Beyond the Diketopiperazine Family with Alternatively Bridged Brevianamide F Analogues

A method for the
preparation of 3,5-bridged piperazin-2-ones from
a tryptophan–proline-based diketopiperazine is described using
diphosgene to induce the ring closure. Density functional theory calculations
were conducted to study the mechanism of this C–C bond formation.
Several derivatives of the thus obtained α-chloroamine were
synthesized by substitution of the chlorine atom using a range of O-, N-, S-, and C-nucleophiles. This novel class of brevianamide F analogues
possess interesting breast cancer resistance protein inhibitory activity.