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Total Synthesis and Anticancer Activity of (+)-Hypercalin C and Congeners
Yongfeng Tao1, Keighley Reisenauer2, Joseph H Taube2
1Department of Chemistry and Biochemistry, Baylor University, 101 Bagby Ave., Waco, TX, 76798, USA.
Abstract:
The hypercalins are dearomatized acylphloroglucinols with a pendant complex cyclopentane ring that exhibit activity against several cancer cell lines. We report the first total synthesis of (+)-hypercalin C employing a convergent strategy that enabled the dissection of the essential structural features required for the observed anticancer activity. A strategic disconnection involving an unusual C -C Suzuki-Miyaura coupling with an α-bromo enolether also revealed an unexpected C-H activation. This strategy targeted designed analogues along the synthetic route to address particular biological questions. These results support the hypothesis that hypercalin C may act as a proton shuttle with the dearomatized acylphloroglucinol moiety being essential for this activity.
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