SYNTHESIS OF DEUTERATED OR TRITIATED GLYCINE
267
Table 2. Compounds present in the reaction mixture after
heating of Gly and GlyOCH3 deposited on 5% Pd/C in a H2
gas atmosphere (400 hPa, 180°C, 10 min) according to mass
spectrometry data
The tritiation was conducted by placing 17 mg of
5% Pd/C with Gly (10 : 1) into a tube and evacuating
the tube down to 0.1 hPa. Tritium gas was injected up
to a pressure of 400 hPa. The reaction was carried out
at 180°C for 10 min. After removal of tritium gas, the
products were washed on the filter with aqueous
methanol (three times, 1 mL each) to remove the cat-
alyst. Labile tritium was removed by evaporation of
solvents. Labeled glycine was purified by HPLC on a
Reprosil pur Diol column (10 × 150 mm size, 5 μm
particle size) in the acetonitrile–10 mM NH4H2PO4
solvent system (75 : 25) at a 2 mL/min flow rate. The
retention times were as follows (min): Gly, 9.51; Gly-
OCH3, 7.95; sarcosine, 8.55. The yield of labeled gly-
cine was 50% and the specific radioactivity was 27–
31 Ci/mmol. Labeled GlyOCH3 obtained under simi-
lar conditions had a specific radioactivity of 18–
20 Ci/mmol.
Thus, the simultaneous formation of labeled CH3–
NH–CH2COOH (sarcosine) with a specific radioac-
tivity of 45–50 Ci/mmol can be considered as an addi-
tional result of the study. Sarcosine is known to be
investigated for treatment of the prostate cancer and to
be used as a nootropic agent against mental depression
and schizophrenia symptoms. The presence of the
labeled sarcosine analogue will be beneficial for fur-
ther investigation.
Molecular peaks
Reaction product
[M + H] [M – H]
Products formed from glycine
Gly
76
90
74
88
CH3–NH–CH2COOH
NH2–CH2CONHCH2COOH
HOOC–CH2–NH–CH2COOH
CH3–NH–CH2COOCH3
133
134
104
131
132
–
Products formed from methyl glycinate
GlyOCH3
90
76
90
–
74
88
–
Gly
CH3–NH–CH2COOH
CH3–NH–CH2COOCH3
104
CH3OOC–CH2–NH–CH2COOCH3 162
116
–
–
O
HN
O
O
It is worth noting that deuteration of Gly gave a
ACKNOWLEDGMENTS
compound differing from GlyOCH3, but with the
same molecular weight (Table 2). The methyl group
was attached to the amino rather than carboxy group.
This was indirectly evidenced by the fact that this
methyl group was not removed upon the conventional
alkaline hydrolysis. Furthermore, this compound dif-
fered from O-methylated Gly in the chromatographic
mobility and was identified as N-methylglycine (sar-
cosine). Analysis was carried out on a Reprosil pur
DIOL column (Dr. Maisch GmbH, Germany, 4 ×
150 mm size, 3 μm particle size) in the acetonitrile—
10 mM NH4H2PO4 solvent system (75 : 25) at a
1 mL/min flow rate.
This work was partially supported by the Russian
Science Foundation (project no. 16–14–00077) and
Programs of the Presidium of the RAS “Fundamental
Research for the Development of Biomedical Tech-
nologies” and “Molecular and Cell Biology and Post-
Genomic Technologies.”
REFERENCES
1. Shevchenko, V.P., Nagaev, I.Yu., Alfeeva, L.Yu.,
Andreeva, L.A., Shevchenko, K.V., and Myasoe-
dov, N.F., Radiokhimiya, 2004, vol. 46, no. 1, pp. 63–
71.
This conclusion is not at variance with our earlier
data [4, 5]. The tritiation of polyamides (5% Pd/C,
190°C, 15 min) was accompanied by active deamina-
tion. For example, ethylenediamine was converted to
secondary amines under these conditions. Hence, Gly
may be converted to HOOC–CH2–NH–CH2COOH
and further (upon decarboxylation) to CH3–NH–
CH2COOH with the molecular weight equal to that of
GlyOCH3 (Table 2).
2. V'yunova, T.V., Andreeva, L.A., Shevchenko, K.V.,
Shevchenko, V.P., Bobrov, M.Yu., Bezuglov, V.V., and
Myasoedov, N.F., Dokl. Akad. Nauk, 2008, vol. 419,
no. 1, pp. 136–137.
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Myasoedov, N.F., Radiokhimiya, 2010, vol. 52, no. 3,
pp. 277–280.
4. Shevchenko, V.P., Nagaev, I.Yu., and Myasoedov, N.F.,
Mechennye tritiem lipofil’nye soedineniya (Tritium-
Labeled Lipophilic Comppounds), Moscow: Nauka,
2003.
5. Shevchenko, V.P., Nagaev, I.Yu., Potapova, A.V., and
Myasoedov, N.F., Radiokhimiya, 1994, vol. 36, no. 5,
pp. 440–444.
This may account for the appearance of isoto-
pomers of methylated Gly containing 4 (31%) and 5
(28%) deuterium atoms in the mass spectra of the deu-
terated reaction mixtures obtained from Gly. Mean-
while, much less deuterium atoms are incorporated in
the molecule upon the deuteration of GlyOCH3.
Translated by Z. Svitanko
DOKLADY CHEMISTRY Vol. 483 Part 1 2018