Enantioselective Syntheses of FR901464 and Spliceostatin A: Potent Inhibitors of Spliceosome

Enantioselective syntheses of FR901464 and spliceostatin A, potent spliceosome inhibitors, are described. The synthesis of FR901464 has been accomplished in a convergent manner in 10 linear steps (20 total steps). The <i>A</i>-tetrahydropyran ring was constructed from (<i>R</i>)-isopropylidene glyceraldehyde. The functionalized tetrahydropyran <i>B</i>-ring was synthesized utilizing a Corey–Bakshi–Shibata reduction, an Achmatowicz reaction, and a stereoselective Michael addition as the key steps. Coupling of <i>A</i>- and <i>B</i>-ring fragments was accomplished via cross-metathesis