3978
L. Liu et al. / Bioorg. Med. Chem. 10 (2002) 3973–3979
chromatography (10–30% MeOH/CHCl3). 1H NMR
(CDCl3, 300 MHz) 8.30 (1H, s), 7.40 (9H, m), 5.30 (2H,
s), 4.70 (m, 1H), 4.40 (2H, m), 3.45 (2H, s), 1.80–3.10
(12H, m), 1.30 (3H, s). CI MS 477 (M+1).
131, 129, 127, 69, 42. MS FAB+ (glycerol): 254
(M+1), 277 (M+23).
1-Methyl-2-phenyl-serine (13). This compound, as a
mixture of diasteromers, was synthesized from ethyl
benzoylacetate, which was mono-alkylated with methyl
iodide (86% yield), and then brominated with bromine
(quantitative). The bromide was replaced by azide (97%
yield), and the azide was reduced with triphenylphos-
phine to amine (75% yield). The ketone group in the
compound was then reduced with sodium borohydride
(quantitative), and the final product was obtained from
hydrolysis with stoichiometric sodium hydroxide
(quantitative). This product was purified with reverse
phase chromatography and obtained as a white solid.
1H NMR (D2O) 7.25 (5H, m), 4.85–5.00 (1H, ss), 1.10–
1.60 (3H, ss). MS FAB+ (glycerol): 218 (M+23). MS
FABꢄ(glycerol): 194 (Mꢄ1).
[3-Benzyloxy-5-(4-dimethylaminomethyl-phenylsulfanyl)-
5,6,7,8-tetrahydro-quinoline-4-yl]methanol (9a). 29 mg of
8a was dissolved in 2 mL of dry ether. 10 of mg of
LiAlH4 was then added at 0 ꢁC. The reaction mixture
was stirred under argon at room temperature for 50
min, which was quenched by addition of 2 mL of ethyl
acetate. The mixture was extracted with 10 mL of ethyl
acetate twice, and the extracts were concentrated in vacuo.
The product was purified by silica flash chromatography
(10–50% MeOH/CHCl3). 1H NMR (CDCl3) 8.30 (1H, s),
7.40 (9H, m), 5.22 (2H, d), 5.00 (2H, m), 4.70 (1H, m), 3.45
(2H, s), 1.80–3.10 (12H, m). CI MS 435 (M+1).
3-Benzyloxy-5-(4-dimethylaminomethyl-phenylsulfanyl)-
5,6,7,8-tetrahydro-quinoline-4-carbaldehyde (10a). 0.1
mL of pyridine was dissolved in 2 mL of dry methylene
chloride and 60 mg CrO3 was added to the solution. The
resulting slurry was stirred for 60 min at room tem-
perature. This slurry was then treated with 43 mg of 9a
dissolved in 2 mL of CH2Cl2. The reaction mixture was
stirred for 15 min, after which the slurry was passed
through a small column of Celite. No further purifica-
tion was conducted on this compound as it decomposes
quickly in air. CI MS: 433 (M+1).
References and Notes
1. (a) John, R. A. Biochim. Biophys. Acta 1995, 1248, 81. (b)
Hayashi, H. J. Biochem. 1995, 118, 463. (c) Schneider, G.;
Kack, H.; Lindqvist, Y. Structure 1998, 8, R1.
2. Martell, A. E. Acc. Chem. Res. 1989, 22, 115.
3. Metzler, D. E.; Snell, E. E. J. Am. Chem. Soc. 1952, 74,
979.
4. Of course pyridoxamine can then react with an a-keto acid
to regenerate pyridoxal via transamination. However, in aqu-
eous solution excessive amounts of keto acid must be added in
order to achieve transamination with simple free pyridox-
amine. No keto acids were added in our studies reported here.
5. (a) Breslow, R.; Hammond, M.; Lauer, M. J. Am. Chem.
Soc. 1980, 102, 421. (b) Zimmerman, S. C.; Czarnik, A. W.;
Breslow, R. J. Am. Chem. Soc. 1983, 105, 1694. (c) Breslow,
R.; Czarnik, A. W.; Lauer, M.; Leppkes, R.; Winkler, J.;
Zimmerman, S. J. Am. Chem. Soc. 1986, 108, 1969. (d) Bre-
slow, R.; Chmielewski, J.; Foley, D.; Johnson, B.; Kumabe,
N.; Varney, M.; Mehra, R. Tetrahedron 1988, 44, 5515. (f)
Breslow, R.; Canary, J. W.; Varney, M.; Waddell, S. T.; Yang,
D. J. Am. Chem. Soc. 1990, 112, 5212. (g) Fasella, E.; Dong,
S. D.; Breslow, R. Bioorg. Med. Chem. 1999, 7, 709.
6. (a) Kikuchi, J.-I.; Zhang, Z.-Y.; Murakami, Y. J. Am.
Chem. Soc. 1995, 117, 5383. (b) Kuang, H.; Distefano, M. D.
J. Am. Chem. Soc. 1998, 120, 1072. (c) Shogren-Knaak, M. A.;
Imperiali, B. Bioorg. Med. Chem. 1998, 7, 1993.
5-(4-dimethylaminomethyl-phenylsulfanyl)-3-hydroxy-
5,6,7,8-tetrahydro-quinoline-4-carbaldehyde (2). 20 mg of
10a was dissolved in 4 mL of 18% HCl aqueous solu-
tion. The reaction was refluxed at 150 ꢁC under argon
for 1.5 h. The reaction mixture was then cooled to room
temperature, neutralized with NaHCO3 aqueous solu-
tion, and extracted with ethyl acetate twice. The extracts
were concentrated in vacuo, and the remaining oil was
purified by silica flash chromatography (10–50%
1
MeOH/CHCl3). The final product is a yellow solid. H
NMR (CD3CN): 10.40 (1H, s), 7.95 (1H, s), 7.46 (2H, d,
J=8.1 Hz), 7.28 (2H, d, J=8.1 Hz), 4.65 (1H, m), 3.38
(2H, s), 2.60 (3H, m), 2.18 (6H, s), 1.78 (3H, m). CI MS:
343 (M+1).
7. Liu, L.; Breslow, R. Tetrahedron Lett. 2001, 42, 2775.
8. Zimmerman, S. C.; Breslow, R. J. Am. Chem. Soc. 1984,
106, 1490.
9. Matsushima, Y.; Martell, A. E. J. Am. Chem. Soc. 1967, 89,
1331.
10. Kalyankar, G. D.; Snell, E. E. Biochemistry 1962, 1, 594.
11. Koh, J. PhD thesis, Department of Chemistry. Columbia
University, 1994.
12. (a) Thanassi, J. W. Biochemistry 1970, 9, 525. (a) Tha-
nassi, J. W. Biochemistry 1971, 11, 2909. (a) Thanassi, J. W.
Biochemistry 1973, 12, 5109.
13. The detailed reaction conditions: pH 9.0, 60.0 ꢁC,
0.0015 M in a-benzyl aminomalonic acid 11, 0.0003 M in pyr-
idoxal or its analogue, 0.0003 M in CuCl2, and 0.02 M in
CHES buffer (ethanol/water=7/3). We conducted the dec-
arboxylation reaction under basic conditions, under acidic
conditions the reaction intermediate undergoes C-40 protona-
tion, affording pyridoxamine and keto acid as products. For
details, see Zabinski, R. F.; Toney, M. D. J. Am. Chem. Soc.
2001, 123, 193.
(3). With a similar route, we obtained 3 as a yellow
1
solid. H NMR (CD3CN) 10.60 (1H, s), 8.32 (1H, s),
4.75 (1H, m), 3.05–1.30 (27H, m). CI MS: 349 (M+1).
(5). Similarly to 2 and 3, 5 was obtained as a yellowish
1
brown solid. H NMR (CD3CN): 10.53 (1H, s), 8.32
(1H, s), 7.40 (5H, m), 4.71 (1H, m), 2.70–1.65 (6H, m).
CI MS: 286 (M+1).
Benzyl aminomalonic acid (11). This compound was
synthesized from diethyl aminomalonate, which was
protected with BOC anhydride (94% yield), alkylated
with benzyl bromide (92% yield), deprotected with tri-
fluoroacetic acid (quantitative), and finally hydrolyzed
with stoichiometric sodium hydroxide (quantitative).
The product was purified with reverse phase chromato-
1
graphy and obtained as a white solid. H NMR (D2O):
7.30 (5H, m), 3.15 (2H, s). 13C NMR (D2O): 180, 138,