Derivatives of ?-Phenylisoserine Side Chain of Paclitaxel (Taxol) with Varying Hydrophobicity

Paclitaxel (Taxol) displays anticancer activity by binding to ?-tubulin and interrupting the cell cycle at the G2-M phase. It is known from previous studies that the Paclitaxel-binding pocket of ?-tubulin is very hydrophobic in nature. Structure-activity studies have shown that ?-phenylisoserine side chain at C-13 of Paclitaxel is essential for anticancer activity. We set out to develop structural analogues of ?-phenylisoserine with varying hydrophobicity using co-catalyzed oxidation and microwave mediated ring-opening strategies. It is expected that an increase in the hydrophobicity of ?-phenylisoserine side chain can increase the binding of Paclitaxel derivatives to ?-tubulin and thus increase the potency of these compounds as anti-cancer drugs.