Premium
Total Synthesis and Anticancer Activity of (+)‐Hypercalin C and Congeners
Author(s) -
Tao Yongfeng,
Reisenauer Keighley,
Taube Joseph H.,
Romo Daniel
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201812909
Subject(s) - moiety , chemistry , total synthesis , cyclopentane , stereochemistry , ring (chemistry) , combinatorial chemistry , cancer cell lines , biological activity , biochemistry , cancer cell , organic chemistry , cancer , biology , genetics , in vitro
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 Csp3–Csp2Suzuki–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.