Method of synthesizing camptothecin-relating compounds

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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Reexamination Certificate

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07126000

ABSTRACT:
The present invention is to prepare efficiently 2′-amino-5′-hydroxypropiophenone corresponding to the AB-ring part of camptothecin (CPT) skeleton and a tricyclic ketone corresponding to the CDE-ring part in order to provide efficiently CPT by the total synthesis, which is a starting material for irinotecan hydrochloride and various kinds of camptothecin derivatives, and to provide stably CPT and its derivatives.

REFERENCES:
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patent: 845464 (1998-06-01), None
patent: WO 94/11376 (1994-05-01), None
Curran, Dennis P. et al., “Cascade Radical Reactions of Isonitriles: A Second-Generation Synthesis of (20S)-Camptothecin, Topotecan, Irinotechan, and GI-147211C**,” Angew. Chem. Int. Ed. Engl. 1995, 34, 2683-2684.
Josien, Hubert et al., “A General Synthetic Approach to the (20S)-Camptothecin Family of Antitumor Agents by a Regiocontrolled Cascade Radical Cyclization of Aryl Isonitriles,” Chemistry a European Journal, 1998, vol. 4, No. 1, pp. 67 to 83.
Gann to Kagaku Ryohou 17, p. 115-120, 1990 with an abridged English translation; p. 116, right column lines 9 from the bottom to last line.
She, Wang, et al., “Concise Total Syntheses of dl-Camptothecin and Related Anticancer Drugs,” J. Org. Chem. 1993, 58, 611-617.
Henegar, Kevin E., et al., “Practical Asymmetric Synthesis of (S)-4-Ethyl-7,8-dihydro-4-hydroxy-1H-pyranol[3,4-f]indolizine-3,6,10(4H)-trione, a Key Intermediate for the Synthesis of Irinotecan and Other Camptothecin Analogs,” J. Org. Chem., 1997, vol. 62, No. 19, pp. 6588 to 6597.
Sawada, Seigo, et al., “Synthesis and Antitumor Activity of 20(S)-Camptothecin Derivatives: Carbamate-Linked, Water-Soluble Derivatives of 7-Ethyl-10-hydroxycamptothecin,” T. Chem. Pharm. Bull. 1991, 39, 1446.

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