59554-12-0Relevant articles and documents
Total synthesis of griseusins and elucidation of the griseusin mechanism of action
Zhang, Yinan,Ye, Qing,Ponomareva, Larissa V.,Cao, Yanan,Liu, Yang,Cui, Zheng,Van Lanen, Steven G.,Voss, S. Randal,She, Qing-Bai,Thorson, Jon S.
, p. 7641 - 7648 (2019)
A divergent modular strategy for the enantioselective total synthesis of 12 naturally-occurring griseusin type pyranonaphthoquinones and 8 structurally-similar analogues is described. Key synthetic highlights include Cu-catalyzed enantioselective boration-hydroxylation and hydroxyl-directed C-H olefination to afford the central pharmacophore followed by epoxidation-cyclization and maturation via diastereoselective reduction and regioselective acetylation. Structural revision of griseusin D and absolute structural assignment of 2a,8a-epoxy-epi-4′-deacetyl griseusin B are also reported. Subsequent mechanistic studies establish, for the first time, griseusins as potent inhibitors of peroxiredoxin 1 (Prx1) and glutaredoxin 3 (Grx3). Biological evaluation, including comparative cancer cell line cytotoxicity and axolotl embryo tail inhibition studies, highlights the potential of griseusins as potent molecular probes and/or early stage leads in cancer and regenerative biology.
