Abstract:
In a survey of the secondary metabolite chemistry profiles of ten New Zealand, one
Antarctic and one South African-sourced collections of Latrunculia spp. sponges, eighteen
discorhabdin alkaloids have been isolated. Four of those, namely discorhabdin K,
3-dihydro discorhabdin A, 1-thiomethyl discorhabdin G*/I, and 16a,17a-dehydro
discorhabdin W were fully characterized as new natural products in the series. In addition,
for the first time, five enantiomeric pairs and two sets of diastereomers of the naturallyoccurring
discorhabdin alkaloids were identified. The absolute configuration of all of the
chiral compounds isolated, including new natural products, has been established upon
comparison of the observed experimental data with the results of time dependant density
functional theory calculations of the electronic circular dichroism spectra.
A structure activity relationship study on discorhabdin B, the main natural product of the
Wellington-sourced sponges, has identified four reactive centres on the molecule and
yielded nine novel semi-synthetic derivatives. Consequently, a new discorhabdin
biosynthetic tree was proposed which highlighted discorhabdin B as a crucial precursor to
a number of other naturally-occurring analogues. The importance of the iminoquinone
moiety and the spirodienone ring with respect to the bioactivity of the compounds in a
range of naturally-occurring discorhabdins was demonstrated. A new semi-synthetic
derivative, 1-discorhabdyl discorhabdin D, was identified as a potent anti-malarial agent
and has opened new possibilities for the therapeutic development of the discorhabdin
alkaloids.