Development of a Cross‐Conjugated Vinylogous [4+2] Anionic Annulation and Application to the Total Synthesis of Natural Antibiotic (±)‐ABX

Abstract

The cross‐conjugated vinylogous [4+2] anionic annulation has been newly developed, the cascade process of which has a high preference for regiochemical control and chemoselectivity, giving rise to exclusively Michael‐type adducts in moderate to high yields (up to 94 %, 35 examples). By making use of this approach as a key operation, the first total synthesis of natural antibiotic ABX, in racemic form, has been successfully achieved in a concise 7‐step sequence with an overall yield of about 20 %.

Concise Chemoenzymatic Synthesis of Fasamycin A

“…7,8 Additionally, Shia has also reported the first synthesis of a related natural product, BE-24566B, also known as ABX. 9 Inspired by these chemical syntheses and the biosynthetic proposal, our retrosynthesis for 1 starts from disconnection of its C−Cl bond via a late stage enzymatic chlorination to reveal naphthacemycin B1 (3). Here, we envisioned an opportunity to functionally characterize the FDH (hereby termed FasV) from fasamycin biosynthesis for the first time and perform initial investigations into its biocatalytic utility (Scheme 1).…”

“…The medicinal potential and the unique framework of this natural product family have stimulated two elegant chemical syntheses by the groups of Shia and Kraus. , Additionally, Shia has also reported the first synthesis of a related natural product, BE-24566B, also known as ABX . Inspired by these chemical syntheses and the biosynthetic proposal, our retrosynthesis for 1 starts from disconnection of its C–Cl bond via a late stage enzymatic chlorination to reveal naphthacemycin B1 ( 3 ).…”