Synthesis of 15-methylene-eburnamonine from (+)-vincamine,evaluation of anticancer activity,and investigation of mechanism of action by quantitative NMR |
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| Authors: | James R. Woods Mark V. Riofski Mary M. Zheng Melissa A. O’Banion Huaping Mo Julia Kirshner David A. Colby |
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| Affiliation: | 1. Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, United States;2. Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, United States;3. Interdepartmental NMR Facility, Purdue University, West Lafayette, IN 47907, United States;4. Department of Chemistry, Purdue University, West Lafayette, IN 47907, United States |
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| 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. |
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| Keywords: | Alkaloid Anticancer agent NMR Covalent Mechanism of action |
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