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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 international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201812909
Subject(s) - moiety , chemistry , total synthesis , cyclopentane , stereochemistry , combinatorial chemistry , ring (chemistry) , cancer cell lines , cancer cell , organic chemistry , cancer , biology , genetics
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.