Synthesis of proposed structure of aaptoline a, a marine sponge-derived 7,8-dihydroxyquinoline, and its neuroprotective properties in c. Elegans

Abstract

A concise and efficient synthesis of the proposed structure of aaptoline A, a 7,8-dihy-droxyquinoline derived from a marine sponge, was accomplished in seven steps with a 52% overall yield. A key feature of the synthesis is the high-yielding Ag(I)-catalyzed cycloisomerization of the N-propargylaniline precursor to afford the quinoline carboxylate skeleton from acid-labile methyl aminobenzoate. However, the spectral data of the synthesized aaptoline A were not consistent with those of previous studies. The structure of the synthesized aaptoline A was confirmed by combined 2D NMR analysis. Additional studies on the bioactivity of the synthesized aaptoline A revealed that it has the ability to protect dopaminergic neurons against MPP+-induced neurotoxicity in C. elegans. In addition, impaired food-sensing ability and travel distance capability in C. elegans were signifi-cantly ameliorated by aaptoline A treatment, suggesting that aaptoline A can protect dopaminergic neurons both morphologically and functionally.