1942
Q. Fu, Z. Chen
SHORT PAPER
HRMS (ESI): m/z [M + Na]+ calcd for C20H16N2O5Na: 387.0951;
found: 387.0954.
Anal. Calcd for C27H21N3O9S: C, 57.55; H, 3.76; N, 7.46. Found: C,
57.73; N, 7.27; H, 3.62.
Anal. Calcd for C20H16N2O5: C, 62.82; H, 4.74; N, 7.33. Found: C,
62.75; H, 4.67; N, 7.26.
9-Nitrocamptothecin (1)
A solution of HCO2H (1.84 g, 0.04 mol) and Et3N (4.04 g, 0.04 mol)
in dioxane (10 mL) was added dropwise to a solution of 9-nitro-10-
(p-toluenesulfonyl)camptothecin (11.3 g, 0.02 mmol), Pd(AcO)2
(240 mg, 0.0001 mol) and DPPF (620 mg, 0.0001 mol) in dioxane
(226 mL) at 70 °C, under an argon atmosphere over a period of 1.5
h. After the addition was complete, the resulting mixture was con-
centrated in vacuo and the residue was extracted into CHCl3 (150
mL), washed with HCl (2 N, 50 mL), brine (50 mL) and dried with
Na2SO4. Concentration under vacuum gave a yellow powder (7.53
g) that was recrystallized from CHCl3 (75 mL) to give pure 1 (6.3 g,
77% yield, 99.4% purity) as a yellow powder.
1H NMR (300 MHz, CDCl3): d = 1.04 (t, J = 7.4 Hz, 3 H), 1.86–
1.94 (m, 2 H), 3.87 (s, 1 H), 5.72 (dd, J = 13.2 , 13.2 Hz, 2 H), 7.70
(s, 1 H), 7.71 (t, J = 7.9 Hz, 1 H), 8.48 (d, J = 7.8 Hz, 1 H), 8.56 (d,
J = 8.5 Hz, 1 H), 9.26 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 7.7, 31.6, 50.3, 66.2, 72.6, 98.9,
119.9, 120.8, 125.8, 127.2, 128.5, 131.5, 136.7, 145.1, 145.8, 148.8,
149.9, 153.7, 157.4, 173.6.
9-Nitro-10-hydroxycamptothecin (4)
Fuming nitric acid (7.8 g, 0.12 mol) was added dropwise to a sus-
pension of 3 (36.3 g, 0.1 mol) in acetic acid (180 mL) at r.t., during
which the mixture gradually became a clear yellow. The reaction
mixture was stirred for a further 1 h, then diluted with H2O (500
mL). The precipitated product was filtered from the solution,
washed with H2O (100 mL) and dried at 40 °C under vacuum to
give 4 as a yellow powder (34.2 g, 83% yield).
1H NMR (300 MHz, DMSO-d6): d = 0.87 (t, J = 6.9 Hz, 3 H), 1.85
(q, J = 7.5 Hz, 2 H), 5.21 (s, 2 H), 5.40 (s, 2 H), 6.52 (s, 1 H), 7.27
(s, 1 H), 7.64 (d, J = 9.4 Hz, 1 H), 8.20 (d, J = 9.3 Hz, 1 H), 8.39 (s,
1 H).
13C NMR (75 MHz, DMSO-d6): d = 7.8, 30.3, 50.6, 65.2, 72.3,
96.6, 119.0, 121.2, 122.7, 123.8, 132.5, 133.8, 141.5, 145.0, 149.5,
149.9, 150.9, 156.7, 172.5.
HRMS (ESI): m/z [M + Na]+ calcd for C20H15N3O7Na: 432.0802;
found: 432.0883.
HRMS (ESI): m/z [M + H]+ calcd for C20H16N3O6: 394.1034; found:
394.1039.
Anal. Calcd for C20H15N3O7: C, 58.68; H, 3.69; N, 10.27. Found: C,
58.54; H, 3.57; N, 10.12.
Anal. Calcd for C20H15N3O6: C, 61.07; H, 3.84; N, 10.68. Found: C,
61.01; H, 3.71; N, 10.50.
9-Nitro-10-(p-toluenesulfonyl)camptothecin
TsCl (19.85 g, 0.105 mmol) was added to a solution of 4 (40.9 g, 0.1
mol) and Et3N (10.6 g, 0.105 mol) in CH2Cl2 (400 mL) at r.t. and
the reaction mixture was stirred for 12 h. The reaction was quenched
with H2O (150 mL) and the organic layer was separated. The aque-
ous layer was extracted with CH2Cl2 (200 mL), the combined or-
ganic layers were washed with brine (150 mL) and dried with
Na2SO4. Concentration under vacuum gave the crude product as a
yellow powder (54.2 g mass balance). The crude product was re-
crystallized (CHCl3–PE 1:1, 1100 mL) to give the pure product as a
light-yellow powder (43 g, 76% yield).
1H NMR (300 MHz, CDCl3): d = 1.04 (t, J = 7.3 Hz, 3 H), 1.85–
1.91 (m, 2 H), 2.48 (s, 3 H), 3.85 (s, 1 H), 5.31 (s, 2 H), 5.33 (d, J =
16.5 Hz, 1 H), 5.70 (d, J = 16.8 Hz, 1 H), 7.39 (d, J = 6.8 Hz, 2 H),
7.68 (s, 1 H), 7.82 (d, J = 8.4 Hz, 2 H), 7.97 (d, J = 9.4 Hz, 1 H),
8.31 (s, 1 H), 8.42 (d, J = 9.3 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 7.7, 21.8, 31.6, 50.1, 66.2, 72.6,
76.5, 77.0, 77.4, 99.1, 120.2, 120.5, 125.5, 125.8, 128.6, 130.2,
131.2, 131.4, 134.3, 139.7, 139.9, 144.8, 146.2, 146.8, 150.0, 154.2,
157.3, 173.6.
HRMS (ESI): m/z [M + Na]+ calcd for C27H21N3O9SNa: 586.0891;
found: 586.0808.
Acknowledgment
We acknowledge financial support from West Light of the Chinese
Academy of Science.
Reference
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Synthesis 2006, No. 12, 1940–1942 © Thieme Stuttgart · New York