Enantioselective Synthesis of Spliceostatin E and Evaluation of Biological Activity

ABSTRACT: An enantioselective total synthesis of spliceostatin E has been accomplished. The δ-lactone unit A was constructed from readily available (R)-glycidyl alcohol using a ring-closing olefin metathesis as the key reaction. A cross-metathesis of ring A containing δ-lactone and the functionalized tetrahydropyran B-ring provided spliceostatin E. Our biological evaluation of synthetic spliceostatin E revealed that it does not inhibit splicing in vitro and does not impact speckle morphology in cells. Spliceostatin E was reported to possess potent antitumor activity. Splicing is an essential step in gene expression in which noncoding sequences (introns) are removed from RNA transcripts and coding sequences (exons) are ligated to form messenger RNA (mRNAs).1 A complex ribonucleoprotein machinery, known as spliceosome, facilitates this splicing event.2 The splicing levels are generally increased in cancer cells, and as a consequence, spliceosome inhibitors have bee