Total Synthesis of GEX1Q1, Assignment of C‑5 Stereoconfiguration and Evaluation of Spliceosome Inhibitory Activity

An enantioselective total synthesis of GEX1Q1 has been accomplished in a convergent manner. The C-5 asymmetric center has now been assigned through synthesis. GEX1Q1 displayed slightly better spliceosome inhibitory activity over its C-5 epimer. The salient features of this synthesis include an asymmetric hetero-Diels–Alder reaction to construct the tetrahydropyran ring and a Suzuki cross-coupling to assemble the key segments

Enantioselective Synthesis of Spliceostatin E and Evaluation of Biological Activity

An enantioselective total synthesis of spliceostatin E has been accomplished. The δ-lactone unit A was constructed from readily available (<i>R</i>)-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 <i>B</i>-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