2. Convergent Synthesis of Fluorescence-Labeled Probes of Annonaceous Acetogenins and Visualization of Their Cell Distribution
Naoto Kojima, Takekuni Morioka, Daisuke Urabe, Masahiro Yano, Yuki Suga, Naoyoshi Maezaki, Ayako Ohhashi-Kobayashi, Yasuyuki Fujimoto, Masatomo Maeda, Takao Yamori, Takehiko Yoshimitsu, and Tetsuaki Tanaka, Bioorg. Med. Chem., 18, 8630-8641 (2010).
Abstract:The convergent synthesis of fluorescence-labeled solamin, an antitumor Annonaceous acetogenin, was accomplished by two asymmetric alkynylations of 2,5-diformyl tetrahydrofuran with an alkyne tagged with fluorescent groups and another alkyne with an α,β-unsaturated γ-lactone. Assay for the growth inhibitory activity against human cancer cell lines revealed that the probe with the fluorescent groups at the end of the hydrocarbon chain may have the same mode of action as natural acetogenins. The merged fluorescence of dansyl-labeled solamin and MitoTracker Red suggests that Annonaceous acetogenins localize in the mitochondria.
1. Asymmetric Total Synthesis of (+)-Hexachlorosulfolipid, a Cytotoxin Isolated from Adriatic Mussels
Takehiko Yoshimitsu, Naoya Fukumoto, Ryo Nakatani, Naoto Kojima and Tetsuaki Tanaka, J. Org. Chem, 75, 5425–5437 (2010).
Abstract: The enantioselective total synthesis of (+)-hexachlorosulfolipid, a cytotoxin found in the Adriatic mussel Mytilus galloprovincialis, is described. The unique chlorinated hydrocarbon motif of the lipid is successfully furnished by a series of dichlorination reactions of chiral epoxides with chlorophosphonium reagent generated in situ from Ph3P/NCS. The present total synthesis has allowed the confirmation of the absolute configuration of the natural cytotoxic (+)-hexachlorosulfolipid originally proposed by Fattorusso, Ciminiello, and co-workers.