Facilitating the Isolation of Polar Natural Products: Mild 1,1’‐Carbonyldiimidazole‐Enabled Method for Derivatization of Acids and Alcohols

Many secondary metabolites containing carboxylic acid and alcohol functional groups are highly polar and can be difficult to purify and isolate from complex extracts obtained from natural sources. The conversion of these natural products to their corresponding alkyl esters/ carbonates under mild conditions can simplify their purification and isolation. However, traditional derivatization methods have often relied on toxic and/ or corrosive reagents that can also lead to byproduct formation or epimerization in some instances. In this work, 1,1′‐carbonyldiimidazole (CDI), a relatively inexpensive reagent with inherently low toxicity, is utilized to activate polar natural products containing carboxylic acids and alcohols to enable the formation of less polar species (N‐acylimidazoles and N‐acyloxymidazoles). These intermediates are readily converted into methyl esters and carbonates by treatment with methanol. It is anticipated that this rather simple and versatile derivatization method can facilitate the efficient isolation of secondary metabolites bearing polar carboxylic acid and alcohol residues.