4880-88-0

Usage

Uses

Used in Pharmaceutical Industry:
(-)-Eburnamonine is used as a cerebral vasodilatator for improving blood flow to the brain and potentially treating conditions related to reduced cerebral blood flow.
Used in Emergency Medicine:
(-)-Eburnamonine is used as a protective agent for mice from the lethal consequences of hypoxia, indicating its potential use in emergency medicine to treat patients suffering from oxygen deprivation or related conditions.
Used in Research:
(-)-Eburnamonine's unique chemical properties and biological activities make it a valuable compound for research purposes, particularly in the fields of neuroscience, pharmacology, and toxicology. It can be used to study the effects of various substances on the central nervous system and to develop new therapeutic strategies for neurological disorders.

Originator

Euburnamonine ,Shanghai Lansheng Corporation

Manufacturing Process

200 g (0.087 moles) of cis-1-ethyl-1-(2'-hydroxy-2'-carboxyethyl)- 1,2,3,4,6,7,12,12b-octahydro-indolo[2,3-a]quinolizine were suspended in 100 ml of xylene. 12 g of supported silver carbonate (a silver carbonate-Celite reagent, containing 50% of silver carbonate) were added to the suspension, and the system was boiled for 8 hours under a nitrogen atmosphere, with constant stirring. Thereafter the hot solution was filtered, washed with 3 x 30 ml to 5% sodium carbonate solution, dried over magnesium sulfate, and evaporated under reduced pressure. 1.05 g of a solid residue, which was a mixture of racemic vincamone and racemic vincanol, was obtained. 40 ml of ethyl ether were added to the mixture, and the insoluble crystals were filtered off. The crystals were recrystallized from methanol, to yield 0.5 g of (+/-)- eburnamonine (vincamone). Yield: 29.5%. MP: 201°-202°C. The value was identical with the literature value (J. Mokry et aI.: CoII. Czech, Chem. Comm. 28, 1309, 1963). The etheral mother liquor was processed by preparative layer chromatography (adsorbent: Kieselgel PF 254+366 , developing agent: a 14:2 mixture of benzene and methanol). The obtained substance was recrystallized from ether to yield 0.2 g (16%) of (+/-)-vincanol (eburnamine). MP: 163-164°C, under decomposition. The IR spectrum of the obtained substance was identical with that of the authentic sample.Resolution of (+/-)-vincamone:10.0 g (0.0342 moles) of (+/-)-vincamone and 12.2 g (0.0342 moles) of (-)- dibenzoyl tartaric acid were dissolved in 150 ml of dichloromethane, the solution was seeded with crystalline (-)-vincamone-(-)-dibenzoyl-tartarate, and the mixture was left to stand. The separated crystals were filtered off, dissolved in dimethylformamide, and the pH of the solution was adjusted to 9 with aqueous ammonia. The separated substance was filtered off, washed with water, and dried. This way 4.2 g (84%) of (-)-vincamone were obtained; MP: -176°C; α D 20 = -96°. The mother liquor of resolution was evaporated and (+)- vincamone was separeted as described above. The obtained substance had MP: 173°-176°C.; α D 20 = +96°.

Therapeutic Function

Cerebrotonic

InChI:InChI=1/C19H22N2O/c1-2-19-9-5-10-20-11-8-14-13-6-3-4-7-15(13)21(16(22)12-19)17(14)18(19)20/h3-4,6-7,18H,2,5,8-12H2,1H3/p+1/t18-,19+/m1/s1

Upstream product

• 113883-29-7 C₂₂H₂₆N₂OS₂ 
• 113883-26-4 eburnamonine-17α-xanthogenate 
• 473-99-4 14,15-dihydroeburnamenin-14-ol 
• 19877-90-8 (15S,17S,19S)-15-ethyl-1,11-diazapentacyclo[9.6.2.0^2,7.0^8,18.0^15,19]nonadeca-2,4,6,8⁽¹⁸⁾-tetraen-17-ol 
• 66113-74-4 hydroxy-16 dehydro-1 vincadifformine 
• 473-99-4 eburnamine 
• 42971-09-5 Vinpocetine 
• 393563-08-1 (4R,5S)-3[(2R)-2-((1R*)-1-hydroxyethyl)-1-oxo-4-pentenyl]-4-methyl-5-phenyl-2-oxazolidinone 
• 393563-17-2 (4S)-N-[2-(3-indolyl)ethyl]-4-ethyl-4-(2-tert-butyldiphenylsiloxyethyl)-5-oxopentamide 
• 262847-04-1 (5S)-N-[2-(3-indolyl)ethyl]-5-ethyl-5-(2-tert-butyldiphenylsiloxyethyl)-6-hydroxy-δ-lactam 
• 111687-25-3 (1S,12bR)-1-ethyl-1-(2-hydroxyethyl)-4-oxo-2,3,6,7,12,12b-hexahydro-1H-indolo[2,3-a]quinolizine 
• 62926-55-0 (1S,12bS)-1-[1,3]Dithian-2-ylmethyl-1-ethyl-1,2,3,4,6,7,12,12b-octahydro-indolo[2,3-a]quinolizine 
• 38199-30-3 Δ¹⁴-vincamenine 
• 86667-27-8 (-)-(1,2,3,4,6,7,12,12bα-octahydro-indolo<2,3-a>quinolizin-1β-yl)-pyruvic acid oxime 

Downstream Products

• 101242-46-0 (6S)-6-hydroxyeburnamonine 
• 101242-46-0 (6R)-6-hydroxyeburnamonine 
• 473-99-4 eburnamine 
• 19877-90-8 (15S,17S,19S)-15-ethyl-1,11-diazapentacyclo[9.6.2.0^2,7.0^8,18.0^15,19]nonadeca-2,4,6,8⁽¹⁸⁾-tetraen-17-ol 
• 19877-89-5 (-)-isoeburnamine 
• 1617-90-9 vincamin 
• 65026-49-5 (15S,19S)-15-ethyl-1,11-diazapentacyclo[9.6.2.0^2,7.0^8,18.0^15,19]nonadeca-2,4,6,8⁽¹⁸⁾-tetraene 

Relevant academic research and scientific papers

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

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.

NITROINDOLENINES EN SERIE VINCADIFFORMINE : INTERMEDIAIRES D'ACCES A LA VINCAMONE ET A UN SQUELETTE AZAHOMOASPIDOSPERMANE

Vincadifformine and its 10-substituted analogs give in good yields 16-nitro indolenines of which the reactivity has been studied. By a two step process (demethoxycarbonylation and chloration on C16) nitro-indolenine 2b leads to gem-chloro-nitro 6.By an other two step sequence (NaBH3CN, NaH) nitro-indolenine 2c yields compound 10 via a 16 -> 1 COOCH3 migration.By heating compounds 6 and 10 in CF3COOH, rearranged products are obtained : vincamone 5 from 6 and azahomoaspidospermane 13 from 18.Mechanisms of formation of 5, 10 and 13 are discussed.

Intermediate, preparation method and application of intermediate in synthesis of vincamine

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.

Intermediate and preparation method and application thereof in synthesis of vinorchine

The invention relates to the technical field of chemical drug synthesis, and discloses an application of an intermediate or a preparation method thereof in synthesis of vinorchin, adopts a modular synthetic strategy, adopts the compound D with 1 ring structures and C20 quaternary carbon centers, 5 (i.e. the compound 5) as a synthesis building block. The operation is simple and reaction conditions are easy for large-scale amplification effect.

The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16′-epi-Leucophyllidine

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.

Catalytic Asymmetric Alkynylation of 3,4-Dihydro-β-carbolinium Ions Enables Collective Total Syntheses of Indole Alkaloids

Chiral tetrahydro-β-carboline (THβC) is not only a prevailing structural feature of many natural alkaloids but also a versatile synthetic precursor for a vast array of monoterpenoid indole alkaloids. Asymmetric synthesis of C1-alkynyl THβCs remains rarely explored and challenging. Herein, we describe the development of two complementary approaches for the catalytic asymmetric alkynylation of 3,4-dihydro-β-carbolinium ions with up to 96 % yield and 99 % ee. The utility of chiral C1-alkynyl THβCs was demonstrated by the collective total syntheses of seven indole alkaloids: harmicine, eburnamonine, desethyleburnamonine, larutensine, geissoschizol, geissochizine, and akuammicine.

Preventing Morphine-Seeking Behavior through the Re-Engineering of Vincamine's Biological Activity

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.

ANALOGS OF VINCAMINE AND USES THEREOF

The present disclosure provides compounds of any one of Formulae (I'), (I), (IA), (II'), (II), (IIA), (IIIA), (III"), (III'), (III), (IIIA), (IV), (V'), (V), (VI), (VII), (VIII'), (VIII), (ΙΧ'), (IX), and (X). The compounds described herein may be useful in treating and/or preventing a broad range of diseases (e.g., proliferative disease (e.g., cancers (e.g., non-small cell lung cancer, or glioma), inflammatory diseases, autoimmune diseases), CNS disorder (e.g., drug addiction), metabolic disorder (e.g., diabetes), or infectious disease (e.g., bacterial infection or parasitic infection (e.g., malaria))). Also provided in the present disclosure are pharmaceutical compositions, methods of synthesis of a compound described herein, kits, methods, and uses including or using a compound described herein.

Asymmetric Total Synthesis of Eburnamine and Eucophylline: A Biomimetic Attempt for the Total Synthesis of Leucophyllidine

The first enantiospecific total synthesis of (+)-6 has been achieved employing a Friedl?nder quinoline synthesis as a key step. Asymmetric synthesis of the architecturally complex eburnamine 5 has also been accomplished utilizing an intramolecular acid-mediated cyclization of a carbinol amine lactone moiety. Highlights of the effective modular synthetic strategy include development of the common precursor 4 for the construction of the privileged scaffolds 5 and 6 with an all-carbon quaternary stereocenter utilizing a Johnson-Claisen rearrangement strategy. Attempts have been made to synthesize 1 by the biomimetic coupling of 5 and (+)-6; however, regioisomeric 26 was formed.

A Radical Cascade Enabling Collective Syntheses of Natural Products

Natural products have long been important inspirations for the development of chemical methodologies, theories, and technologies, and ultimately, discoveries of new drugs and materials. Chemical syntheses have traditionally yielded individual or small groups of natural products; however, methodology development allowing the synthesis of a large collection of natural products remains scarce. Here, we report an efficient photocatalytic radical cascade method that enables access to libraries of chiral and multiple-ring-fused tetrahydrocarbolinones. The radical cascade can controllably introduce complexity and functionality into products with excellent chemo-, regio-, and diastereoselectivity. The power of this distinct method has been demonstrated by the efficient syntheses of 33 monoterpenoid indole alkaloids belonging to four families.