The Abiotic Oxidation of Organic Acids to Malonate

The nucleophilicity of the alpha-carbon of malonate, coupled with its potential for subsequent decarboxylation, makes it an intriguing building block in prebiotic chemical scenarios. In this work, a variety of citric acid cycle (TCA) intermediates is shown to unexpectedly generate malonate in an oxidizing environment. The reactions are facile in aqueous solution containing hydrogen peroxide, a prevalent abiotic oxidant. In modern metabolism, malonate is a carbon source for acetylCoA. Additionally, its thioester is the substrate for the biosynthesis of both fatty acids and polyketides. The data presented herein may hint at how an early link was formed between polyketide, fatty acid, and TCA pathways.