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 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.
Department of Chemistry and Department of Medicinal Chemistry, Purdue University , 560 Oval Drive, West Lafayette, Indiana 47907, United States.
Arun K
AK
Ghosh
Zhi-Hua
ZH
Chen
D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D017381:Spliceosomes / Q000737:chemistry / Q000187:drug effects*; D013237:Stereoisomerism
C104486:FR 901464; D011714:Pyrans; D013141:Spiro Compounds; C553684:spliceostatin A