Atroposelective Heck Macrocyclization: Enantioselective Synthesis of Bis(bibenzylic) Natural Products

The Heck protocol was applied for the first time to the atroposelective synthesis of macrocyclic natural products. As ring closure to bis(bibenzyls) of the isoplagiochin type leads to a configurationally stable biaryl axis in the molecule, cyclization could be conducted atroposelectively in the presence of a chiral BINAP ligand

Dpp3 expression levels of BWP17-<i>DPP3-GFP</i> cells induced by bisbibenzyls.

<p>Values represent the increased folds of Dpp3 treated by tested agents compared with control. A) and B) Cells were treated with A1 and FLC at 37°C for 12 hours and then observed by CLSM and the Dpp3 expresson was quantitatively measured based on the fluorescence intensity. C) Fluorescence intensity of <i>C.albicans</i> cells pretreated with the tested agents was measured using a Multifunctional Microplater Reader after biofilm formation.</p

Phase-contrast micrographs of BWP-<i>DPP3-GFP</i> cells challenged by bisbibenzyls compounds within 12 hours.

<p>A) <i>Candida albicans</i> cells grown in RPMI 1640 broth medium was captured using an Olympus fluorescent microscope. The results showed that cells co-incubated with A1 (16 µg/ml) displayed yeast cells, cells with no drugs formed mycelium after three hours and maintained substantial growth of hyphae. B) Cells grown on Spider solid media were photographed from 2 d to 5 d using 4× objectives of an Olympus fluorescent microscope.</p

Biofilm formed of BWP17-<i>DPP3-GFP</i> cells pretreated with bisbibenzyls compounds.

<p>A) Quantitative measurement of inhibition of biofilm formation with Microplate Reader. B) Confocal micrographs of BWP17-<i>DPP3-GFP</i> cells cultured in RPMI 1640 for 48 hours. C) Cells were stained with alamar blue and cultured for 4–6 hours in dark, the supernatant would become pink when cells grow into biofilm, otherwise turn into blue. The test was performed in quadruplicate. A11 represents the compounds that biofilm inhibitory activity >64 µg/ml, bk represents blank control and nk represents negative control.</p

Farnesol production of BWP17-<i>DPP3-GFP</i> cells stimulated by bisbibenzyls.

<p>The cells were pretreated with A1, A3, A5 and FLC at 37°C for 12 hours and the farnesol amounts were determined by HPLC-MS. A) The retention time of farnesol eluting at 20.29 min. B) MS profile showed a molecular ion of m/z 221.2 and 222.2. C) Values of ordinate represents the increased folds of farnesol treated by tested agents compared with control.</p