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Total Synthesis and Anticancer Activity of (+)-Hypercalin?C and Congeners.

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 sp3 -C sp2 Suzuki-Miyaura coupling with an ?-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.

SUBMITTER: Tao Y

PROVIDER: S-EPMC6438696 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Total Synthesis and Anticancer Activity of (+)-Hypercalin C and Congeners.

Tao Yongfeng Y Reisenauer Keighley K Taube Joseph H JH Romo Daniel D

Angewandte Chemie (International ed. in English) 20190201 9

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 sp3 -C sp2 Suzuki-Miyaura coupling with an α-bromo enolether also revealed an unexpected C-H activat ...[more]

PMID: 30600887

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