Semisynthetic Studies Establish a Role for Conjugate Halide Exchange in the Formation of Chlorinated Pyrroloiminoquinones and Related Alkaloids

Two novel pyrroloiminoquinone alkaloids, 6-chlorodamirone
A and
6-bromodamirone A, have been identified for the first time from the
marine sponge Latrunculia sp. (order: Poecilosclerida:
family Latrunculiidae), sourced from Western Australia. Alongside
these new compounds, seven previously known metabolites were also
isolated. Despite being obtained in submilligram quantities, the structures
of these natural products were successfully elucidated using high-resolution
mass spectrometry and nuclear magnetic resonance spectroscopy. To
confirm the structures of these newly discovered alkaloids, a semisynthetic
approach was employed starting from the more abundant metabolite,
damirone A, additionally, single crystal X-ray crystallography was
used to validate our structural proposals. The semisynthetic studies
suggest that the chlorinated alkaloids are likely formed through a
nonenzymatic conjugate halide substitution reaction rather than an
enzymatic process. This reactivity parallels that observed in related
metabolites, such as the caulibugulones B and C. Furthermore, a biomimetic
cascade reaction was attempted to synthesize the spirodienone moiety
characteristic of the discorhabdin alkaloids, inspired by the nucleophilic
substitution observed in the tricyclic damirone A system. Albeit unsuccessful,
these findings provide valuable insight into the reactivity of halogenated
pyrroloiminoquinones under various conditions.