Site-Selective Functionalization of Linear Diterpenoids through U‑Shaped Folding in a Confined Artificial Cavity

Even
flexible linear substrates are conformationally fixed within
the hydrophobic confined cavities of enzymes. This enables preorganization
of the substrates and their positioning in close proximity to the
active center to facilitate stereo- and site-selective reactions.
Here, we demonstrate the site-selective electrophilic addition of
linear diterpenoids within a self-assembled coordination cage. The
reactions proceed through folding of the linear substrates into a
U-shaped conformation, which results in noncovalent protection of
internal CC bonds to enhance the site selectivity.