Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Azazoindole alkaloid and its preparation and antimalarial use

A technology of indoles and alkaloids, applied in the fields of medicinal chemistry and pharmacology, can solve the problems of synthetic methods without chiral selectivity and non-stereoselective PS methods, etc.

Active Publication Date: 2020-06-19
ZHEJIANG UNIV
View PDF9 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The synthesis methods of azazoindole compounds have been reported in the literature, but most of the synthesis methods have no chiral selectivity, including a PS method without stereoselectivity

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Azazoindole alkaloid and its preparation and antimalarial use
  • Azazoindole alkaloid and its preparation and antimalarial use
  • Azazoindole alkaloid and its preparation and antimalarial use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Embodiment 1: Preparation of azazoindole isososidine (IV)

[0022] Dissolve compound II (0.4g, 2.5mmol) and compound III (1.1g, 2.5mmol) in KPi (50mM, pH=7.0, 200ml) respectively, add STR1 5mg, and incubate at 26°C for 12h. After the reaction is complete, no After purification, it was directly used in the reaction of Example 2.

Embodiment 2

[0023] Example 2: (10S, 11R, 11aS, 12aR)-10-(((2S, 3R, 4S, 5S, 6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H -pyran-2-yl)oxy)-11-ethenyl 10,11,11a,12,12a,14 hexahydro-4H-pyrano[4″,3″:4′,5′]pyrido Preparation of [1',2': 1,2]aza[3,4,5-cd]indol-7(5H)-ones (V).

[0024] Add 5% sodium carbonate solution (500ml) to the reaction solution of Example 1 and mix to obtain a suspension, and react at 70°C for 2 hours. After the reaction is completed, the solvent is removed by distillation under reduced pressure, and flash column chromatography obtains a yellow solid 4 , 14g, yield 86%. 1 HNMR (500MHz, CD 3 OD): δ7.35 (1H, d, J = 2.0Hz), 7.21 (1H, d, J = 8.0Hz), 7.18 (1H, d, J = 1.5Hz), 7.03 (1H, t, J = 8.0 Hz),6.84(1H,d,J=8.0Hz),5.64(1H,dt,J=17.0,10.0Hz),5.39(1H,d,J=2.0Hz),5.36(1H,dd,J=17.0 ,2.0Hz),5.29(1H,dd,J=10.0,2.0Hz),4.98(1H,d,J=5.0Hz),4.76(1H,dt,J=13.5,3.5Hz),4.58(1H,d ,J=8.0Hz),3.86(1H,dd,J=12.0,2.0Hz),3.64(1H,dd,J=12.0,6.0Hz),3.49(1H,m),3.07-3.26(6H,m) ,2.97(1H,ddd,J=8...

Embodiment 3

[0025] Example 3: Preparation of reduced azaindole lactamized isosidine (VI)

[0026] Compound V (3.00g, 6.00mmol) was dissolved in 50ml of methanol, 10% palladium carbon (300mg) was added to react overnight at room temperature, the palladium carbon was removed by filtration, and the solvent was distilled off under reduced pressure to obtain 2.98g of a yellow solid with a yield of 98% .

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides anazepineindole alkaloid and a preparation method and an anti-malarial application thereof.The preparation method utilizes tryptamine and split ring strychnine as initial raw materials to obtain two diastereoisomers after being catalyzed and chemically modified by strictosidinesynthetase and phosphoric acid.According to the method, two diastereoisomers of the azepineindole alkaloid are synthesized through a simple enzymatic chemical reaction and a purification method, a research shows that compounds and pharmaceutical salts thereof have outstanding anti-malarial activityand can be applied to the preparation of anti-malarial drugs.The structural formula of the two compounds is shown in the description.

Description

[0001] field of invention [0002] The invention belongs to the field of medicinal chemistry and pharmacology, and relates to the preparation of azazoindole alkaloids and enzymatic chemical method, and the application of the compounds in the preparation of antimalarial drugs. [0003] Background of the invention [0004] The asymmetric Pictet-Spengler (PS) reaction is one of the important methods to construct indole alkaloids with chiral centers, but the asymmetry often relies on complex structures, high prices, and ligand-bound metal catalysts. Strictosidine Synthase (STR1) is an enzyme that can catalyze the Pictet-Spengler (PS) reaction, and is also one of the important enzymes in the biosynthesis of monoterpene indole alkaloids in higher plants. , high selectivity and so on. Despite the multiple advantages of the enzymatic chemistry of STR1, its strict substrate adaptability requirement limits its application in the biomimetic synthesis of monoterpene indole alkaloids. Exp...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D487/22A61P33/06
Inventor 邹宏斌蔡云瑞邵娜娜
Owner ZHEJIANG UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com