Organic Chemistry

Asymmetric Total Synthesis of C9’-epi-Sinefungin

Ludovic Decultot Harvard University Department of Chemistry and Chemical Biology


The natural nucleoside (+)-sinefungin, structurally similar to cofactor S-adenosyl-L-methionine (SAM), inhibits various SAM-dependent methyltransferases (MTs). Access to sinefungin analogues could serve as the basis for the rational design of small-molecule methyltransferase inhibitors. We developed a route to the unnatural C9’ epimer of sinefungin that employed a diastereoselective Overman rearrangement to install the key C6’ amino stereocenter. The ability for late stage modification is highlighted, opening an avenue for the discovery of new MTs inhibitors.


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Supplementary material

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EpiSinefungin Decultot Policarpo ChemRxiv 2020 SI
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EpiSinefungin Xray Cpd12 ChemRxiv 2020

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