Total synthesis of natural products via conjugated ynone intermediates: a new millennium update

Natural products play a vital role in both medicinal chemistry and industrial chemistry due to their unique structural diversity, biological activity, and ability to serve as precursors for the development of therapeutic agents, materials, and chemicals. Drug discovery has always been influenced by natural compounds, which have served as the basis for many medicinal compounds. Ynones, or α,β-acetylenic ketones, are valuable intermediates in organic synthesis and have been used to prepare a variety of natural products and bioactive compounds due to their exceptional reactivity and adaptability. Ynones not only are integral to the biosynthesis of certain natural products but also serve as crucial building blocks in synthetic chemistry due to their ability to undergo various reactions, such as Michael addition and cycloaddition, which can lead to a wide array of structural motifs with diverse biological activities. These substances make it possible for atom-economical processes like cyclizations and rearrangements to produce intricate molecular structures with improved pharmacological characteristics. The synthetic methods developed using ynones from 2005 to 2024 are discussed in this review, with a focus on innovative and environmentally conscious methods of producing natural compounds. Their critical role in medicinal chemistry is highlighted through insights into developments and future directions.