Research Grants Program Office (RGPO)
Enantioselective Synthesis of a Cyclopropane Derivative of Spliceostatin A and Evaluation of Bioactivity.
- Author(s): Ghosh, Arun K
- Reddy, Guddeti Chandrashekar
- Kovela, Satish
- Relitti, Nicola
- Urabe, Veronica K
- Prichard, Beth E
- Jurica, Melissa S
- et al.
Published Web Locationhttps://doi.org/10.1021/acs.orglett.8b03228
Spliceostatin A is a potent inhibitor of spliceosomes and exhibits excellent anticancer activity against multiple human cancer cell lines. We describe here the design and synthesis of a stable cyclopropane derivative of spliceostatin A. The synthesis involved a cross-metathesis or a Suzuki cross-coupling reaction as the key step. The functionalized epoxy alcohol ring was constructed from commercially available optically active tri- O-acetyl-d-glucal. The biological properties of the cyclopropyl derivative revealed that it is active in human cells and inhibits splicing in vitro comparable to spliceostatin A.