Chemoselective purification technologies have seen great success in biomolecule isolation, with a classic example being the genetically-encoded His tag utilized to enrich desired proteins from a crude lysate. We sought to translate this purification tactic into a powerful tool for the isolation of natural products and demonstrate that chemoselective enrichment can reduce the number of purification steps required and increase the yield obtained for important natural products, as compared to the use of traditional chromatography methods alone. To date, we have reported reversible enrichment tags for three functional groups, carboxylic acids and aliphatic or aryl hydroxyls. To illustrate the power of chemoselectivity-mediated purification of natural products, we present here an improved isolation of borrelidin. Application of our carboxylic acid tag yielded pure borrelidin in only two steps and with double the yield acquired with traditional chromatography methods. These results highlight the utility of this orthogonal strategy to facilitate the isolation of natural products, which are often present in minute quantities in their source materials.