,
2005, 15(2), 67–69
1
mol of KCNO was taken to introduce the α-ureide fragment.
NH2
α,ω-Diureidoacid 1b was obtained by the reaction of (S)-lysine
with 2 mol of KCNO.
Resulting compounds 1a,b were brought into reaction with
equimolar amounts of 4,5-dihydroxyimidazolidin-2-ones 2a,b
under conditions similar to those of diastereospecific reactions
to give compounds 4a,b (Scheme 2). The structures of the
compounds obtained were determined from H and C NMR
data. The signals in the spectra were assigned using highly
O
NH
[
]
HN
n
(S)
O
7
O
OH
H N
2
1
H+
1
13
2
†
1
2
13
H
R
sensitive HMQC and HMBC inversion techniques.
NH2
N
The 1H NMR spectra of the compounds obtained in the
diastereoselective synthesis of glycoluriles by the reaction of
4,5-dihydroxyimidazolidin-2-ones with enantiomers of α-ureido-
O
*
N
HN
O
O
N
n (S)
*
O
2
N
(S)
HN
6
[
]
acids showed doubling of proton signals. Such a doubling is
n
NH
O
O
R
1
not observed in the H NMR spectra of compounds 4. Since the
asymmetric centre in the starting diureidoacids is rather distant
from the ureide fragments involved in the reaction, we can
OH
HN
H N
2
O
6
3
R
H
O
† All new compounds exhibited satisfactory elemental analyses, and
N
*
O
1
13
N
OH
their structures were confirmed by H and C NMR spectroscopy. The
R
(S)
1
13
H and C NMR spectra were recorded on Bruker WM-250 (250 MHz)
N
HO
HO
O
*
N
N
N
n
and Bruker AM-300 (75.5 MHz) spectrometers, respectively. Chemical
NH
NH2
O
shifts were measured with reference to the residual protons of a [2H ]DMSO
O
6
R
solvent (d 2.50 ppm).
R
2
The initial 4,5-dihydroxyimidazolidin-2-ones 2 have been synthesised
7
16
according to a known method from urea and glyoxal.
2
α
N -Carbamoyl-(S)-citrulline 1a: yield 54%, mp 165–168 °C (decomp.),
H NMR ([ H ]DMSO) d: 1.32–1.60 (m, 4H, 2CH ), 2.91–2.97 (m, 2H,
1
2
6
2
H
R
N
CH2), 3.98–4.07 (m, 1H, CH), 5.41 (br. s, 2H, NH2), 5.61 (br. s, 2H,
O
*
3
3
R
N
R
NH ), 6.07 (t, 1H, NH, J 5.5 Hz), 6.29 (d, 1H, NH, J 7.9 Hz), 13.56
2
N
(br. s, 1H, COOH).
N
n (S)
*
O
O
R
*
N
N,N'-Dicarbamoyl-(S)-lysine 1b: yield 54%, mp 174–176 °C
N
1
2
(
decomp.). H NMR ([ H ]DMSO) d: 1.26–1.36 (m, 4H, 2CH ), 1.57
6
2
N
R
*
O
OH
(m, 2H, CH ), 2.97 (m, 2H, CH ), 3.98 (m, 1H, CH), 5.27 (br. s, 4H,
N
2
2
O
H
H
2NH ), 6.53 (br. s, 2H, 2NH), 12.41 (br. s, 1H, COOH).
2
O
N
5
*
O
N
H
(
S)
NH
4
N
7
10
20
N
5
O
H
O
*
HN
8
O
N
R
n
N
N
1
3
14 15
17
O
9
6
n = 1, 2
H
1
N
3
O
2
NH
N
H
16
1
1
12
18
4
19
O
4a
Scheme 1 Possible transformations of α,ω-diureidoacids 1.
2
-{3-[2,5-Dioxoimidazolidin-4(S)-yl]propyl}{(1R,5S+1S,5R)-(2,4,6,8-
the nitrogen atoms in the α- and ω-ureide fragments of these
tetraazabicyclo[3.3.0]octane-3,7-dione)} 4a: yield 54%, mp 223 °C
decomp.). H NMR ([ H ]DMSO) d: 1.38–1.61 (m, 4H, C H , C H ),
compounds by the MNDO method using the MOPAC software
1
2
12
13
(
2
1
1
6
2
2
complex. The data (Figure 1) suggest that the charge dis-
tribution and magnitudes at the nitrogen atoms of the α- and
ω-ureide fragments of 1a are virtually the same and thus none
of the reaction centres is preferable. The same conclusion can
be made from a comparison of calculated data for compounds
1
1
14
.92–3.18 (m, 2H, C H ), 3.98 (br. s, 1H, C H), 5.16–5.24 (br. m, 2H,
2
3
5
4
8
1
C H, C H), 7.26 (br. s, 2H, N H, N H), 7.39 (s, 1H, N H), 7.93 (s, 1H,
15
18
13
1
2
CON H), 10.60 [s, 1H, (CO) N H]. C { H} NMR ([ H ]DMSO) d:
2
6
12
13
11
14
5
2
(
2.8 (C H ), 28.8 (C H ), 39.6 (C H ), 57.3 (C H), 62.4 (C H), 67.7
2 2 2
3
17
7
2
16
C H), 157.6 (C O), 159.4 (C O), 161.3 (C O), 176.2 (C O).
6
a (R = H) and 7a (R = H).
2
3
O
–
0.338
NH2
H
N
20
1
8
11
1
HO
O
H
O
O
Me
H
NH
HN 21
17
NH
N
10
O
2
7
6
O
N
N
19
–
0.405
HN
NH
–0.409
HN
O
15
8
O
N
9
5
N
–0.406
16
22
4
H
O
3
N
O
O
13
14
–
0.336
OH
12
Me
H N
H N
2
2
4b
–
0.335
1
a
6a
6
,8-Dimethyl-2-{4-[2,5-dioxoimidazolidin-4(S)-yl]butyl}{(1R,5S+1S,5R)-
H
O
(2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione)] 4b: yield 47%,
N
O
1
2
HN
OH
mp 236 °C (decomp.). H NMR ([ H6]DMSO) d: 1.31–1.68 (m, 6H,
1
4
15
16
12
11
C H , C H , C H ), 2.65 (s, 3H, C H ), 2.82 (s, 3H, C H ), 3.02–
N
–0.402
2
2
2
3
3
O
13
17
4
3
N
3.37 (m, 2H, C H2), 4.00 (br. s, 1H, C H), 5.10 (d, 1H, C H, J 8.5 Hz),
.19 (d, 1H, C H, J 8.5 Hz), 7.60 (s, 1H, N H), 7.93 (s, 1H, CON H),
0.57 [s, 1H, (CO) N H]. C { H} NMR ([ H ]DMSO) d: 21.7 (C H ),
7.1 (C H ), 27.9 (C H ), 29.7 (C H ), 31.0 (C H ), 41.4 (C H ),
NH
H
2
3
6
18
5
1
2
5
O
–
0.328
NH2
21
13
1
2
15
2
6
2
14
12
11
16
13
2
3
3
2
2
7
a
1
7
4
2
20
3
7.5 (C H), 65.6 (C H), 71.1 (C H), 157.5 (C O), 158.3 (C O), 159.4
7
19
(
C O), 176.1 (C O).
Figure 1 Calculated charges on the atoms of compounds 1a, 6a and 7a
MNDO).
2-Amino-5-[(1R,5S+1S,5R)-(3,7-dioxo-2,4,6,8-tetraazabicyclo[3.3.0]-
(
oct-2-yl)]-2(S)-pentanoic acid 8: yield 57%, mp 290–293 °C (decomp.).
H NMR ([ H ]DMSO) d: 1.31–1.80 (m, 3CH ), 2.81–3.06 (m, CH),
.17–5.27 (m, 2H, 2CH), 7.29 (s, 1H, NH), 7.32 (s, 1H, NH), 7.54 (s,
H, NH). C { H} NMR (CD OD) d: 22.5 (CH ), 27.3 (CH ), 40.2
CH ), 54.0 (CHNH ), 63.2 (CH), 69.1 (CH), 161.2 (CO), 163.2 (CO),
74.00 (COOH).
1
2
6
2
α,ω-Diureidoacids 1a,b were synthesised by the reaction
5
1
(
of commercially available (S)-citrulline and (S)-lysine with
1
3
1
KCNO by analogy with reported procedures.10 The molecule of
3
2
2
2
2
(
S)-citrulline already contains an ω-ureide fragment; therefore,
1
6
8
Mendeleev Commun. 2005