Mimicry of Annonaceous Acetogenins:  Enantioselective Synthesis of a (4R)-Hydroxy Analogue Having Potent Antitumor Activity

• Published in: Journal of organic chemistry 2002-05, Vol.67 (10), p.3404-3408
• Main Authors: Jiang, Sheng, Liu, Zhong-Hai, Sheng, Gang, Zeng, Bu-Bing, Cheng, Xiao-Guang, Wu, Yu-Lin, Yao, Zhu-Jun
• Format: Article
• Language: English
• Subjects: Annonaceae - chemistry; Antineoplastic Agents, Phytogenic - chemical synthesis; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Cells, Cultured - drug effects; Chemistry; Colonic Neoplasms; Dose-Response Relationship, Drug; Doxorubicin - pharmacology; Drug Screening Assays, Antitumor; Exact sciences and technology; Furans - chemical synthesis; Furans - chemistry; Furans - pharmacology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Humans; Inhibitory Concentration 50; Intestines; Molecular Mimicry; Molecular Structure; Organic chemistry; Preparations and properties; Stereoisomerism; Tumor Cells, Cultured - drug effects
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo016396u

The (4R)-hydroxylated analogues of annonaceous acetogenin mimicking compound 2 were designed and synthesized structurally on the basis of the naturally occurring annonaceous acetogenin bullatacin, which was discovered as a typical member of the novel family of polyketides with potent cytotoxicity, antitumoral, and other biological activities. The preliminary screenings show that the IC50 values of 2 were 1.6 × 10-3 and 8 × 10-2 μg/mL against HT-29 and HCT-8, respectively. A remarkable enhancement effect was observed by the activity comparison of 1c and its (4R)-hydroxylated analogue 2.