Synthesis and kinase inhibitory activity of 3′-(S)-epi-K-252a

The 3′-epi diastereomer of K-252a was synthesized with the goal of evaluating the stereochemical requirements of the 3′-sugar alcohol on kinase inhibitory activity. Inverting the 3′-alcohol resulted in a 20 nM inhibitor of VEGFR2 and a 1 nM inhibitor of TrkA tyrosine kinase.