Lasonolide A: synthetic explorations Public Deposited

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Last Modified
  • March 21, 2019
Creator
  • Milner, Erin Elizabeth Barthelme
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • First isolated in 1984 from the marine sponge Forcepia trilabis, lasonolide A was found to inhibit A-549 human lung carcinoma cells and P-388 murine leukemia cell lines among others. This cytotoxic natural product was chosen because of its biological activity and challenging polyketide structure. Interesting structural features include two cis-2,6-substituted tetrahydropyran rings integrated into the highly unsaturated macrolide structure, and a quaternary stereogenic center at C22. Construction of the A-ring showcases a novel zinc triflate-mediated asymmetric alkynylzinc addition hetero-Michael reaction, which was developed to selectively form the 2,6-cis tetrahydropyran motif. To assemble the B-ring, alternate carbon nucleophiles were explored to displace the N-acyl thioimide auxiliary and prepare beta-ketonitrile and beta-ketoester moieties. Coupling of the three fragments via olefination, esterification, and metathesis strategies is also outlined.
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  • In Copyright
Advisor
  • Crimmins, Michael T.
Degree granting institution
  • University of North Carolina at Chapel Hill
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  • Open access
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