Total Synthesis and Anticancer Activity of (+)‐Hypercalin C and Congeners
- 2 January 2019
- journal article
- research article
- Published by Wiley in Angewandte Chemie International Edition
- Vol. 58 (9) , 2734-2738
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.Keywords
Funding Information
- Welch Foundation (AA-1280)
- National Institute of General Medical Sciences (R37 GM052964)
- Susan G. Komen for the Cure (CCR18548469)
- Cancer Prevention and Research Institute of Texas (RP180771)
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