An Efficient Synthesis of ABT-263,
a Novel Inhibitor of Antiapoptotic Bcl-2 Proteins

Guangjun Wang; Hushan Zhang; Jing Zhou; Chengyong Ha; Duanqing Pei; Ke Ding

doi:10.1055/s-2008-1067129

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Synthesis 2008(15): 2398-2404
DOI: 10.1055/s-2008-1067129

PAPER

An Efficient Synthesis of ABT-263, a Novel Inhibitor of Antiapoptotic Bcl-2 Proteins

Guangjun Wang^a,b,c, Hushan Zhang^b, Jing Zhou^b, Chengyong Ha^a, Duanqing Pei^b, Ke Ding*^b
^a Key Laboratory of Cellulose and Lignocellulosics Chemistry, Guangzhou Institute of Chemistry, Chinese Academy of Sciences, Guangzhou 510650, Guangdong, P. R. of China
^b Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, International Business Incubator A-3, Guangzhou Science Park, Guangzhou 510663, Guangdong, P. R. of China
Fax: +86(20)32290485; e-Mail: ding_ke@gibh.ac.cn;
^c Graduate School of the Chinese Academy of Sciences, Beijing 100039, Beijing, P. R. of China

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Publication History

Received 27 February 2008
Publication Date:
11 June 2008 (online)

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Abstract

ABT-263, a newly developed Bcl-2 inhibitor, was efficiently synthesized. The key intermediates 4-(4-{[2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-enyl]methyl}piperazin-1-yl)benzoic acid and 4-fluoro-3-[(trifluoromethyl)sulfonyl]benzenesulfonamide were efficiently prepared by a three-component Mannich reaction and by nucleophilic fluorination of 1-nitro-2-[(trifluoromethyl)sulfonyl]benzene as the key steps, respectively. Our work may lay a foundation for a new process development of this promising anticancer drug candidate.

Key words

Bcl-2 family protein inhibitor - anticancer drugs - ABT-263 - synthesis - sulfonamides

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