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Synthesis and Antitumor Activity Evaluation of γ ‐Monofluorinated and γ , γ ‐Difluorinated Goniothalamin Analogues
Author(s) -
Yang Yi,
Yang Zhenjun,
Cheng Chunru,
Qing Fengling
Publication year - 2013
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201300227
Subject(s) - chemistry , stereocenter , stereochemistry , aryl , enantiomer , stille reaction , diastereomer , cancer cell lines , combinatorial chemistry , enantioselective synthesis , organic chemistry , cancer cell , cancer , catalysis , medicine , alkyl
Abstract A series of novel γ , γ ‐difluorinated Goniothalamin analogues 4a – 4i and 6a – 6i were synthesized. The key steps included the construction of C‐5 stereocenter adjacent to gem ‐difluoromethylene group by way of lipase AK catalyzed kinetic resolution, the introduction of aryl group via Stille coupling, and lactonization by 1,5‐oxidative cyclization. These γ , γ ‐difluorinated Goniothalamin analogues 4a – 4i and their enantiomers 6a – 6i , together with several corresponding γ ‐monofluorinated Goniothalamin analogues were biologically evaluated against four different cancer cell lines. Compound 7h showed a nearly equivalent potency as the parent ( R )‐Goniothalamin in the micromolar range. The different fluorine effects between fluoromethylene and gem ‐difluoromethylene on antitumor activity were discussed through the analysis of bioassay data.