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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Woods, James R.¹  Riofski, Mark V.¹  Zheng, Mary M.²  O'Banion, Melissa A.²  Mo, Huaping^1,3  Kirshner, Julia²  Colby, David A.^1,4 

[1] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA

[2] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA

[3] Purdue Univ, Interdept NMR Facil, W Lafayette, IN 47907 USA

[4] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA

关键词: Alkaloid;    Anticancer agent;    NMR;    Covalent;    Mechanism of action;   

DOI  :  10.1016/j.bmcl.2013.08.095

来源: Elsevier

【 摘 要 】

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. (C) 2013 Elsevier Ltd. All rights reserved.

【 授权许可】

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