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

Asymmetric synthesis method for pyrroline derivative with spirane structure

A synthetic method and technology of spiro ring structure, applied in the field of asymmetric synthesis of pyrroline derivatives, achieving high stereoselectivity, simple operation and high yield

Inactive Publication Date: 2020-01-14
CHONGQING UNIV
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there are a few reports on the reaction of aurone and methyleneamine ylides to construct spirocyclic pyrrolidine derivatives, there are no examples of the reaction of this type of compound with important physiological activities and isocyanoacetate compounds to construct spirocyclic pyrroline derivatives. see the report

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
  • Asymmetric synthesis method for pyrroline derivative with spirane structure
  • Asymmetric synthesis method for pyrroline derivative with spirane structure
  • Asymmetric synthesis method for pyrroline derivative with spirane structure

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Preparation of compound 3a

[0031]

[0032] step:

[0033]

[0034] Accurately weigh Ligand 1 (6.1 mg, 0.01 mmol) and silver acetate (0.83 mg, 0.005 mmol) into a 10 mL reaction tube equipped with a stirrer, add 2 mL of dichloromethane and stir at 25°C for 5 minutes. Then isocyanoacetate 2a (22.68mg, 0.12mmol) and starting material 1a (22.2mg, 0.1mmol) were added and reacted at 25°C, monitored by TLC until the reaction of starting material 1a was complete. The reaction solution was directly concentrated, and separated and purified by column chromatography to obtain 34.9 mg of product 3a with a yield of 85%.

[0035] White solid, melting point 58-59℃, R f =0.2 (petroleum ether: ethyl acetate = 3:2). 1 H NMR (400MHz, Chloroform-d) δ7.68(s,1H),7.65–7.60(m,2H),7.38(dd,J=6.5,3.1Hz,2H),7.29–7.16(m,9H), 7.09(t, J=7.5Hz, 1H), 4.01(s, 1H), 3.62(s, 3H), 3.08(d, J=13.4Hz, 1H), 2.97(d, J=13.4Hz, 1H); 13 C NMR(101MHz,Chloroform-d)δ197.14,172.04,171.39,160.38,138.79,135.82...

Embodiment 2

[0038] Preparation of compound 3b

[0039]

[0040] step:

[0041]

[0042]Ligand 2 (12.3mg, 0.02mmol) and silver oxide (2.3mg, 0.01mmol) were accurately weighed and placed in a 10mL reaction test tube equipped with a stirring bar, 1mL of tetrahydrofuran was added and stirred at 0°C for 5 minutes. Then isocyanoacetate 2a (22.68mg, 0.12mmol) and starting material 1b (25.2mg, 0.1mmol) were added and reacted at 0°C, monitored by TLC until the reaction of starting material 1b was complete. The reaction solution was directly concentrated, and separated and purified by column chromatography to obtain 43.6 mg of product 3b with a yield of 99%.

[0043] White solid, melting point 81-82°C, R f =0.3 (petroleum ether:ethyl acetate=5:1). 1 H NMR (400MHz, Chloroform-d) δ7.68 (s, 1H), 7.49 (d, J = 8.6Hz, 1H), 7.39–7.37 (m, 2H), 7.23 (ddd, J = 20.8, 13.8, 6.4 Hz,8H),6.62(dt,J=7.3,3.6Hz,1H),6.58(d,J=1.5Hz,1H),4.00(s,1H),3.87(s,3H),3.61(s,3H ), 3.07(d, J=13.4Hz, 1H), 2.95(d, J=13.4H...

Embodiment 3

[0046] Preparation of compound 3c

[0047]

[0048] step:

[0049]

[0050] Accurately weigh ligand 3 (21.8 mg, 0.03 mmol) and silver carbonate (4.1 mg, 0.015 mmol) into a 10 mL reaction tube equipped with a stirrer, add 0.5 mL of chloroform and stir at -20°C for 5 minutes. Then isocyanoacetate 2a (22.68mg, 0.12mmol) and starting material 1c (30.1mg, 0.1mmol) were added and reacted at -20°C, monitored by TLC until the reaction of starting material 1c was complete. The reaction solution was directly concentrated, and separated and purified by column chromatography to obtain 44.1 mg of product 3c with a yield of 90%.

[0051] White solid, melting point M.P.73-75℃, R f =0.5 (petroleum ether:ethyl acetate=5:1). 1 H NMR (400MHz, Chloroform-d) δ7.67(s,1H),7.45(d,J=8.2Hz,1H),7.38(s,1H),7.34–7.33(m,2H),7.30–7.28( m,3H),7.24–7.21(m,4H),7.19–7.15(m,2H),3.99(s,1H),3.60(s,3H),3.06(d,J=13.4Hz,1H),2.93 (d,J=13.4Hz,1H); 13 C NMR(101MHz,Chloroform-d)δ195.87,171.94,171.34,159.83,13...

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

A pyrroline derivative with a spirane structure has significant physiological activity in fields such as antibiosis and antiviral actions. The invention relates to an asymmetric synthesis method for apyrroline derivative. According to the asymmetric synthesis method, an ethyl isocyanoacetate compound and an aurone derivative are adopted for a 1,3-dipolar-cycloaddition reaction. Through the reaction, a spirane pyrroline derivative with three continuous chiral centers can be rapidly and efficiently established, and very good atom economy can be achieved. The asymmetric synthesis method is easyin substrate preparation, low in price, in addition, mild in reaction condition and simple in operation, a target compound can be prepared with a high yield and high enantioselectivity without anhydrous anaerobic operation, and the substrate application range is wide.

Description

technical field [0001] The invention belongs to the field of organic synthesis methodology and relates to an asymmetric synthesis method of pyrroline derivatives with a spiro ring structure participated by isocyanides. Background technique [0002] Pyrroline and pyrrolidine skeletons with spiro ring structure are widely found in natural products and biologically active compounds. They have important physiological activities in the fields of antibacterial and antiviral, and are also important intermediates in organic synthesis. Because of their unique In recent years, more and more attention has been paid by synthetic chemists due to their structural characteristics and important biological activities. [0003] In 2012, Wang (Chem.Commun., 2012, 48, 5175-5177) et al. reported that 3-alkenyl-2-indolinone and α-phenyl-substituted isocyanide were catalyzed by cinchona base-derived thiourea. The asymmetric 1,3-dipolar cycloaddition reaction of diethyl acetate, by changing the pr...

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
IPC IPC(8): C07B53/00C07D491/107C07F17/02
CPCC07B53/00C07B2200/07C07D491/107C07F17/02
Inventor 王志鹏向四川邵攀霖贺耘
Owner CHONGQING 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