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...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 cycli- zation. These γ,γ-difluorinated Goniothalamin analogues 4a-4i and their enanfiomers 6a--6i, together with several corresponding 7-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.展开更多
The first enantioselective total synthesis of 5-acetoxygoniothalamin 1 and 5-acetoxyisogoniothalamin oxide 2 was achieved through the Sharpless kinetic resolution of racemic secondary 2- furylmethanol 5 and the Mitsun...The first enantioselective total synthesis of 5-acetoxygoniothalamin 1 and 5-acetoxyisogoniothalamin oxide 2 was achieved through the Sharpless kinetic resolution of racemic secondary 2- furylmethanol 5 and the Mitsunobu reaction. At the same time we developed a short synthetic route for 6R-(+)-goniothalamin 3 and (6R, 7R, 8R)-(+)-goniothalamin oxide 4. And according to this route the configuration of 5-acetoxygoniothalamin 1 was confirmed as (5S, 6S).展开更多
基金National Natural Science Foundation of China，National Basic Research Program of China，Scientific Research Program of Sichuan University of Science & Engineering (Nos.2012RC17,2012RC15) are greatly acknowledged for funding this work
文摘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 cycli- zation. These γ,γ-difluorinated Goniothalamin analogues 4a-4i and their enanfiomers 6a--6i, together with several corresponding 7-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.
基金We are grateful to the National Natural Science Foundation of China(No.2017223)for financial support
文摘The first enantioselective total synthesis of 5-acetoxygoniothalamin 1 and 5-acetoxyisogoniothalamin oxide 2 was achieved through the Sharpless kinetic resolution of racemic secondary 2- furylmethanol 5 and the Mitsunobu reaction. At the same time we developed a short synthetic route for 6R-(+)-goniothalamin 3 and (6R, 7R, 8R)-(+)-goniothalamin oxide 4. And according to this route the configuration of 5-acetoxygoniothalamin 1 was confirmed as (5S, 6S).
