Solid-Phase Biomimetic Synthesis of Polyketide

Solid-phase biomimetic polyketide synthesis has been developed. This method is composed of (i) carbon chain elongation of resin-bound carboxylic acid via decarboxylative Claisen condensation with malonic acid half thioester, (ii) stepwise transformation of the resulting β-ketothioester, and (iii) hydrolysis of thioester to regenerate the carboxylic acid for the next iteration cycle. Colorimetric tests were available for convenient monitoring of the solid-phase reactions; malachite green (basic dye) and iron(III) chloride successfully detected the carboxylic acid and the β-ketothioester, respectively. In addition, gel-phase ¹³C NMR could be utilized to confirm the progress of substrate immobilization. The established method was applied to the synthesis of the natural products, xylapyrone C and kavain. The present method could be further extended to the synthesis of (R)-kavain with catalytic diastereoselective asymmetric transfer hydrogenation as a key step.