Tether mediated synthetic efforts toward the total synthesis of Fostriecin and 8-epi-fostriecin employing both ring-closing metathesis (RCM) and cross metathesis (CM) are presented.  Fostriecin, an antitumor antibiotic isolated from Streptomyces pulveraceus, is the most potent inhibitor of protein phosphatases 2A and 4, known to-date (IC50s 3.2 nM and 3 nM, respectively).  It has been shown to be active against L1210 and P388 leukemia cells in vivo and in vitro against leukemia, lung, breast, and ovarian cancer cells. Diastereoselective ring-closing metathesis reaction, regioselective oxidation, diastereoselective Grignard addition and cross metathesis, all mediated by a temporary phosphate tether, have established a scaleable route toward the goal of total and analog synthesis of Fostriecin and 8-epi-Fostriecin.

Phosphate tether-mediated approaches toward the total synthesis of fostriecin and 8-<i>epi</i>?- fostriecin

244th National Meeting (2012)

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Phosphate tether-mediated approaches toward the total synthesis of fostriecin and 8-epi?- fostriecin