S. Kuttab et al. / Bioorg. Med. Chem. 9 (2001) 1685–1689
1689
4 - Phenyl - trans - 1 - (2 - phenylcyclopropyl)- 1,2,3,6 -
tetrahydrozpyridine (21). A solution of the dinitropyr-
HR-CIMS. calcd for C H N0: 292.1704. Found:
20 21
292.1701.
1
6
idinium salt 22 (0.9 g, 2.6 mmol) and tranylcypromine
obtained from 0.9 g, 5.2 mmol of the corresponding
(
hydrochloride salt) in anhydrous butanol (30 mL) was
heated under reflux for 12 h. The dark red color that
formed initially slowly turned dark brown. The butanol
was removed in vacuo and an aqueous solution of the
residue was washed with dichloromethane (4ꢁ30 mL)
The water was removed under reduced pressure to
Acknowledgements
This work was supported by the National Institute of
Neurological and Communicative Disorders and
Strokes (NS 28792) and by the Harvey W. Peters Center
for the Study of Parkinson’s Disease.
1
afford the crude hygroscopic pyridinium chloride 24: H
NMR (DMSO-d ) d 9.25 (d, 2H, 2,6-PyH), 8.53 (d, 2H,
6
References and Notes
3
(
,5-PyH), 8.15 (m, 2H, PhH), 7.65 (m, 4H, PhH), 7.35
m, 4H, PhH), 4.72 (m, 1H, C H ), 3.12 (m, 1H, C H ),
1. Chiba, K.;Trevor, A. J.;Castagnoli, N., Jr. Biochem. Bio-
phys. Res. Comm. 1985, 128, 1228. Langston, J. W.;Irwin, I.;
Langston, E. B.;Forno, L. S. Neurosci. Lett. 1984, 48, 87.
Langston, J. W. Neurology 1996, 47, S153.
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Chem. Res. Toxicol. 1992, 5, 625.
. Silverman, R. B. Acc. Chem. Res. 1995, 28, 335.
. Musa, O. M.;Horner, J. H.;Shahin, H.;Newcomb, M. J.
Am. Chem. Soc. 1996, 118, 3862. Maeda, Y.;Ingold, K. U. J.
Am. Chem. Soc. 1980, 102, 328.
5. Franot, C.;Mabic, S.;Castagnoli, N., Jr.
Chem. 1998, 6, 283.
6. Anderson, A. Mechanistic Studies on the Monoamine Oxi-
dse Catalylzed Oxidation of 1,4-Disubstituted Tetra-
hydropyridine Derivatives, PhD in Chemistry, Virginia
3
4
3
4
2
.50 (s, H O), 2.25 (m, 1H, C H ) and 1.86 (m, 1H,
2 3 4
1
3
C H ); C NMR (DMSO-d ) d 155.0, 145.0, 137.5,
3
4
6
1
32.0, 131.8, 130.0, 126.5, 126.0, 127.8, and 123.8;UV
(
treated directly with excess NaBH in 25 mL methanol
MeOH) lmax 305 nm. A portion of this product was
4
3
4
ꢂ
removed in vacuo and the residue in 25 mL H O was
at 0 C. After stirring for 30 min, the solvent was
2
extracted with dichloromethane (2ꢁ20 mL). The com-
bined organic layer was dried over Na SO , filtered,
2
Bioorg. Med.
4
evaporated and the residue in 25 mL of ether was trea-
ted with ethereal oxalic acid. The precipitated oxalate
salt was recrystallized from methanol/ether (0.36 g,
B
ꢂ
1
4
5%): mp 181–182 C; H NMR (DMSO-d ) d 7.46–
6
Polytechnic Institute and State University, 1993–1997.
7
.27 (m, 10H, PhH), 6.17 (m, 1H, C5H), 3.55 (bs, 2H,
7
. Rimoldi, J.;Wang, Y.;Nimkar, S.;Kuttab, S.;Anderson,
A.;Birch, H.;Castagnoli, N., Jr. Chem. Res. Toxicol. 1995, 8,
03.
8. Guengerich, F. P.;Yun, C. H.;Macdonald, T. L. J. Biol.
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C6H), 3.10 (bs, 2H, C2H) 2.59 (bs, 2H, C3H), 2.37 (bs,
H, NCH), 2.23 (bs, 1H, NCHCH), 1.28 (m, 1H,
1
NCHCH ), 1.16 (m, 1H, NCHCH );
7
1
3
C NMR
2
2
(
DMSO-d ) d 139.5, 134.0, 128.2, 127.2, 125.7, 124.5,
6
1
2
M
19.9, 51.5, 47.4, 44.2, 26.0, 22.8;UV (MeOH) lmax 209,
9. Hanzlik, R. P.;Tullman, R. H. J. Am. Chem. Soc. 1982,
104, 2048. Macdonald, T. L.;Zirvi, K.;Burka, L. T.;Peyman,
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45 nm;GC ( t =8.7 min)-EIMS m/z (%) 275 (30,
R
.
+
), 184 (100), 155 (20), 115 (40), 91(45), 54 (18).
.
Anal. calcd for C H NO 0.16H O: C, 71.73;H, 6.25;
2
N, 3.80. Found: C, 71.78;H, 6.34;N, 3.78.
2
23
4
2
ard, R. J.;Shea, J. P.;Richards, L. E.;McDonald, T. L.
Am. Chem. Soc. 1984, 106, 6446.
J.
4-Phenyl-trans-1-(2-phenylcyclopropyl)-1,2,3,6-tetrahydro-
pyiridine-N-oxide (28). A solution of m-chloroperoxy-
10. Karki, S. B.;Dinnocenzo, J. P. Xenobiotica 1995, 7, 711.
Chen, H.;deGroot, M. J.;Vermeulen, N. P. E.;Hanzlik, R. P.
benzoic acid (0.63 g, 55%, 2 mmol) in dichloromethane
10 mL) was added dropwise to a solution of 21 (0.58 g,
J. Org. Chem. 1997, 62, 8227. Carlson, T. J.;Jones, J. P.;
Peterson, L.;Castagnoli, N., Jr.;Iyer, K. R.;Trager, W. F.
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11. Manchester, J. I.;Dinnocenzo, J. P.;Higgins, L.;Jones,
J. P. J. Am. Chem. Soc. 1997, 119, 5069.
(
ꢂ
2
.11 mmol) in dichloromethane at 0 C. The resulting
ꢂ
mixture was stirred at 0 C for 1 h then at room
temperature for 3 h. The reaction mixture was chroma-
tographed on a basic alumina column (30 g, eluent
1
2. Zhao, Z.;Mabic, S.;Kuttab, S.;Franot, C.;Castagnoli,
K.;Castagnoli, N., Jr. Bioorg. Med. Chem. 1998, 6, 2531.
13. Chiba, K.;Kubota, E.;Miykawa, E. T.;Kato, Y.;Ishi-
zaki, T. J. Pharmacol. Exp. Ther. 1988, 246, 1108.
5
% methanol in dichloromethane) to afford 28 (0.4 g,
1
6
H, PhH), 5.9 (m, 0.5 H, C4H of one diastereomer),
5
3
1
4%) as a powder: H NMR (CDCl ) d 7.3–7.0 (m, 10
3
1
1
1
1
4. Lu, A. Y.;Levin, W. Biochem. Biophys. Res. Commun.
972, 46, 1334.
5. Redinbough, M. G.;Turley, R. B. Anal. Biochem. 1986,
53, 267.
.7 (m, 0.5 H, C4H of second diastereomer), 4.03–
.94, (m, 2H, C6H), 3.6–3.5 (m, 2H, C2H), 3.07 (m,
H, NCH), 2.88 (m, 2H, C3H), 2.15 (m, 0.5H,
NHCHCH of one diastereomer), 1.95 (m, 1H, NHCH
of second diastereomer), 1.05 (m, 2H, NCH CHCH).
16. Genisson, Y.;Mehmandonst, M.;Marazano, C.;Das,
B. C. Heterocycles 1994, 39, 811.
2