Synthetic Studies on the Initially Proposed Structure of Protoaculeine B: Discovery of Neuronally Active Heterotricyclic Amino Acids

Herein, we report our results on the synthetic studies of the originally proposed structure of protoaculeine B, isolated from a marine sponge. Starting from tryptophan, two candidates of the suitably protected heterotricyclic subunits were stereoselectively synthesized over 8 and 16 steps, respectively. Furthermore, two diastereomeric heterotricyclic amino acids, finally synthesized, were found to be neuroactive: the (9S*,11S*)-isomer with natural-type configuration was hyperactive, whereas diastereomeric (9S*,11R*)-isomer was hypoactive upon mice intracerebroventricular injection.

Automated summary

In this study, we report on the synthetic studies of protoaculeine B, originally proposed structure, isolated from a marine sponge. Starting from tryptophan, two candidates of suitably protected heterotricyclic subunits were synthesized over 8 and 16 steps, respectively. Furthermore, two diastereomeric heterotricyclic amino acids, finally synthesized, were found to have neuroactive properties, with the natural-type configuration being hyperactive and the diastereomeric configuration being hypoactive upon mice intracerebroventricular injection.