The aggregation of the neuronal protein α-synuclein (α-syn) is intrinsically linked to the development and progression of Parkinson's disease (PD). Recently we screened the MeOH extracts from 283 marine invertebrates for α-syn binding activity using an affinity mass spectrometry (MS) binding assay and found that the extract of the ascidian <i>Polycarpa procera</i> displayed activity. A subsequent bioassay-guided purification led to the isolation of one new α-syn aggregation inhibitory butenolide procerolide E (<b>3</b>) and one new α-syn aggregation inhibitory diphenylbutyrate methyl procerolate A (<b>5</b>). Herein we report the structure elucidation of procerolide E (<b>3</b>) and methylprocerolate A (<b>5</b>) and α-syn aggregation inhibitory activity of procerolides C-E (<b>1</b>-<b>3</b>), methyl procerolate A (<b>5</b>) and procerone A (<b>4</b>). We also report the α-syn binding activity of 3-bromo-4-methoxyphenylacetamide (<b>6</b>) and a synthetic butenolide library, which has allowed us to determine α-syn aggregation inhibitory structure-activity relationships for this class of compounds.