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Probing the SAR of dEpoB via Chemical Synthesis: A Total Synthesis Evaluation of C26-(1,3-dioxolanyl)-12,13-desoxyepothilone B

2002; American Chemical Society; Volume: 67; Issue: 22 Linguagem: Inglês

10.1021/jo020180q

1520-6904

Mark D. Chappell, Christina R. Harris, Scott D. Kuduk, Aaron Balog, Zhicai Wu, Fei Zhang, Chul Bom Lee, Shawn J. Stachel, Samuel J. Danishefsky, Ting‐Chao Chou, Yongbiao Guan,

Advanced Synthetic Organic Chemistry

A practical total synthesis of 26-(1,3-dioxolanyl)-12,13-desoxyepothilone B (26-dioxolanyl dEpoB) was accomplished in a highly convergent manner. A novel sequence was developed to produce the vinyl iodide segment 17 in high enantiomeric excess, which was used in a key B-alkyl Suzuki merger. Subsequently, a Yamaguchi macrocyclization formed the core lactone, while a selective oxidation and a late stage Noyori acetalization incorporated the dioxolane functionality. Sufficient amounts of synthetic 26-dioxolane dEpoB were produced using this sequence for an in vivo analysis in mice containing xenograft CCRF-CEM tumors.