Total Synthesis of (+)-Camptothecin via an Intramolecular Palladium-Catalyzed Cyclization Strategy

Subhash P. Chavan; Ashok B. Pathak; Uttam R. Kalkote

doi:10.1055/s-2007-991054

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Synlett 2007(17): 2635-2638
DOI: 10.1055/s-2007-991054

LETTER

Total Synthesis of (+)-Camptothecin via an Intramolecular Palladium-Catalyzed Cyclization Strategy

Subhash P. Chavan*, Ashok B. Pathak, Uttam R. Kalkote
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune 411008, India
e-Mail: Sp.chavan@ncl.res.in;

Further Information

Publication History

Received 1 August 2007
Publication Date:
25 September 2007 (online)

Abstract
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Abstract

The novel cascade intramolecular Pd-catalyzed cyclization followed by aromatization for the construction of d ring of (+)-camptothecin as a key step is demonstrated.

Key words

natural products - alkaloids - antitumor - palladium - cyclizations

References and Notes

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14

Synthesis of Compound 23: Procedure for the Pd-Catalyzed Cyclization Reaction
To a stirred solution of compound 22 (0.2 g, 0.61 mmol) in DMF (3.0 mL) and H₂O (1.0 mL) was added PdCl₂ (0.007 g, 0.061 mmol) and CuCl₂·2H₂O (0.22 g, 1.2 mmol). The resultant dark green solution was heated at 95 °C for 8 h. After the disappearance of starting material (TLC), the reaction mixture was cooled to r.t. Then, H₂O (10 mL) was added and extracted with Et₂O (3 × 15 mL). The combined organic layers were washed with H₂O (3 × 10 mL), brine (10 mL), dried over anhyd Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by flash column chromatog-raphy (SiO₂) using EtOAc-PE (6:4) as an eluent to furnish cyclized product 23 as a pale yellow solid in 54% yield, mp 97-100 °C.
Spectroscopic Data for Compound 23
IR (CHCl₃): ν_max = 1728, 1658, 1604 cm^-1. ¹H NMR (400 MHz, CDCl₃ and CCl₄): δ = 1.44 (3 H, t, J = 7.2 Hz), 2.46 (3 H, s), 4.46 (2 H, q, J = 7.2 Hz), 5.27 (2 H, s), 7.21 (1 H, s), 7.66 (1 H, t, J = 8.0 Hz), 7.82 (1 H, t, J = 8.0 Hz), 7.92 (1 H, d, J = 8.0 Hz), 8.22 (1 H, d, J = 8.0 Hz), 8.37 (1 H, s) ppm. ¹³C NMR (100 MHz, CDCl₃ and CCl₄): δ = 14.3, 20.4, 50.15, 61.5, 103.5, 124.0, 127.95, 128.1, 129.1, 129.8, 130.5, 131.0, 136.0, 145.7, 148.9, 151.0, 152.4, 158.4, 166.3 ppm. ESI-MS: m/z = 321 [M + H]⁺, 343 [M + Na]⁺. Anal. Calcd (%) for C₁₉H₁₆N₂O₃: C, 71.24; H, 5.03; N, 8.74. Found: C, 71.19; H, 5.11; N, 8.69.