2. Academic Validation
  3. Synthesis of 15-methylene-eburnamonine from (+)-vincamine, evaluation of anticancer activity, and investigation of mechanism of action by quantitative NMR

Synthesis of 15-methylene-eburnamonine from (+)-vincamine, evaluation of anticancer activity, and investigation of mechanism of action by quantitative NMR

  • Bioorg Med Chem Lett. 2013 Nov 1;23(21):5865-9. doi: 10.1016/j.bmcl.2013.08.095.
James R Woods 1,  Mark V Riofski,  Mary M Zheng,  Melissa A O'Banion,  Huaping Mo,  Julia Kirshner,  David A Colby
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, United States.
PMID: 24055047 DOI: 10.1016/j.bmcl.2013.08.095
Abstract

The biological role of installing a critical exocyclic enone into the structure of the alkaloid, (-)-eburnamonine, and characterization of the new chemical reactivity by quantitative NMR without using deuterated Solvents are described. This selective modification to a natural product imparts potent Anticancer activity as well as bestows chemical reactivity toward nucleophilic thiols, which was measured by quantitative NMR. The synthetic strategy provides an overall conversion of 40%. In the key synthetic step, a modified Peterson olefination was accomplished through the facile release of trifluoroacetate to create the requisite enone in the presence of substantial steric hindrance.

Keywords

Alkaloid; Anticancer agent; Covalent; Mechanism of action; NMR.

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