Since their discovery in 2004,the pladienolides underwent rapid development and entry into clinical trials.Structurally based on a motif first discovered in FD-895, a related polyketideisolated in 1994 from an isolate of Streptomyceshygroscopicus, the potent activity and novel target (the spliceosome) ofthe pladienolides offered strong potential supporting the clinical trials. Whileclinical trials were recently suspended, interest in this unique family ofspliceosome inhibitors continues. Our studies have focused on generating second-generationclinical candidates by developing a detailed understanding of the pharmacologyof this family of natural products. We now describe the current progress in oursynthesis of a related natural product FD-895 and reflect on the currentinitiative to translate FD-895 into the clinic.

Synthetic studies on the FD-895 and pladienolide polyketides

241st National Meeting (2011)

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