Balancing the efficacy vs. the toxicity of promiscuous natural products: Paclitaxel-based acid-labile lipophilic prodrugs as promising chemotherapeutics
In solid-phase organic synthesis, Wang resin is traditionally used for the immobilization of acids, alcohols, phenols, and amines. We report the use of Wang resin for the traceless synthesis of ketones via acid-labile enol ethers. We demonstrate the practicality of this synthetic strategy on the solid-phase synthesis of pyrrolidine-2,4-diones, which represent the core structure of several natural products, including tetramic acid. Base-triggered condensation of pyrrolidine-2,4-diones yielded 4-hydroxy-1,1′,2′,5-tetrahydro-2H,5′H-[3,3′-bipyrrole]-2,5′-diones.
Traceless Solid-Phase Synthesis of Ketones via Acid-Labile Enol Ethers: Application in the Synthesis of Natural Products and Derivatives