July 2001
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temperature and worked up as usual to afford 1.1 g of (E)-4-O-acetyl- (12H, s, CH3CO–), 3.42 (4H, overlapped with solvent, H-2, 13), 3.51 (8H,
coumaric acid. One gram of (E)-4-O-acetylcoumaric acid in 7 ml of SOCl2 m, H-4, 6, 9, 11), 6.48 (2H, m), 6.81 (2H, m), 7.08 (8H, m), 7.55 (12H, m)
was refluxed at 80 °C for 16 h, then the mixture was evaporated to dryness to (H-ac-cou).
give (E)-4-O-acetylcoumaroyl chloride.
N1,N5,N10,N14-Tetra-p-coumaroylspermine (7)13)
: White powder, 91%
To (E)-4-O-acetylcoumaroyl chloride (0.5 mmol) in 15 ml tetrahydrofuran yield, negative ESI-MS: m/z 785 ([MϪH]Ϫ, 7). 1H-NMR (300 MHz,
(THF) was added 15 ml THF solution of 0.17 mmol of spermidine [or CD3OD): d: 1.69 (4H, m, H-7, 8), 1.86 (4H, m, H-3, 12), 3.31 (4H, over-
0.17 mmol of tris (2-aminoethyl)amine, or 0.13 mmol of spermine, or lapped with solvent, H-2, 13), 3.54 (8H, m, H-4, 6, 9, 11), 6.40 (2H, m),
0.25 mmol of putrescine, or 0.10 mmol of tetraethylenepentamine], and 6.79 (10H, m), 7.40 (12H, m) (H-cou).
100 ml triethylamine. The mixture was stirred at room temperature overnight
N1,N4,N7,N10,N13-Penta(4-O-acetylcoumaroyl)tetraethylenepentamine
and then water (20 ml) was added. After being concentrated, the residue was (8a): White powder, 51% yield, positive FAB-MS: m/z 1130 ([Mϩ1]ϩ, 25),
purified with ODS column chromatography eluted with H2O–MeOH (6 : 4— 307 (13). 1H-NMR (300 MHz, CDCl3): d: 2.30 (15H, s, CH3CO–), 3.5—3.8
0 : 10) to afford the corresponding 4-O-acetylcoumaroylamides (1a, 5a—
(16H, m, H-2, 3, 5, 6, 8, 9, 11, 12), 6.3—6.5 (2H, m), 6.9—7.7 (28H, m) (H-
8a). To a solution of 4-O-acetylcoumaroylamide (50 mg) in CH3OH–THF ac-cou). HR-FAB-MS m/z 1130.4347 (Calcd for C63H64N5O15 [MϩH]ϩ,
(1 : 1) was added 0.1 N KOH/MeOH 12 ml. After stirring for 1.5 h at room 1130.4400).
temperature, the solution was neutralized with 0.1 N HCl and purified by
N1,N4,N7,N10,N13-Penta-p-coumaroyltetraethylenepentamine (8): White
ODS column chromatography eluted with H2O–MeOH (8 : 2—0 : 10) to give powder, 87% yield, positive FAB-MS: m/z 920 ([Mϩ1]ϩ, 7), 307 (15), 289
the corresponding coumaroylamides (1, 5—8).
(10). 1H-NMR (300 MHz, CD3OD): d: 3.4—3.9 (16H, m, H-2, 3, 5, 6, 8, 9,
N1,N5,N10-Tri(4-O-acetylcoumaroyl)spermidine (1a): White powder, 69% 11, 12), 6.2—6.5 (2H, m), 6.6—7.0 (13H, m), 7.2—7.6 (15H, m) (H-ac-
yield, positive FAB-MS: m/z 710 ([Mϩ1]ϩ, 15). 1H-NMR (300 MHz, cou). HR-FAB-MS m/z 920.3834 (Calcd for C53H54N5O10 [MϩH]ϩ,
CD3OD): d: 1.68 (4H, m, H-7, 8), 1.89 (2H, m, H-3), 2.25 (9H, s, CH3CO–), 920.3872).
3.31 (4H, overlapped, H-2, 9), 3.58 (4H, m, H-4, 6), 6.52 (d,
HIV PR Assay HIV PR assay kit (3700 Horizon Drive, King of Prussia,
Jϭ16.0 Hz)/6.57 (d, Jϭ16.0 Hz), 6.57 (1H, d, Jϭ16.0 Hz), 6.97 (2H, m), PA 19406, Kit Lot No 1) was used. Assay was performed and inhibitory ac-
7.11 (5H, m), 7.58 (9H, m) (aromatic and olefinic protons). HR-FAB-MS tivity was calculated as described previously.14) Acetyl pepstatin was used as
m/z 710.3086 (Calcd for C40H44N3O9 [MϩH]ϩ, 710.3078).
a positive control and showed an IC50 of 0.07 mM.
Tris[2-(4-O-acetylcoumaroyl)aminoethyl]amine (5a): White powder, 53%
yield, positive FAB-MS: m/z 711 ([Mϩ1]ϩ, 30), 492 (10). 1H-NMR (300 References
MHz, CD3OD): d: 2.29 (9H, s, CH3CO–), 2.70 (6H, m, H-1, 1Ј, 1Љ), 3.43
(6H, m, H-2, 2Ј, 2Љ), 6.63 (3H, d, Jϭ15.8 Hz, H-ac-cou-8), 6.86 (6H, d,
Jϭ8.4 Hz, H-ac-cou-3, 5), 7.25 (6H, d, Jϭ8.4 Hz, H-ac-cou-2, 6), 7.39 (3H,
d, Jϭ15.8 Hz, H-ac-cou-7). HR-FAB-MS m/z 711.3002 (Calcd for
C39H43N4O9 [MϩH]ϩ, 711.3031).
Tris(2-p-coumaroylaminoethyl)amine (5): White powder, 89% yield, posi-
tive FAB-MS: m/z 585 ([Mϩ1]ϩ, 25), 307 (15). 1H-NMR (300 MHz,
CD3OD): d: 2.67 (6H, t, Jϭ5.1 Hz, H-1, 1Ј, 1Љ), 3.39 (6H, t, Jϭ5.1 Hz, H-2,
2Ј, 2Љ), 6.49 (3H, d, Jϭ15.7 Hz, H-cou-8), 6.59 (6H, d, Jϭ8.5 Hz, H-cou-3,
6), 7.19 (6H, d, Jϭ8.5 Hz, H-cou-2, 6), 7.39 (3H, d, Jϭ15.7 Hz, H-cou-7).
HR-FAB-MS m/z 585.2714 (Calcd for C33H37N4O6 [MϩH]ϩ, 585.2714).
N1,N6-Di(4-O-acetylcoumaroyl)putrescine (6a): White powder, 64%
yield, positive FAB-MS: m/z 465 ([Mϩ1]ϩ, 15), 307 (10), 289 (8). 1H-NMR
(300 MHz, CDCl3–CD3OD 1 : 2): d: 1.64 (4H, m, H-3, 4), 2.32 (6H, s,
CH3CO–), 3.36 (4H, overlapped with solvent, H-2, 5), 6.49 (2H, d,
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Jϭ15.0 Hz, H-ac-cou-8), 7.11 (4H, d, Jϭ8.5 Hz, H-ac-cou-3, 5), 7.53 (2H, d, 10) Robinson W. E. Jr., Reinecke M. G., Abdel-Malek S., Jia Q., Chow S.
Jϭ15.0 Hz, H-ac-cou-7), 7.55 (4H, d, Jϭ8.5 Hz, H-ac-cou-2, 6). HR-FAB-
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(1996).
MS m/z 465.2016 (Calcd for C26H29N2O6 [MϩH]ϩ, 465.2026).
N1,N6-Di-p-coumaroylputrescine (6)12): White powder, 90% yield, no
1
peak appeared in ESI-MS, H-NMR (300 MHz, CD3OD): d: 1.64 (4H, m,
H-3, 4), 3.36 (4H, overlapped with solvent, H-2, 5), 6.43 (2H, d, Jϭ16.0 Hz, 12) Martin-Tanguy J., Cabanne F., Perdrizet E., Martin C., Phytochemistry,
H-cou-8), 6.82 (4H, d, Jϭ8.6 Hz, H-cou-3, 5), 7.43 (4H, d, Jϭ8.6 Hz, H-
cou-2, 6), 7.48 (4H, d, Jϭ16.0 Hz, H-cou-7).
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A1 12 Jul 2000, 11 pp.
N1,N5,N10,N14-Tetra(4-O-acetylcoumaroyl)spermine (7a)13): White pow-
der, 70% yield, positive ESI-MS: m/z 978 ([MϩNa]ϩ, 100), 955 ([MϩH]ϩ, 14) Ma C-M., Nakamura N., Miyashiro H., Hattori M., Shimotohono K.,
75). negative ESI-MS: m/z 953 ([MϪH]Ϫ, 7). 1H-NMR (300 MHz,
CDCl3–CD3OD 2 : 1): d: 1.68 (4H, m, H-7, 8), 1.84 (4H, m, H-3, 12), 2.31
Chem. Pharm. Bull., 47, 141—145 (1999).