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Ovatodiolides: Scalable Protection‐Free Syntheses, Configuration Determination, and Biological Evaluation against Hepatic Cancer Stem Cells
Author(s) -
Xiang Junhong,
Ding Yahui,
Li Jiaxin,
Zhao Xiuhe,
Sun Yuanjun,
Wang Da,
Wang Liang,
Chen Yue
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201904096
Subject(s) - metathesis , ring closing metathesis , chemistry , tandem , butenolide , stereochemistry , combinatorial chemistry , natural product , ring (chemistry) , salt metathesis reaction , protecting group , population , lactone , organic chemistry , materials science , alkyl , demography , sociology , composite material , polymerization , polymer
A concise, scalable, six‐step (longest linear sequence) synthetic route to ovatodiolide scaffolds was developed for the first time. This protecting‐group‐free route features tandem ring‐opening metathesis/ring‐closing metathesis reactions to install the macrocycle‐fused butenolide ring and a tandem allylboration/lactonization to build the α‐methylene‐γ‐lactone. Our syntheses have enabled the determination of the hitherto unknown stereochemical configurations of this family of natural products. Preliminary tests of structure–activity relationships were conducted with four natural ovatodiolides and three analogues. Further assays indicated that the synthetic natural product isoovatodiolide can significantly decrease the population of hepatic cancer stem cells and reduce the tumorsphere‐forming capability of HepG2 cells.