The spliceosome, the cellular splicing machinery, regulates RNA splicing of messenger RNA precursors (pre-mRNAs) into maturation of protein coding RNAs. Recurrent mutations and copy number changes in genes encoding spliceosomal proteins and splicing regulatory factors have tumor promoting or suppressive functions in hematological malignancies, as well as some other cancers. Over the past 10 years, a list of natural products, including FD-895, pladienolide B, herboxidiene, and spliceostatin A, have been identified as spliceosome modulators. They have been shown to have anti-cancer effect in vitro and in vivo models. However, these compounds demonstrate poor metabolic stability and short half-lives in vivo, excluding them from entering clinical evaluation. This invention, 17S-FD-895, is an analog of FD-895 and was synthesized through the combination of total synthesis and synthetic methods, demonstrating improved stability and on-target effect. This new spliceosome targeting compound was evaluated in different secondary acute myeloid leukemia models and showed potent efficacy in inhibition of acute myeloid leukemia (AML) LSC and disruption of AML maintenance in vitro and in mouse xenograft models (Crews et al. 2016). The study by Crews et al. indicates the pivotal role of spliceosome in secondary acute myeloid leukemia and the therapeutic potential of targeting leukemia stem cells in this subtype of AML often unresponsive to current therapy.