Solid-Phase Biomimetic Synthesis of Polyketide

Abstract

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 13 C 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.

Iterative synthesis of nitrogen-containing polyketide via oxime intermediates

“…1 We have recently developed an iterative method for polyketide synthesis inspired by the biosynthetic mechanism. 2 In this method, chain elongation of carboxylic acid via decarboxylative dehydration condensation with malonic acid half thioester (MAHT) is iteratively performed to form polyketide precursors. The advantage of the above strategy is that a variety of structures can be constructed by a tailored method, and chemical modifications such as reduction or alkylation can be easily made to the intended positions.…”