7440
L. Y. Wu et al. / Bioorg. Med. Chem. 15 (2007) 7434–7443
4.7. N-Benzoyl-N-methylserine-[PO K-NH-Glu(OK)-
OK]-OK (1b) (derived from 7b using general procedure B)
C H N O P: C, 65.64; H, 5.97; N, 4.25. Found: C,
36 39 2 8
65.58; H, 5.67; N, 4.31.
2
1
Yield 85%. H NMR (300 MHz, D O; two rotamers,
major/minor = 1.7:1): d 1.80–1.89 (m, 2H), 2.14–2.23
4.11. 2-{[2-(Benzoyl-methyl-amino)-ethoxy]-hydroxy-
phosphorylamino}-pentanedioic acid tripotassium salt (1d)
(derived from 7d using general procedure B)
2
(
m, 2H), 3.00 (s, 1H), 3.05 (s, 2H), 3.46–3.49 (m, 1H),
3
2
.97–4.11 (m, 2H), 4.14–4.33 (m, 1H), 4.47–4.52 (m,
H), 5.00–5.05 (m, 1H), 7.44–7.54 (m, 5H). C NMR
1
3
1
Yield 82%. H NMR (300 MHz, D O, two rotamers,
2
(
75 MHz, D O; two rotamers): d 30.00 and 30.06,
major/minor = 1.1:1): d 1.80–1.92 (m, 2H), 2.13–2.24
(m, 2H), 3.06 (s, 1.4H), 3.14 (s, 1.6H), 3.44–3.57 (m,
2H), 3.76–3.84 (m, 2H), 4.03 (q, 2H, J = 5.7 Hz), 7.44–
2
3
5
6
1
1
1
2.31 and 33.98, 34.07 and 35.66, 35.72, 56.79 and
6.89 and 57.04, 61.03 and 61.13, 61.86, 62.24, 65.03,
5.10 and 65.19, 126.93 and 127.02, 128.94 and 129.09,
30.32 and 130.38, 135.27, 135.66, 161.32, 174.64,
74.73, 174.96, 175.59, 181.42 and 181.48, 181.66 and
1
3
7.53 (m, 5H). C NMR (75 MHz, D O two rotamers):
2
d 31.82 and 31.85, 33.28 and 33.55 and 33.66, 38.82,
48.18 and 48.29, 51.50 and 51.61, 56.41 and 56.56,
61.33 and 61.40 and 61.70 and 61.77, 126.43 and
126.45, 128.55 and 128.64, 129.79 and 129.97, 134.96
and 135.11, 173.84 and 174.72, 181.18 and 181.28,
3
1
81.71, 183.21. P NMR (121 MHz, D O; two rota-
2
+
mers): d 7.36 and 7.58 FAB-HRMS (M+K) Calcd
6
22.8806. Found: 622.8837 for C H K N O P.
16 17 5 2 10
3
1
1
and 7.72 (externally referenced with O-phosphoric acid).
82.81 and 182.86. P NMR (121 MHz, D O): d 7.43
2
4
.8. 2-[(2-Benzoylamino-ethoxy)-benzyloxy-phosphoryl-
ꢀ
amino]-pentanedioic acid dibenzyl ester (7c) (using general
procedure A)
FAB-HRMS (MꢀH)
Calcd 500.9634. Found:
500.9631 for C H K N O P.
8
1
5
17
3
2
1
Yield: 25%. H NMR (300 MHz, CDCl ): d 1.93–2.02
4.12. N-Benzoyl-D-Ser-[PO Bn-NH-Glu(OBn)-OBn]-
2
3
(
m, 2H), 2.36–2.44 (m, 2H), 3.63–3.70 (m, 3H), 4.10–
OBn (7e) (using general procedure A)
4
7
2
6
1
1
.13 (m, 3H), 4.94–5.09 (m, 6H), 7.25–7.88 (m, 20H),
1
3
1
Yield 57%. H NMR (300 MHz, CDCl , two rotomers):
.85–7.88 (d, 2H). C NMR (75 MHz, CDCl ): d
3
3
9.86, 30.38, 30.45, 41.21, 54.36, 54.53, 66.14, 66.76,
8.00, 69.13, 69.19, 77.70, 127.82, 129.21, 129.96,
34.72, 136.23, 136.30, 136.45, 136.65, 167.96, 168.02,
d 1.80–2.05 (m, 2H), 2.24–2.41 (m, 2H), 4.22–4.38 (m,
1H), 4.80–4.95 (m, 2H), 5.01–5.14 (m, 8H), 5.07–5.10
(m, 1H), 7.20–7.40 (m, 24H), 7.74 (d, J = 7.02 Hz,
3
1
13
73.11, 173.12, 173.17. P NMR (121 MHz, CDCl ):
3
2H), 7.82 (d, J = 6.28 Hz, 1H). C NMR (75 MHz,
CDCl ): d 29.65, 30.48, 53.65, 55.27, 63.27, 66.26,
66.78, 67.46, 68.53, 68.59, 127.17, 128.21, 128.35,
+
d 9.55. FAB-HRMS (M+H) Calcd 645.2366. Found:
6
3
45.2337 for C H N O P.
3
5
38
2
8
128.43, 128.52, 128.56, 128.68, 131.76, 131.82, 133.56,
135.13, 135.48, 135.62, 135.82, 167.58, 170.50, 172.32,
4
.9. 2-[(2-Benzoylamino-ethoxy)-hydroxy-phosphoryl-
3
172.83. P NMR (121 MHz, CDCl , two rotomers
1
amino]-pentanedioic acid tripotassium salt (1c) (derived
from 7c using general procedure B)
3
and two diastereomers): d 5.79 and 6.30 (externally
referenced with O-phosphoric acid). HRMS (FAB+)
Calcd [M+1] = 779.2733. Found: [M+1] = 779.2728 for
C H N O P.
1
Yield 75%. H NMR (300 MHz, D 0): d 1.77 (q, 2H,
2
J = 7.42 Hz), 2.09 (t, 2H, J = 8.15 Hz), 3.38 (dt, 2H,
J = 8.79 Hz), 3.49 (t, 1H, J = 5.12 Hz), 3.83 (dt, 2H,
4
3
43
2
10
1
3
J = 5.88 Hz), 7.41–7.70 (m, 5H). C NMR (75 MHz,
4.13. N-Benzoyl-D-Ser-[PO K-NH-Glu(OK)-OK]-OK
2
D 0): d 31.55, 31.63, 33.46, 40.65, 40.75, 56.60, 62.74,
2
(1e) (derived from 7e using general procedure B)
6
1
2.81, 127.05, 128.62, 131.96, 133.45, 170.93, 181.40,
3
1
1
81.46, 182.51. P NMR (121 MHz, D 0): d 8.54.
Yield 55%. H NMR (300 MHz, D O): d 1.27 (t,
2
2
ꢀ
FAB-HRMS (MꢀK)
Calcd 448.9918. Found:
J = 7.31 Hz, 6H), 1.95–2.20 (m, 2H), 2.42 (t, J = 6.58,
2H), 3.07 (q, J = 7.21 Hz, 4H), 3.57–3.65 (m, 1H),
4
48.9916 for C H K N O P.
14 16 2 2 8
3
.99–4.11 (m, 2H), 4.42–4.46 (m, 1H), 7.43–7.65 (m,
7H), 7.83 (d, J = 7.16 Hz, 2H). C NMR (75 MHz,
1
3
4.10. 2-{[2-(Benzoyl-methyl-amino)-ethoxy]-benzyloxy-
phosphorylamino}-pentanedioic acid dibenzyl ester (7d)
D O): d 10.37, 24.01, 28.99, 42.08, 52.93, 55.35, 55.86,
2
(
using general procedure A)
60.77, 63.75, 127.20, 128.63, 132.39, 132.66, 170.94,
1
3
1
72.19, 174.05, 174.29. P NMR (121 MHz, D O): d
2
1
Yield 31%. H NMR (300 MHz, CDCl ). Note: while
5.24 (externally referenced with O-phosphoric acid).
HRMS (FAB+) Calcd [M+1] = 570.9091, found
[M+1] = 570.9087 for C H O N PK .
3
1
isolated as a homogeneous species, H NMR character-
ization of this compound was complicated due to exten-
sive broadening caused by N-rotomerism in the presence
1
5
15 10
2
4
1
of P-diastereomers. C NMR (75 MHz, CDCl two
3
4.14. 2-Hydroxymethyl-4-phenyl-butyric acid benzyl
ester (4f)
3
rotamers and two diastereomers): d 29.72, 29.79, 30.39,
3
6
1
1
8.97, 48.26, 48.32, 64.40, 66.77, 67.66, 68.53, 68.58,
8.64, 127.42, 128.17, 128.22, 128.63, 128.78, 128.87,
29.00, 129.05, 129.86, 136.05, 136.60, 137.06, 172.02,
Anhydrous THF (20 mL) was cooled to ꢀ78 ꢁC and
treated with LDA (1 M/THF) (12.8 mL, 12.8 mmol).
The solution was stirred at ꢀ78 ꢁC and then a solution
of 4-phenyl-butyric acid (1.0 g, 6.09 mmol, 0.48 equiv)
in THF (3 mL) was added dropwise over 1 min. The
3
1
72.79, 173.13, 173.19. P NMR (121 MHz, CDCl ):
3
+
d 8.30 and 8.38 FAB-HRMS (M+H) Calcd 659.2522.
Found: 659.2549 for C H N O P. Anal. Calcd for
3
6
40
2
8