CONVENIENT SYNTHESES OF PHOSPHINIC ANALOGUES
675
30 min, evaporated to one-half in vacuo and then dryness in vacuo and the residue was coevaporated
diluted with dry dioxane to the initial volume, giv- with H2O (15 mL) in vacuo. To the final residue 20%
ing solution (S).
HCl (60 mL) was added, refluxed under argon atmo-
sphere for 3 h and extracted with Et2O (2 × 15 mL).
The aqueous layer was evaporated to dryness in vacuo,
the residue was dissolved in H2O (20 mL) and purified
To 11.5 g (53 mmol) of diethyl acetamidomalonate
in dry dioxane (80 mL) 2.0 М EtONa/EtOH (3 mL)
was added that gave white amorphous gel-like solu-
tion, which was evaporated to one-third in vacuo and
then diluted with dry dioxane to the initial volume. To
this, solution (S) was added and the reaction mixture
became slightly cloudy after stirring at 20°С for 35 h
under Argon atmosphere. Reaction mixture was evap-
orated to dryness in vacuo, 20% HCl (200 mL) was
added to the residue, refluxed under argon atmo-
sphere for 3 h, evaporated to dryness in vacuo and
coevaporated in vacuo with H2O (3 × 30 mL). This latter
residue was dissolved in 15% i-PrOH (50 mL) and puri-
fied on a Dowex 50Wx8 (H+-form) resin (V = 300 mL) by
eluting with 15% i-PrOH. Fractions containing Glu-
γ-PH (IV) were combined, evaporated to dryness
in vacuo, crystallized from H2O/EtOH and dried
in vacuo over P2O5 to give (II) (5.86 g, 66%), contam-
on Dowex 50Wx8 (H+-form) resin (V = 35 mL) by
eluting first with H2O and then with 0.5 M HCl to iso-
late pure GABA-PH. Fractions containing GABA-PH
hydrochloride were combined, evaporated to dryness
in vacuo, the residue was dissolved in minimal volume
of EtOH and propylene oxide added dropwise until
precipitation started. The mixture was allowed to
stand at +4°С until complete precipitation, the solid
was filtered off, recrystallized from H2O/EtOH and
dried in vacuo over P2O5 to give (VI) (0.53 g, 60%), mp
208–211°С (lit.: 209–213°С [22]), Rf 0.42 (А). 1H NMR
(D2O) δ: 6.89 (dt, 1 H, JHP 510.7, JHH 1.5, P-H), 3.00
(t, 1 H, JHH 7.4, CH2NH2), 1.85–1.74 (m, 2 H,
CH2CH2NH2), 1.59–1.49 (m, 2 H, CH2P). 13C NMR
(D2O) δ: 42.83 d (JCP 17.5), 30.99 d (JCP 89.8), 22.15 s.
31P NMR (D2O) δ: 28.57.
inated with less than 4% (according to 31P-NMR) of
2-amino-4-phosphonobutyric acid. Analytical sam-
ple (after additional purification on Dowex 50Wx8
resin, elution with 15% i-PrOH and subsequent
H2O/EtOH crystallization): mp 216–218°С, dec. (lit.:
193–197°С, dec. [18]; 208–210°С, dec. [20]; 221–
ACKNOWLEDGMENTS
This work was supported by the Russian Founda-
tion of Basic Research (Grant no. 16-04-01523),
Academy of Finland (Agreement no. 292574), the
strategic funding from University of Eastern Finland.
MAK is gratefully acknowledging the support of the
D. Zimin Dynasty Foundation.
1
222°С, dec. (L-isomer) [15]), Rf 0.24 (А). H NMR
(D2O) δ: 6.98 (dt, 1 H, JHP 523, JHH 1.5, P-H), 4.09 (t,
1 H, JHH 6.1, CH), 2.22–2.07 (m, 2 H, CH2P), 1.83–
13
1.61 (m, 2 H, CH2CH). C NMR (D2O) δ: 174.91 s,
56.39 d (JCP 16.1), 29.48 d (JCP 88.9), 25.35 s.
31P NMR (D2O) δ: 29.67.
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RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 42 No. 6 2016