Total synthesis and biological evaluation of catenulobactin B as neuroprotective agent

The first total synthesis of catenulobactin B has been accomplished in longest linear eight steps (34% overall yield). The convergent route featured a molybdenum(VI) oxide-promoted dehydrative cyclization, a key double amide coupling strategy and a set of judicious functional group transformations. Biological evaluation revealed that catenulobactin B markedly inhibited α-synuclein aggregation and attenuated the progression of 6-OHDA-induced dopaminergic neurodegeneration in C. elegans. This neuroprotective effect may be closely associated with the modulation of iron metabolism-related gene expression. These findings identify catenulobactin B as a promising neuroprotective agent targeting iron homeostasis for Parkinson's disease-related neurodegeneration.