Biomimetically Inspired, One-Step Synthesis of Exotine A and Exotine B

The
one-step syntheses of exotine A and exotine B, which comprise
the unusual coumarin-cyclohepta­[b]­indole ring system,
have been achieved via the biomimetically inspired combination of
indole, prenal, and either trans-dehydroosthol or
gleinadiene. This facile three-component reaction delivered a mixture
(17:1) of exotine A and 11′-epi-exotine A
in a 43% yield from trans-dehydroosthol and a mixture
(4:1) of exotine B and 11′-epi-exotine B in
a 50% yield from gleinadiene. Some mechanistic aspects of this process
were explored, and spectral evidence for 3,3′-spiroindolenine
intermediates was obtained. Moreover, a skeletal isomer of exotine
A that likely originates from a 1,2-alkyl rearrangement of a protonated
3,3′-spiroindolenine was isolated and characterized by X-ray
crystallography. These findings not only provide experimental support
for Jiang’s proposed biosynthesis of exotine A and exotine
B but also foreshadow the existence of other exotine-derived natural
products having isomeric frameworks. Exploratory attempts to induce
an enantioselective 3CR using a chiral phosphoric acid were unsuccessful.