4880-88-0Relevant articles and documents
Synthesis of 15-methylene-eburnamonine from (+)-vincamine, evaluation of anticancer activity, and investigation of mechanism of action by quantitative NMR
Woods, James R.,Riofski, Mark V.,Zheng, Mary M.,O'Banion, Melissa A.,Mo, Huaping,Kirshner, Julia,Colby, David A.
, p. 5865 - 5869 (2013)
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.
Intermediate, preparation method and application of intermediate in synthesis of vincamine
-
Paragraph 0139-0143, (2021/09/01)
The invention relates to the technical field of chemical drug synthesis, and discloses an intermediate, a preparation method and application of the intermediate in synthesis of vincamine. A modular synthesis strategy is adopted, and a compound 1 with a D ring structure and a C20 quaternary carbon center and a tryptophol derivative 7 (namely the compound 7) with an indole ring are adopted as synthesis blocks for synthesis. The synthesis method is efficient; each step of the synthesis route is simple in reaction; the used reagent and solvent are cheap and easy to obtain; the operation is simple and convenient; the yield is high; and large-scale production is easy.
The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16′-epi-Leucophyllidine
Hayashida, Kohei,Korch, Katerina M.,Ngamnithiporn, Aurapat,Reimann, Christopher E.,Saito, Daisuke,Stoltz, Brian M.
supporting information, p. 17957 - 17962 (2021/07/12)
A synthetic approach to the heterodimeric bisindole alkaloid leucophyllidine is disclosed herein. An enantioenriched lactam building block, synthesized through palladium-catalyzed asymmetric allylic alkylation, served as the precursor to both hemispheres. The eburnamonine-derived fragment was synthesized through a Bischler–Napieralski/hydrogenation approach, while the eucophylline-derived fragment was synthesized by Friedl?nder quinoline synthesis and two sequential C?H functionalization steps. A convergent Stille coupling and phenol-directed hydrogenation united the two monomeric fragments to afford 16′-epi-leucophyllidine in 21 steps from commercial material.
Preventing Morphine-Seeking Behavior through the Re-Engineering of Vincamine's Biological Activity
Norwood, Verrill M.,Brice-Tutt, Ariana C.,Eans, Shainnel O.,Stacy, Heather M.,Shi, Guqin,Ratnayake, Ranjala,Rocca, James R.,Abboud, Khalil A.,Li, Chenglong,Luesch, Hendrik,McLaughlin, Jay P.,Huigens, Robert W.
, p. 5119 - 5138 (2020/06/10)
Innovative discovery strategies are essential to address the ongoing opioid epidemic in the United States. Misuse of prescription and illegal opioids (e.g., morphine, heroin) has led to major problems with addiction and overdose. We used vincamine, an indole alkaloid, as a synthetic starting point for dramatic structural alterations of its complex, fused ring system to synthesize 80 diverse compounds with intricate molecular architectures. A select series of vincamine-derived compounds were screened for both agonistic and antagonistic activities against a panel of 168 G protein-coupled receptor (GPCR) drug targets. Although vincamine was without an effect, the novel compound 4 (V2a) demonstrated antagonistic activities against hypocretin (orexin) receptor 2. When advanced to animal studies, 4 (V2a) significantly prevented acute morphine-conditioned place preference (CPP) and stress-induced reinstatement of extinguished morphine-CPP in mouse models of opioid reward and relapse. These results demonstrate that the ring distortion of vincamine offers a promising way to explore new chemical space of relevance to opioid addiction.
