Discovery of the Nonenzymatic Formation of 3,3′-Spirooxindole γ-Butyrolactones Enables One-Step Construction of the Core Skeleton

Abstract 3,3′-Spirooxindole γ-butyrolactones are a small but intriguing family of natural products with diverse bioactivities and unique biosynthetic origins. Herein, we demonstrate that this core skeleton can form spontaneously via a nonenzymatic aldol condensation–lactonization cascade between 2-oxindole-3-acetic acid and aldehydes under mild conditions. Inspired by this biosynthetic insight, we developed an efficient method for the construction of the 3,3′-spirooxindole γ-butyrolactone scaffold, enabling the collective synthesis of seven natural products and broad structural diversification.