Paper
Organic & Biomolecular Chemistry
1
3
C NMR (DMSO-d
6
): 160.59 (s, C-2), 159.76 (s, C-6), 154.25 sion of the starting 6 was reached (monitored by TLC). Then
(s, C-4), 140.01 (s, C-8), 113.44 (s, C-5), 99.43 (s, C-2′), 62.20 (s, the solvent was evaporated and the residue was dissolved in
CH
2
(Et)), 53.02 (s, OCH
3
), 45.09 (s, C-1′), 15.05 (s, CH
3
(Et)).
acetonitrile, and 365 mg (2 mmol) of 5 was added. The reac-
UV, λmax = 250.1 nm, 279.5 nm.
tion mixture was stirred for 2 h and then concentrated
9
-Adenylacetaldehyde (7a). Diethyl acetal derivative 6a in vacuo. The residue was applied on a silica gel column (20 ×
(500 mg, 1.75 mmol) was dissolved in 0.3 M HCl in water. The 150 mm), and eluted with a gradient of methanol (0% → 10%)
reaction mixture was placed at +37 °C for 8–10 h until the total in chloroform. The fraction containing the target products was
conversion of the starting 6 was reached (monitored by TLC). concentrated as white amorphous powder in 575 mg (87%)
Then the solvent was evaporated and the product was concen- yield.
1
3
trated as white neutral-coloured powder in 350 mg (99%) yield.
H NMR (CD
3
OD): 7.72 (1H, t, J2′, 1′ 4.8 Hz, CH-2′(anti-)),
1
3
H NMR (DMSO-d ): 9.69 (1H, s, CH-2′), 8.16 (1H, s, H-2), 8.10 7.66 (1H, s, H-8 (anti-)), 7.60 (1H, s, H-8 (syn-)), 7.08 (1H, t, J
6
2′,
3
(
1H, s, H-8), 7.17 (2H, s, NH
2
), 5.20 (2H, br.s, CH
2
-1′).
1′ 4.0 Hz, CH-2′ (syn-)), 6.48 (2H, br.s, 2-NH
C NMR (DMSO-d ): 196.79 (s, C-2′), 155.75 (s, C-6), 152.44 4.3 Hz, CH
s, C-2), 149.62 (s, C-4), 141.20 (s, C-8), 118.44 (s, C-5), 52.19 (s, 4.51 (2H, d, J
2
), 4.86 (2H, d, J1′, 2′
1
3
3
6
2
-1′ (syn-)), 4.76 (2H, d, J2′, 1′ 4.8 Hz, CH -1′(anti-)),
2
2
2
(
7.2 Hz, CH –P (syn-)), 4.42 (2H, d, J
CH , P
2
CH , P
2
2
C-1′).
7.0 Hz, CH
2
–P (anti-)), 4.10–4.03 (8H, m, CH
2
(Et) (syn + anti)),
1
5
3
N NMR (DMSO-d
6
): 233.82 (N-1), 228.61 (N-3), 157.60 3.27 (6H, 2 × s, OCH
3
(syn- + anti-)), 1.26 (6H, t, JCH , CH 7.1
3
2
3
(N-7), 149.01 (N-9), 80.75 (6-NH2).
Hz, CH (Et) (syn-)), 1.19 (6H, t,
J
7.1 Hz, CH (Et)
3
CH3, CH2 3
UV, λmax = 266.0 nm.
(anti-)).
1
3
9
-{2-[(Phosphonomethyl)oximino]ethyl}adenine diethyl ester
8a). To a solution of 350 mg of 7a (1.75 mmol) in acetonitrile 153.67 (2 × s, C-4), 151.31 & 151.15 (2 × s, C-2), 149.21 (s, C-2′
20 mg (1.75 mmol) of 5 was added. The reaction mixture was (syn-)), 147.87 (s, C-2′ (anti-)), 137.81 & 137.75 (2 × s, C-8),
6
C NMR (DMSO-d ): 156.81 & 156.78 (2 × s, C-6), 153.76 &
(
3
1
stirred for 2 h and then concentrated in vacuo. The residue was 116.45 & 116.30 (2 × s, C-5), 69.68 (d, JC, P 159.0 Hz, CH
chromatographed on silica gel, target fractions were concen- (syn-)), 67.09 (d, J
trated to result in 510 mg of pure 8a (85% yield). Syn- and anti- 6.1 Hz, CH
2
–P
1
2
158.9 Hz, CH –P (anti-)), 61.98 (d, J
(Et, syn-)), 61.81 (d, JC, P 6.1 Hz, CH
C, P
2
C, P
2
2
2
(Et, anti-)),
isomers were isolated from one another by HPLC.
56.02 (s, OCH
(anti-)), 38.92 (s, C-1′ (syn-)), 16.25 (d, J
3
(anti-)), 53.53 (s, OCH
3
3
(syn-)), 40.96 (s, C-1′
Syn-isomer:
5.5 Hz, CH (Et,
C, P
3
1
3
H NMR (DMSO-d
6
): 8.16 (1H, s, H-2), 8.14 (1H, s, H-8), 7.21 syn-)), 16.16 (d, JC, P 5.5 Hz, CH
3
(Et, anti-)).
): 22.17 (s), 22.24 (s).
HRMS: calcd for C H N O P 372.1311 [M + H ], found
3
3
31
(
2H, br.s, NH
.1 Hz, CH -1′), 4.54 (2H, d, J
C, P 8.3 Hz, JCH , CH3 7.1 Hz, 2 × CH
2
), 7.16 (1H, t, J2′, 1′ 4.1 Hz, CH-2′), 5.06 (2H, d, J1′, 2′
P NMR (DMSO-d
6
2
+
4
7.1 Hz, CH –P), 4.10 (4H, dq,
2
CH , P 2
13 21 6 5
2
3
3
3
J
2
(Et)), 1.27 (6H, t, JCH , CH
372.1315.
UV, λmax = 252.2 nm.
9-{2-[(Phosphonomethyl)oximino]ethyl}guanine
2
3
2
7
.1 Hz, CH
3
(Et)).
1
3
C NMR (DMSO-d ): 155.93 (s, C-6), 152.56 (s, C-2), 149.54
diethyl
6
(
(
s, C-2′), 148.88 (s, C-4), 140.74 (s, C-8), 118.53 (s, C-5), 67.70 ester (8c). Diethyl acetal derivative 6b (100 mg, 0.4 mmol) was
1
2
d, JC, P 159.4 Hz, CH
2
–P), 61.95 (d, JC, P 6.1 Hz, CH
2
(Et)), dissolved in 1 M HCl in water. The reaction mixture was
3
2
3
7
8.93 (C-1′), 16.24 (d, J
5.5 Hz, CH (Et)).
placed at +37 °C for 8–10 h until the total conversion of the
starting 6 was reached (monitored by TLC). Then the
C, P
3
3
1
P NMR (DMSO-d
6
): 22.09 (s).
+
HRMS: calcd for C12
42.1206.
H
19
N
6
O
4
P 342.1206 [M + H ], found solvent was evaporated and the residue was dissolved in
acetonitrile, and 75 mg (0.4 mmol) of 5 was added. The reac-
Anti-isomer:
tion mixture was stirred for 2 h and then concentrated
1
6
H NMR (DMSO-d ): 8.15 (1H, s, H-2), 8.12 (1H, s, H-8), in vacuo. The residue was applied on a silica gel column (20 ×
3
.78 (1H, t, J2′, 1′ 4.8 Hz, CH-2′), 7.22 (2H, br.s, NH ), 4.97 150 mm), and eluted with a gradient of methanol (0% → 20%)
2
3
2
(2H, d,
J1′, 2′ 4.8 Hz, CH
2 CH2, P
-1′), 4.35 (2H, d, J 7.0 Hz, in chloroform. The fraction containing the target products was
3
CH
2
–P), 3.97 (4H, m, CH (Et)), 1.18 (6H, t, JCH , CH 7.1 Hz, concentrated as white amorphous powder in 104 mg (82%)
2
3
2
CH (Et)).
yield.
3
1
3
1
C NMR (DMSO-d
6
): 155.82 (s, C-6), 152.42 (s, C-2), 149.40
6
H NMR (DMSO-d ): 7.74 (1H, s, H-8 (syn-)), 7.72 (1H, s, H-8
3
(
s, C-2′) 147.81 (s, C-4), 140.71 (s, C-8), 118.40 (s, C-5), 67.07 (d, (anti-)), 7.69 (1H, t,
J
2′, 1′ 4.7 Hz, CH-2′ (anti-)), 7.03 (1H, t,
1
2
3
3
JC, P 158.6 Hz, CH –P), 61.73 (d, J
6.1 Hz, CH (Et)), 41.15
J2′, 1′ 4.3 Hz, CH-2′ (syn-)), 4.99 (2H, d, J
4.3 Hz, CH -1′
1′, 2′ 2
2
C, P
2
3
3
(s, C-1′), 16.13 (d, JC, P 5.5 Hz, CH
3
(Et)).
2
(syn-)), 4.85 (1H, d, J2′, 1′ 4.7 Hz, CH -1′ (anti-)), 4.56 (2H, d,
3
1
2
2
P NMR (DMSO-d
6
): 22.26 (s).
J
CH , P 6.9 Hz, CH
2
–P (syn-)), 4.42 (2H, d, JCH , P 6.6 Hz, CH
HRMS: calcd for C H N O P 342.1206 [M + H ], found (anti-)), 4.23–4.06 (8H, m, CH (Et)), 1.36 (6H, t, J
2
–P
7.1 Hz,
2
2
+
3
1
2
19
6
4
2
CH , CH
3
2
3
3
42.1206.
UV, λmax = 260.2 nm.
-{2-[(Phosphonomethyl)oximino]ethyl}-2-amino-6-methoxy- C-2), 153.18 & 153.07 (2 × s, C-4), 149.24 (s, C-2′ (syn-)), 148.29
purine diethyl ester (8b). Diethyl acetal derivative 6b (500 mg, (s, C-2′, (anti-)), 139.45 & 139.41 (2 × s, C-8), 117.41 & 117.29
CH
3
(Et, syn-)), 1.29 (6H, t, JCH , CH 7.1 Hz, CH
3
(Et, anti-)).
3
2
1
3
C NMR (DMSO-d
6
): 159.23 (s, C-6), 155.40 & 155.36 (2 × s,
9
1
1
.98 mmol) was dissolved in 0.3 M HCl in water. The reaction (2 × s, C-5), 68.90 (d, JC, P 162.8 Hz, CH
2
–P (syn-)), 68.42 (d,
1
2
mixture was placed at +37 °C for 8–10 h until the total conver-
JC, P 162.1 Hz, CH –P (anti-)), 64.16 (d, J
6.5 Hz, CH (Et,
2
C, P
2
Org. Biomol. Chem.
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