Molecules (Oct 2021)

Synthesis of Proposed Structure of Aaptoline A, a Marine Sponge-Derived 7,8-Dihydroxyquinoline, and Its Neuroprotective Properties in <i>C. elegans</i>

  • Soobin Kim,
  • Wooin Yang,
  • Dong Seok Cha,
  • Young Taek Han

DOI
https://doi.org/10.3390/molecules26195964
Journal volume & issue
Vol. 26, no. 19
p. 5964

Abstract

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A concise and efficient synthesis of the proposed structure of aaptoline A, a 7,8-dihydroxyquinoline 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 significantly ameliorated by aaptoline A treatment, suggesting that aaptoline A can protect dopaminergic neurons both morphologically and functionally.

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