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. 2013 Oct 4;15(19):5088-91.
doi: 10.1021/ol4024634. Epub 2013 Sep 19.

Enantioselective syntheses of FR901464 and spliceostatin A: potent inhibitors of spliceosome

Arun K Ghosh  1 , Zhi-Hua Chen
Affiliations

Enantioselective syntheses of FR901464 and spliceostatin A: potent inhibitors of spliceosome

Arun K Ghosh et al. Org Lett. .

Abstract

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 A-tetrahydropyran ring was constructed from (R)-isopropylidene glyceraldehyde. The functionalized tetrahydropyran B-ring was synthesized utilizing a Corey-Bakshi-Shibata reduction, an Achmatowicz reaction, and a stereoselective Michael addition as the key steps. Coupling of A- and B-ring fragments was accomplished via cross-metathesis.

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Figures

Scheme 1
Scheme 1
Retrosynthesis of FR901464.
Scheme 2
Scheme 2
Synthesis of epoxy alcohol Segment 3
Scheme 3
Scheme 3
The synthesis of acid 7
Scheme 4
Scheme 4
Synthesis of Amide 4
Scheme 5
Scheme 5
Synthesis of FR901464
See this image and copyright information in PMC

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