4316
H. Lu et al. / Tetrahedron Letters 42 (2001) 4313–4316
N-[hydroxy(n-butyl)phosphinothioyl]-
3. Reisenauer, A. M.; Krumdieck, C. L.; Hlasted, C. H.
L
-glutamic acid tri-
lithium salt (1a). 1H NMR (CD3OD): l 0.80 (t, J=7.2
Hz, 3H), 1.25 (m, 2H), 1.40–1.59 (m, 2H), 1.61–1.73 (m,
2H), 1.74–1.92 (m, 2H), 2.08–2.27 (m, 2H), 3.58 (dt,
J=10.8 Hz, J=6.3 Hz, 1H); 13C NMR (CD3OD): l
12.96, 23.87 (d, J=18.70 Hz), 26.43, 32.74, 34.12, 37.54
(d, J=93.98 Hz), 56.98, 180.91 (d, J=3.38 Hz), 181.99;
FABHRMS (M−Li) calcd 294.0729. Found 294.0728 for
C9H15Li2NO5PS.
Science 1977, 198, 196.
4. (a) Goldman, P.; Levy, C. C. Proc. Natl. Acad. Sci. 1967,
58, 1299; (b) Levy, C. C.; Goldman, P. J. Biol. Chem.
1967, 242, 2933; (c) McCullough, J. L.; Chabner, B. A.;
Bertino, J. R. J. Biol. Chem. 1971, 246, 7207; (d) Sher-
wood, R. F.; Melton, R. G.; Alwan, S. M.; Hughes, P.
Eur. J. Biochem. 1985, 148, 447.
5. Kahn, T. H.; Eno-Amooquaye, E. A.; Searle, F.; Browne,
P. J.; Osborn, H. M. I.; Burke, P. J. J. Med. Chem. 1999,
42, 951.
6. Rodriguez, C. E.; Lu, H.; Dinh, T. T.; Mlodnosky, K. L.;
Dastgah, A.; Lam, V. Q.; Nichols, C. B.; Berkman, C. E.
Bioorg. Med. Chem. Lett. 1999, 9, 1415.
7. (a) Bell, C. F. In Principles and Applications of Metal
Chelation; Atkins, P. W.; Holker, J. S. E.; Holliday, A.
K., Eds.; Oxford University: Oxford, 1977; (b) Prasad, A.
S. In Biochemistry of Zinc; Frieden, E., Ed.; Plenum:
New York, 1993.
8. Myers, R. S.; Paton, P. T.; Dastgah, A.; Martell, J. R.;
Berkman, C. E. Anal. Biochem. 1999, 275, 187.
9. (a) Watanabe, Y.; Nakatomi, M. Tetrahedron Lett. 1998,
39, 1583; (b) Seeberger, P. H.; Yau, E.; Caruthers, M. H.
J. Am. Chem. Soc. 1995, 117, 1472.
10. Experimental procedures for compounds 3 and 4. A
solution of 9-fluorenemethanol (0.53 g, 2.7 mmol) and
DEA (0.52 ml, 3.0 mmol) in benzene (6.0 ml) was added
via syringe to a stirring solution of alkylphosphonic
dichloride (0.42 ml, 3.0 mmol) and 1H-tetrazole (0.02 g,
0.27 mmol) in benzene (10 ml) under an argon atmo-
sphere at 4°C. The resulting solution was warmed to
room temperature and stirred for 3 h, followed by the
N-[hydroxy(n-butyl)phosphinothioyl]-L-glutamic acid tri-
lithium salt (1b). 1H NMR (CD3OD): l 0.85 (t, J=7.5
Hz, 3H), 1.31 (m, 2H), 1.51–1.76 (dm, 4H), 1.80–1.96 (m,
2H), 2.13–2.31 (m, 2H), 3.64 (dt, J=11.1 Hz, J=6.0 Hz,
1H); 13C NMR (CD3OD): l 14.43, 25.10 (d, J=18.45
Hz), 27.91, 34.22 (d, J=3.75 Hz), 35.64, 39.44 (d, J=
119.18 Hz), 58.40, 182.38 (d, J=4.65 Hz), 183.32;
FABHRMS (M−Li) calcd 294.0729. Found 294.0705 for
C9H15Li2NO5PS.
N-[hydroxy(n-butyl)phosphinothioyl]-L-glutamic acid tri-
lithium salt (2a). 1H NMR (CD3OD): l 1.57–1.77 (m,
2H), 1.88–2.14 (dm, 2H), 3.27 (dt, J=6.3 Hz, J=5.7 Hz,
1H), 6.98–7.08 (m, 3H), 7.57–7.64 (dm, 2H); 13C NMR
(CD3OD): l 34.19, 35.35, 58.50, 128.54, 128.71, 130.20,
131.80, 131.94, 144.51 (d, J=128.6 Hz), 181.62 (d, J=
5.10 Hz), 183.69; FABHRMS (M−Li) calcd 314.0416.
Found 314.0433 for C11H11Li2NO5PS.
N-[hydroxy(n-butyl)phosphinothioyl]-L-glutamic acid tri-
lithium salt (2b). 1H NMR (CD3OD): l 1.45–1.58 (m,
2H), 1.81–1.83 (m, 2H), 3.28 (dt, J=6.0 Hz, J=2.8 Hz,
1H), 6.96–7.02 (m, 3H), 7.57–7.64 (dm, 2H); 13C NMR
(CD3OD): l 33.72 (d, J=4.65 Hz), 35.55, 58.55, 128.45,
128.62, 130.24, 131.92, 132.04, 144.40 (d, J=131.4 Hz),
182.18 (d, J=3.75 Hz), 183.27. FABHRMS (M−Li) calcd
314.0416. Found 314.0411 for C11H11Li2NO5PS.
addition of a solution of L-glutamic acid dimethyl ester
(0.57 g, 3.2 mmol) and DEA (0.59 ml, 3.4 mmol) in
benzene (6.0 ml). The solution was stirred for another 3 h
and then filtered and concentrated in vacuo to afford a
yellow oil, which was purified by flash chromatography
(EtOAc:hexane 2:1, v/v) to give the ester 3 (62%) and 4
(60%). Phosphonamidates 3 and 4 were fractionally
recrystallized from acetone and hexane to afford the
individual diastereoisomers, respectively.
14. Experimental procedures for compounds 7 and 8. Reflux-
ing a solution of 5, 9 or 10 (0.45 mmol) and quinine (146
mg, 0.45 mmol) in methanol (5 ml) for 24 h followed by
concentration in vacuo gave a yellow oil, which was
recrystallized from acetone and hexane (3:10 v/v) to give
compounds 7 from 5 or 9 and 8 from 10.
15. Experimental procedures for compounds 9 and 10. Into a
flask charged with 1H-tetrazole (0.02 g, 0.3 mmol) and
alkylphosphonic dichloride (3.3 mmol) in benzene (10.0
mL) were added sequentially ethanedithiol monoacetate
(0.41 g, 3.0 mmol) and a solution of diisopropylethyl-
amine (0.52 mL, 3.0 mmol) in benzene (5.0 mL) via
syringe at 4°C under an argon atmosphere. The solution
was allowed to warm to room temperature and stirred
until ethanedithiol monoacetate was consumed (approxi-
mately 3 h) as monitored by TLC. Glutamic acid
dimethyl ester (0.58 g, 3.3 mmol) and DEA (0.59 mL, 3.4
mmol) in benzene (5.0 mL) was added dropwise to the
reaction mixture and allowed to stir for an additional 3 h.
The reaction mixture was concentrated in vacuo and
purified by flash chromatography to give 9 (65%) and 10
(60%) [EtOAc:hexane 4:1 v/v (9a: Rf=0.35. 9b: Rf=0.25.
10a: Rf=0.36. 10b: Rf=0.27)].
11. Jackson, J. A.; Berkman, C. E.; Thompson, C. M. Tetra-
hedron Lett. 1992, 33, 6061.
12. Experimental procedures for compounds 5 and 6. Reflux-
ing a solution of 3 or 4 (0.66 mmol) and Lawesson’s
reagent (0.37 mmol) in toluene (16 ml) for about 2 h
followed by concentration in vacuo gave a yellow oil,
which was purified by flash chromatography to give 5
(89%) and 6 (84%) [CH2Cl2: EtOAc 50:1 v/v (5a: Rf=
0.43. 5b: Rf=0.42. 6a: Rf=0.46. 6b: Rf=0.44)].
13. General experimental procedures for compounds 1 and 2.
Phosphonamidothionates 7 and 6 or 8 (0.1 mmol) were
dissolved in methanol (0.6 mL), into which was added a
1.0 M aqueous solution of LiOH (0.36 mL). The solution
was stirred at room temperature for 15 h and then
filtered. The solvent was evaporated in vacuo to give 1
and 2 as white residue, which was further purified by
re-suspension in anhydrous methanol and filtration (0.2
mm Teflon membrane) to provide the desired pure
trilithium salts 1 (68%) and 2 (81%).
16. Wiesler, W. T.; Caruthers, M. H. J. Org. Chem. 1996, 61,
4272.
.