616
G.-J. Wang et al. / European Journal of Medicinal Chemistry 39 (2004) 611–617
5.1.3.1. L-Arginine methyl ester (E-1). E-1·HCl: Yield 71%.
4.15 (m, 3H). 13C-NMR (151 MHz, D2O) d (ppm) 13.9, 22.4,
24.3, 25.5, 27.4, 28.1, 28.4, 31.5, 40.7, 52.9, 67.9, 157.1,
170.5. MS (FAB) m/e (M+ + H) 273.2. HRMS (FAB) calc.
for C13H29N4O2 (M+ + H) 273.2291, found 273.2296.
21
D
1
␣
͓ ͔
+16.9° (c 1.01, H2O). H-NMR (600 MHz, D2O) d
(ppm) 1.68–1.79 (m, 2H), 1.97–2.05 (m, 2H), 3.26 (t,
J = 6.8 Hz, 2H), 3.86 (s, 3H), 4.21 (t, J = 6.5 Hz, 1H).
13C-NMR (151 MHz, D2O) d (ppm) 24.2, 27.3, 40.7, 52.9,
54.1, 157.2, 170.8. MS (FAB) m/e (M+ + H) 189.1. HRMS
(FAB) calc. for C7H17N4O2 (M+ + H) 189.1352, found
189.1362.
5.1.3.8. L-Arginine octyl ester (E-8). E-8·HCl: Yield 35%.
21
D
1
␣
͓ ͔
+6.0° (c 0.72, H2O). H-NMR (600 MHz, D2O) d
(ppm) 0.83 (t, J = 7.0 Hz, 3H), 1.16–1.37 (m, 10H), 1.62–
1.81 (m, 4H), 1.92–2.51 (m, 2H), 3.23 ( t, J = 6.9 Hz, 2H),
4.16–4.29 (m, 3H). 13C-NMR (151 MHz, D2O) d (ppm) 13.9,
14.6, 22.5, 24.3, 25.5, 27.5, 28.1, 28.7, 31.5, 40.8, 53.0, 68.0,
157.2, 170.5. MS (FAB) m/e (M+ + H) 287.2. HRMS (FAB)
calc. for C14H31N4O2 (M+ + H) 287.2447, found 287.2441.
5.1.3.2. L-Arginine ethyl ester (E-2). E-2·HCl: Yield 72%.
21
D
1
␣
͓ ͔
+10.3° (c 0.58, H2O). H-NMR (600 MHz, D2O) d
(ppm) 1.30 (t, J = 7.2 Hz, 3H), 1.68–1.76 (m, 2H), 1.98–2.03
(m, 2H), 3.25 (t, J = 6.9 Hz, 2H), 4.17 (t, J = 6.4 Hz, 1H), 4.31
(m, 2H). 13C-NMR (151 MHz, D2O) d (ppm) 13.1, 23.7,
26.8, 40.2, 52.4, 63.6, 156.7, 169.8. MS (FAB) m/e (M+ + H)
203.3. HRMS (FAB) calc. for C8H19N4O2 (M+ + H)
203.1508, found 203.1514.
5.1.3.9. L-Arginine nonyl ester (E-9). E-9·HCl: Yield 37%.
21
D
1
␣
͓ ͔
+6.3° (c 0.42, H2O). H-NMR (600 MHz, D2O) d
(ppm) 0.83 (t, J = 7.0 Hz, 3H), 1.21–1.37 (m, 12H), 1.69–
1.77 (m, 4H), 1.96–2.01 (m, 2H), 3.24 (t, J = 6.8 Hz, 2H),
4.17–4.31 (m, 3H). 13C-NMR (151 MHz, D2O) d (ppm) 14.0,
14.6, 22.6, 24.2, 25.5, 27.6, 28.0, 28.7, 28.8, 31.5, 40.8, 53.0,
68.0, 157.2, 170.5. MS (FAB) m/e (M+ + H) 301.1. HRMS
(FAB) calc. for C15H33N4O2 (M+ + H) 301.2604, found
301.2607.
5.1.3.3. L-Arginine propyl ester (E-3). E-3·HCl: Yield 72%.
21
D
1
␣
͓ ͔
+9.9° (c 0.76, H2O). H-NMR (600 MHz, D2O) d
(ppm) 0.94 (t, J = 7.4 Hz, 3H), 1.68–1.80 (m, 4H), 2.03 (m,
2H), 3.27 (m, 2H), 4.19–4.26 (m, 3H). 13C-NMR (151 MHz,
D2O) d (ppm) 10.1, 21.7, 24.3, 27.4, 40.7, 53.0, 69.5, 157.2,
170.5. MS (FAB) m/e (M+ + H) 217.1. HRMS (FAB) calc.
for C9H21N4O2 (M+ + H) 217.1665, found 217.1658.
5.1.3.10. L-Arginine decyl ester (E-10). E-10·HCl: Yield
21
38%. ␣ –2.7° (c 0.28, H2O). 1H-NMR (600 MHz, D2O)
͓ ͔
d (ppm) 0.D80 (t, J = 6.9 Hz, 3H), 1.40–2.02 (m, 20H), 3.20 (t,
J = 6.8 Hz, 2H), 4.15-4.30 (m, 3H). 13C-NMR (151 MHz,
D2O) d (ppm) 14.0, 14.4, 22.6, 24.2, 25.5, 27.6, 28.1, 28.7,
28.8, 31.5, 40.8, 53.2, 68.1, 157.0, 170.5. MS (FAB) m/e (M+
+ H) 315.2. HRMS (FAB) calc. for C16H35N4O2 (M+ + H)
315.2760, found 315.2762.
5.1.3.4. L-Arginine butyl ester (E-4). E-4·HCl: Yield 68%.
21
D
1
␣
͓ ͔
+6.6° (c 0.90, H2O). H-NMR (600 MHz, D2O) d
(ppm) 0.89 (t, J = 7.4 Hz, 3H), 1.37 (m, 2H), 1.67 (m, 2H),
1.77 (m, 2H), 3.01 (m, 2H), 3.26 (m, 2H), 4.19 (t, J = 6.3 Hz,
1H), 4.26–4.31 (m, 2H). 13C-NMR (151 MHz, D2O) d (ppm)
13.3, 18.9, 24.3, 27.4, 30.1, 40.7, 53.0, 67.7, 157.1, 170.4.
MS (FAB) m/e (M+ + H) 231.1. HRMS (FAB) calc. for
C10H23N4O2 (M+ + H) 231.1821, found 231.1829.
5.1.3.11. L-Arginine benzyl ester (E-B). E-B·HCl: Yield
21
58%.
␣
͓ ͔
–0.40° (c 0.52, H2O). 1H-NMR 13C-NMR
(600 MHz,DD2O) d (ppm) 1.95 (m, 4H), 3.20 (t, J = 6.9 Hz,
2H), 4.17 (t, J = 6.3 Hz, 1H), 5.20–5.34 (dd, J = 71.9,
11.9 Hz, 2H), 7.41 (m, 5H). 13C-NMR (151 MHz, D2O) d
(ppm) 24.1, 27.3, 40.5, 52.8, 70.0, 129.1, 129.2, 129.4,
135.0, 157.0, 170.0. MS (FAB) m/e (M+ + H) 265.1. HRMS
(FAB) calc. for C13H21N4O2 (M+ + H) 265.1665, found
265.1666.
5.1.3.5. L-Arginine pentyl ester (E-5). E-5·HCl: Yield 71%.
21
D
1
␣
͓ ͔
+7.3° (c 0.60, H2O). H-NMR (600 MHz, D2O) d
(ppm) 0.89 (t, J = 7.1 Hz, 3H), 1.35 (m, 4H), 1.69–1.80 (m,
4H), 2.03 (m, 2H), 3.28 (t, J = 6.8 Hz, 2H), 4.20 (t, J = 6.3 Hz,
1H), 4.26–4.33 (m, 2H). 13C-NMR (151 MHz, D2O) d (ppm)
13.7, 22.0, 24.3, 27.4, 27.5, 27.8, 40.7, 53.0, 68.0, 157.2,
170.5. MS (FAB) m/e (M+ + H) 245.1. HRMS (FAB) calc.
for C11H25N4O2 (M+ + H) 245.1978, found 245.1968.
Acknowledgements
5.1.3.6. L-Arginine hexyl ester (E-6). E-6·HCl: Yield 68%.
21
D
1
␣
͓ ͔
+7.9° (c 0.75, H2O). H-NMR (600 MHz, D2O) d
The authors would like to thank the National Science
Council of the Republic of China for financially supporting
this research under Contract No. NSC 90-2113-M-259-017
to C.P.C. and NSC 92-2320-B-077-010 to G.J.W.
(ppm) 0.87 (t, J = 4.9 Hz, 3H), 1.30–1.38 (m, 6H), 1.69–1.85
(m, 4H), 2.03 (m, 2H), 3.27 (t, J = 6.9 Hz, 2H), 4.20 (t,
J = 6.4 Hz, 1H), 4.26–4.33 (m, 2H). 13C-NMR (151 MHz,
D2O) d (ppm) 13.8, 22.3, 24.3, 25.2, 27.5, 28.0, 31.0, 40.8,
53.0, 68.0, 157.2, 170.5. MS (FAB) m/e (M+ + H) 259.2.
HRMS (FAB) calc. for C12H27N4O2 (M+ + H) 259.2134,
found 259.2136.
References
[1] J.F. Kerwin Jr, J.R. Lancaster Jr, P.F. Feldman, J. Med. Chem. 38
(1995) 4343–4362.
[2] D.J. Stuehr, N.S. Kwon, C.F. Nathan, O.W. Griffith, P.L. Feldman,
J. Wiseman, J. Biol. Chem. 266 (1991) 6259–6263.
5.1.3.7. L-Arginine heptyl ester (E-7). E-7·HCl: Yield 37%.
21
D
1
␣
͓ ͔
+6.6° (c 0.66, H2O). H-NMR (600 MHz, D2O) d
(ppm) 0.69 (t, J = 6.2 Hz, 3H), 1.11–1.20 (m, 8H), 1.52–1.61
(m, 4H), 1.84–1.87 (m, 2H), 3.10 (t, J = 6.8 Hz, 2H), 4.07–
[3] O.W. Griffith, D.J. Stuehr, Annu. Rev. Physiol. 57 (1995) 707–736.
[4] R.G. Knowles, S. Moncada, Biochem. J. 298 (1994) 249–258.