Building Chemical Probes Based on the Natural Products YM-254890 and FR900359: Advances toward Scalability

The biological activity of natural products YM-254890 (YM) and FR900359 (FR) has led to significant interest in both their synthesis and the construction of more simplified analogs. While the simplified analogs lose much of the potency of the natural products, they are of interest in their own right, and their synthesis has revealed synthetic barriers to the family of molecules that need to be addressed if a scalable synthesis of YM and FR analogs is to be constructed. In the work described here, a synthetic route to simplified analogs of YM is examined and strategies for circumventing some of the challenges inherent to constructing the molecules are forwarded.