Synthesis of the C1–C23 Fragment of the Archazolids and Evidence for V-ATPase but not COX Inhibitory Activity

Gregory O’Neil describes the synthesis of the C1–C23 fragment of the archazolids.

V-ATPase is an important anti-cancer target and archazolid natural products represent a promising starting point for the development of V-ATPase-based cancer therapies. Over the last few years, the intensity of cancer research involving archazolid natural products has increased, as evidenced by several recent studies demonstrating promising activity for these compounds against particularly lethal and aggressive types of cancer. This follows an increasing appreciation for the role of the vacuolar-type ATPase (V-ATPase) in cancer. However, archazolids remain scarcely available, which has hindered their development as V-ATPase inhibitor therapeutics. Recently, Professor Gregory O’Neil’s group described what promises to be a highly efficient synthesis of the archazolids based on a convergent Stille coupling to construct the substituted Z,Z,E-conjugated triene unique to this class of compounds.

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