 30 (1.20 g, 37% yield). M.p. 175 °C. 1H NMR (DMSO-d6)
δ 3.65
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(s, CH3O), 3.89 (s, CH2Te), 3.91 (d,
41.1, 41.3, 41.4, 51.9, 52.0, 52.1, 167.2, 170.0; 125Te NMR (DMSO-d6)
) calcd for C10H16I2N2O6Te (%) 643.8160; Found 516.90 [M-I]+, FT-
J = 5.7, CH2), 8.93 (t, J
= 5.7, NH); 13C NMR
(DMSO-d6)
δ
δ
589.4. ESI-MS (m/z
IR (KBr) 1633 (CO), 1751 (CO), 3256 (NH) cm-1; Anal. Calcd. for C10H16I2N2O6Te: C,
18.72; H, 2.51; N, 4.37. Found: C, 18.70; H, 2.27; N, 4.65.
3.3. Synthesis of (MeOC(O)CH(Me)NHCOCH2)2TeBr2 (31)
Freshly ground tellurium powder (0.127 g, 1.0 mmol) and 27 (0.50 g, 2.0 mmol) were
stirred together at room temperature for 48 h. The resulting blackish solid was extracted with hot
dichloromethane (4x20 mL) and the extracts were cooled to give crude
(MeOC(O)CH(Me)NHCOCH2)2TeBr2 (31), which was recrystallized from hot CCl4 as colorless
1
needles. Yield: 0.41 g (71%). M.p. 158 °C. H NMR (400 MHz, CDCl3) δ 1.48 (d, J = 4.0 Hz,
2
2
CH3), 3.78 (s, CH3O), 4.45 (dd, J = 12 Hz, CH2Te), 4.56 (dd, J = 12 Hz, CH2Te), 4.64 (m,
CH), 6.92 (m, br, NH); 13C NMR (DMSO-d6) δ 17.2, 46.6, 48.5, 52.1, 165.7, 172.5; 125Te NMR
(CDCl3) 814.1; FT-IR (KBr) 1619 (CO), 1735 (CO), 3336 (NH) cm-1; ESI-MS (m/z) calcd for
C12H20Br2N2O6Te, 575.8750, found: 576.8853 [M+H]+. Anal. Calcd. for C12H20Br2N2O6Te: C,
25.04; H, 3.50; N, 4.87. Found C, 24.87; H, 3.19, N, 4.82.
3.4. Synthesis of (MeOC(O)CH(CH2Ph)NHCOCH2)2TeI2 (32)
Yellow needle shaped crystals of 32 (1.50 g) were prepared from 28 (1.50 g, 5.0
mmol) and an excess of tellurium powder (1.01 g, 8.0 mmol) using the method used
1
above for the preparation of 30. Yield: 30%. M.p. 165 °C. H NMR (CDCl3)
δ 3.28 (m,
CH2), 3.85 (s, CH3), 3.33 (d, 2
J
= 12.6 Hz, CH2), 4.50 (d, 2
J
= 12.6 Hz, CH2), 6.52, (s, br,
31.4, 36.6,
13
NH), 7.19-7.23 (m, 2H-aryl), 7.29-7.38 (m, 3H-aryl); C NMR (CDCl3)
δ
36.7, 52.0, 53.9, 54.3, 126.6, 126.7, 128.3, 129.1, 136.6, 166.5,167.7, 171.3, 171.3; 125Te
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NMR (CDCl3) 595.4. Anal. Calcd. for C24H28I2N2O6Te: C, 35.07; H, 3.43; N, 3.41. Found
C, 35.07; H, 3.31; N, 3.20.
3.5. Synthesis of MeOC(O)CHMeNHCOCH2)2Te2 (33)/MeOC(O)CH2NHCOCH2)2Se2 (34)
Freshly prepared Li2Te2/Li2Se2 (5 mmol) solution in THF was treated with 27
(1.01 g, 4.5 mmol)/ 26 (0.94 g, 4.5 mmol)/ at 0-5 ºC under a brisk flow of nitrogen. The
reaction mixture was stirred at the room temperature for additional 24 h. Then it was
slowly poured into 200 ml of water. The aqueous layer was extracted thrice with ether (3
x 50 ml). The organic layers were combined, dried with sodium sulfate and evaporated to
give yellow oil. This compound was purified by column chromatography using silica gel
as stationary phase and petroleum ether (60-80 °C)/ethyl acetate (70:30) as the eluent.
The yellow solution thus obtained was evaporated to afford a yellow dense liquid of 33
and 34 respectively.
1
Data of 33: (1.50 g, 30% yield); H NMR (CDCl3)
δ
1.45 (d,
J = 7.3 Hz, CH3), 3.75 (s,
CH3O), 4.22 (s, CH2), 4.49 (m, CH), 8.26 (d, 3
J
= 6.8 Hz, br, NH); 125Te NMR (CDCl3)
δ
568.2. ESI-MS (
m/z
) calcd for C12H20N2O6Te2 (%) 547.9446; Found 562.0939 [M+H2O]+
1
Data of 34: (Yield: 1.63 g, 90%). H NMR (CDCl3)
δ
3.40 (s, CH2Se), 3.77 (s, CH3O),
24.91, 41.51, 52.74, 170.83,
) calcd for C10H16N2O6Se2 (%)
13
4.12 (d,
171.55; 77Se NMR (CDCl3)
419.9339; Found 420.9437 [M+H]+.
J = 6.0, CH2), 7.65 (br, NH); C NMR (CDCl3) δ
δ
259.6. ESI-MS (
m
/z
3.6 Synthesis of (MeOC(O)CH(CH2Ph)NHCOCH2)2Se2 (35); and
(36)
The compound 35 was prepared according to the literature reported method [16]
with slight modification affording yellow dense liquid of 35 (Yield: 0.98 g, 67%) along
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with yellow needle shaped crystals of 36 (0.15 g, 10% yield) from 28 (1.50 g, 5.0 mmol)
and freshly prepared solution of Na2Se2 (1.02 g, 5 mmol) in THF. Both compounds were
separated by column chromatography using silica gel as stationary phase and petroleum
ether (60-80 °C)/ethyl acetate (70:30) as the eluent.
Data of 35
: δ 266.4. ESI-MS (m/z) calcd for
77Se NMR (76 MHz, CDCl3)
C24H28N2O6Se2, 600.0278, found: 620.9989 (M+Na).
1
Data for 36: M.p. 120 °C. H NMR (CDCl3)
δ =
3.29 (d, 2J = 14.7 Hz, 1H), 3.42 (d, 2J
14.7 Hz, 1H), 3.57 (d, 2J = 7.7 Hz, 1H), 3.57 (d, 2
br, NH), 7.20-7.22 (m, 2H-aryl), 7.29-7.35 (m, 3H-aryl); 13C NMR (CDCl3)
53.4, 59.5, 127.8, 128.7, 130.4, 134.6, 172.3, 175.5. 77Se NMR (CDCl3)
J = 7.7 Hz, 1H), 3.80 (s, CH3), 6.95 (s,
δ
26.0, 46.7,
δ
371.3. ESI-MS
(m/z) calcd for C12H13NO3Se, 299.0061, found: 322.0086 (M+Na). Anal. Calcd. for
C12H13NO3Se: C, 48.33; H, 4.39; N, 4.70. Found C, 48.45; H, 4.26; N, 4.62.
3.7. Synthesis of (MeOC(O)CH(CH2Ph)NHCOCH2)Se(o-Me2-C6H2-p-tBu) (37)
To a solution of 28 (0.30 g, 1.00 mmol) in 10 ml THF, was added 15 ml solution
of sodium 4-(tert-butyl)-2,6-dimethylbenzeneselenolate (0.26 g, 1.00 mmol) in the same
solvent. The reaction mixture was stirred at room temperature for 12 h and filtered off the
precipitate. The filtrate was concentrated by removing the solvent in vacuo affording a
1
white coloured solid of 37 (0.41, 89% yield). M.p. 118 °C. H NMR (CDCl3)
δ
1.28 (s,
= 5.9,
-aryl), 7.12 (s,
24.83, 29.76, 31.34, 34.51,
9H), 2.52 (s, 6H), 3.02 (dd, J = 2.2, CH2), 3.28 (s, CH2), 3.68 (s, CH3O), 4.78 (q, J
CH), 6.40 (s, br, NH), 6.99 (d,
J = 1.3, 1H-o-aryl), 7.01 (d, J = 2.2, 1H-o
2H-
m
-aryl) 7.22-7.27 (m, 3H-aryl); 13C NMR (CDCl3)
δ
37.97, 52.41, 53.74, 125.24, 127.29, 127.33, 128.74, 129.37, 135.76, 142.84, 152.18,
77
169.33, 171.78. Se NMR (CDCl3) 186.2. ESI-MS:
m/z: calcd for C24H31NO3SeNa (%):
18

ACCEPTED MANUSCRIPT
461.1469, found: 484.1371 (M+Na). Anal. Calcd. for C24H31NO3Se: C, 62.60; H, 6.79; N,
3.04. Found C, 62.39; N, 6.79; H, 3.18.
3.8. Synthesis of [MeOC(O)CHNH(Boc)CH2]2Se2 (38)
This compound was prepared according to the literature method [5] with slight
modification using methyl 3-bromo-2-((tert-butoxycarbonyl)amino)propanoate (0.56 g,
4.0 mmol) and Li2Se2 (0.35 g, 2.0 mmol). The crude product of 38 was recrystallised
from pet-ether (60-80 oC) affording colourless needle shaped crystals of 38. Yield: 0.15 g
(26%). M.p. 85 °C. 1H NMR (CDCl3)
δ
1.45 (s, br, 9H), 3.78 (s, CH3O), 4.62 (m, br, CH),
294.8. ESI-MS ( ) calcd for C18H32N2O8Se2
77
5.42 (m, br, NH); Se NMR (CDCl3)
δ
m/z
(%): 564.0489, found: 587.0388 (M+Na).
3.9. Synthesis of [NaOC(O)CH{CH2Te(2,4,6-Me3C6H2)}NH(Boc)] (39
)
Compound 39 was prepared by following the reported procedure for phenyl
tellurocysteine salt [8b]. For isolation of 39 we used N-(t-Boc)-L-serine β-lactone (0.187, 1.0
mmol) and freshly prepared sodium 2,4,6-trimethylbenzenetellurolate (0.27 g, 1.0 mmol). Yield:
1
0.15 g (26%). M.p. 168-170 °C. H NMR (CD3OD) δ 1.35 (s, 9H), 2.23 (s, 3H), 2.59 (s, 6H),
3
2
3
2
3.03 (dd, J = 6.2, J = 11.3, 1H), 3.13 (dd, J = 5.1, J = 11.3, 1H), 4.21 (m, CH), 6.91 (s, 2H-
aryl); 13C NMR (CD3OD) δ 13.39, 14.92, 21.10, 28.76, 30.19, 58.05, 80.17, 117.72, 128.10,
128.86, 139.59, 146.40, 157.20, 178.03, 140.89; 125Te NMR (CD3OD) δ 166.9. ESI-MS (m/z)
calcd for C17H25NO4TeNa: 437.0846, found: 460.0744 (M+Na).
3.10. X-Ray Crystallographic Study
The single crystal X-ray diffraction measurements were performed on an Oxford
Diffraction 2010 diffractometer. The data were corrected for Lorentz, polarization, and
absorption effects. The structures were determined by routine heavy-atom methods using
19

ACCEPTED MANUSCRIPT
SHELXS 97 [17] and Fourier methods and refined by full-matrix least squares with the
non-hydrogen atoms anisotropic and hydrogen with fixed isotropic thermal parameters of
0.07 Å using the SHELXL 97 [18] program. The hydrogens were partially located from
difference electron density maps, and the rest were fixed at pre determined positions.
Scattering factors were from common sources [19]. Single crystals of 29, 30, 31, 36 and
38 suitable for X-ray crystallography were obtained by slow evaporation of their DMSO
and chloroform solutions. Intensity data were collected on a Bruker PS4 diffractometer
with graphite-monochromated (source: Mo K
α, 0.710 73 Å for 29 & 30 and source: Cu
K
α, 1.541 78 Å for 31 36 and 38) radiation. The O atom of one set of carbonyl in
,
molecule 1/molecule 2 of compound 30 and MeO groups of compounds 31 are disordered
and were refined over two sites with occupancy factors of 0.47(6):0.53(6) for molecule 1
of 30, 0.26(6):0.74(6) for molecule 2 of 30 and 0.51(7):0.49(7) for 31, respectively. The
details of crystal data and structure refinement for 29, 30, 31, 36 and 38 are given in
Table 1. CCDC-1814424 (29), CCDC-1814420 (30), CCDC-1814423 (31), CCDC-
1814422 (36) and CCDC-1814421 (38) contain the supplementary crystallographic data
for this paper.
20

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Table 1. Crystallographic Data and Refinement Details for 29, 30, 31, 36, and 38
Compound
Empirical formula
Formula weight
Wavelength (Å)
Crystal system
Space group
a (Å)
29
30
31
36
38
C5H8INO3 C10H16I2N2O6Te C12H20Br2N2O6Te C12H13NO3Se C18H32N2O8Se2
257.02
0.71073
Monoclinic
C2/c
20.8434(7)
8.6203(5)
9.1894(4)
90
641.65
0.71073
Triclinic
P-1
7.7763(3)
9.1269(5)
25.1820(11)
92.205(4)
93.684(3)
90.236(4)
3952.7(14)
4
575.72
1.54178
Monoclinic
P21
10.1205(18)
4.8494(13)
19.744(7)
90
298.19
1.54184
Monoclinic
P21/c
10.2854(3)
11.2165(3)
10.7735(3)
90
562.38
1.54178
Monoclinic
C2
30.693(2)
5.2953(5)
14.8277(13)
90
b (Å)
c (Å)
α
β
γ
(°)
(°)
(°)
93.354(3)
90
99.17(3)
90
92.451(2)
90
94.896(7)
90
V (Å3)
1648.29(13
8
956.6(5)
2
1.999
1241.75(5)
4
1.595
123(2)
4.30 to 73.43
4.082
2401.1(4)
4
1.556
123(2)
2.89 to 75.46
4.234
Z
D(calcd) (Mg/m3)
T (K)
2.071
2.391
173(2)
3.00 to 28.70
5.157
296(2)
5.12 to 37.61
3.839
123(2)
4.43 to 77.68
17.428
Range of θ(deg)
Abs coeff (mm-1)
Absolute structure parameter
-
-
-0.003(12)
3054
0.06(3)
3965
4137
9220
2466
0.0324
Obsd reflens [I > 2
Final R1 [I > 2 (I)]
wR2 indices [I > 2
σ]
0.0376
0.0717
4137/0/93
1.063
0.0480
0.0538
0.0616
0.1732
3965/1/274
1.102
σ
0.1001
0.1416
0.0823
σ
]
Data/restraints/Parameters
9220/4/395
1.087
3054/1/212
1.052
2466/0/155
1.090
Goodness of fit on F2
21

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4. Conclusions
A new class of stable chiral tellurium(IV) amino acid derivatives is synthesized at room
temperature and structurally characterized. These compounds were prepared by a concise and
flexible synthetic route in excellent yields, which permitted the preparation of a wide range of
compounds. Compound 36 is an interesting byproduct which was confirmed by single crystal X-
ray studies. First time we have reported the tellurium(IV) amino acids derivatives and crystal
structure of protected 2N-Boc-L-selenocystine methyl ester-diselenide. Presence of C-H and N-H
bond in ligand and its derivatives leads to novel supramolecular association involving C-H···O
and N-H···O interactions. Further, protected compounds 30-39 will be used for peptide
synthesis.
Appendix A. Supplementary data
Supplementary
data
associated
with
this
article
can
be
found,
in
the online version, at http://dx.doi.org/xxxxxxxx.
Acknowledgements
H.B.S. is grateful to the Department of Science and Technology (DST), J. C. Bose
Fellowship, New Delhi, for funding. P.S. thanks Science and Engineering Research Board
(SERB), New Delhi for a Start-Up Research Grant for Young Scientist (SB/FT/CS-036/2012).
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Highlights
‹ The synthesis of Te(IV) derivatives of amino acids has been achieved by
insertion of Te across the C-Br/I bond.
‹ The first crystal structure of protected selenocystine, 2N-Boc-L-selenocystine
methyl ester-diselenide.
‹ Synthesis and characterization of selenocyseine and tellurocysteine derivatives
‹ Aerial oxidation of [MeOC(O)CH(CH2Ph)NHCOCH2]2Se2, to a novel
selenazole.