Unlock instant, AI-driven research and patent intelligence for your innovation.

A preparation method of optically active adjacent double-spiro epoxy indole compounds

A technology of oxindole and optical activity, applied in organic chemistry methods, organic chemistry, etc., can solve the problems of limited, difficult structural units, lack of technical design, etc., and achieve the effects of high optical purity, convenient operation, and simple equipment

Active Publication Date: 2019-12-03
ZUNYI MEDICAL UNIVERSITY
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the prior art mainly focuses on the synthesis of racemates of such compounds, and there are very limited reports on the asymmetric synthesis of chiral double-spiro ring oxindole compounds containing adjacent spirocyclic quaternary carbon centers, mainly because the construction of at least Containing two adjacent chiral centers and a very crowded double-spiro epoxy indole building block is very difficult
In addition, the existing techniques for the asymmetric synthesis of such compounds mainly focus on the organocatalytic [3+2] cyclization cascade reaction, and the synthesized molecules are mainly 3,3'-tetrahydropyrrole / dihydrofuran- Bispiroepoxindole, the asymmetric synthesis of chiral 3,3'-cyclopentene-bispiroepoxindole is still a challenging problem due to the lack of effective technical design Work

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
  • A preparation method of optically active adjacent double-spiro epoxy indole compounds
  • A preparation method of optically active adjacent double-spiro epoxy indole compounds
  • A preparation method of optically active adjacent double-spiro epoxy indole compounds

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0032] The invention provides a method for preparing optically active adjacent double-spiro epoxy indole compounds, comprising:

[0033] Step 1, adding isatin-derived MBH-carbonate, 3-carbonyl benzoheterocyclic compound and chiral Lewis base into an organic solvent, stirring at a reaction temperature of 0°C to 50°C;

[0034] Step 2: Separating and obtaining optically active adjacent double-spiro epoxy indole compounds.

[0035] For example: Dissolve 0.2mmol 3-carbonyl benzoheterocyclic compound, 0.3mmol isatin-derived MBH-carbonate and 0.04mmol (12.4mg) β-6'-hydroxyisocinchonine in 2mL dichloromethane, Stir for 5 hours at a reaction temperature of 25°C; then, the reaction solution is directly separated by column chromatography to obtain the corresponding optically active adjacent double-spiro epoxy indole compounds.

[0036] The present invention is by dissolving β-6'-hydroxyisocinchonine, isatin derived MBH-carbonate and 3-oxoalkenyl oxide indole (or 3-oxoalkenyl benzofuran-...

Embodiment 1

[0039] Add 0.3mmol (104.1mg) of 2-(1-methyl-3-tert-butoxycarbonyloxy-2-oxindoline-3-yl) methyl acrylate to 2mL of dichloromethane, 0.2mmol (52.7 mg) of 1-methyl-3-(2-oxo-2-phenylethylidene)indoline-2-one and 12.4mg of β-6'-hydroxyisocinchonine, the mixture was at a reaction temperature of 25°C Stir for 5 hours and monitor the progress of the reaction by thin layer chromatography. After the reaction was completed, the mixture was separated and purified by column chromatography to obtain (C1R, C4R, C5S)-3,3'-(1-benzoyl)cyclopentenyl adjacent double spiroepoxindole (yield 89 %, dr value 97:3, ee value>99%).

[0040]

[0041] Characterization data of (C1R,C4R,C5S)-3,3'-(1-benzoyl)cyclopentenyl-adjacent double-spiro epoxy indole: [α] D 25 =-101.0 (c 1.00, CHCl 3 ); mp 230.1-231.2℃. The ee was determined by HPLC (Chiralpak AD-H, i-PrOH / hexane=30 / 70, flow rate 1.0mL / min, λ=254nm, majordiastereomer:t major =10.5min). 1 H NMR (400MHz, CDCl 3 ):δ2.98(3H,s),3.05-3.06(3H,m),3.62-3...

Embodiment 2

[0043] Add 0.3 mmol (108.4 mg) of 2-(1,5-dimethyl-3-tert-butoxycarbonyloxy-2-oxindoline-3-yl) methyl acrylate to 2 mL of dichloromethane, 0.2 mmol (52.7 mg) of 1-methyl-3-(2-oxo-2-phenylethylidene) indoline-2-one and 12.4 mg of β-6'-hydroxyisocinchonine, the mixture was heated at 25°C Stirring was carried out at the reaction temperature for 5 hours, and the progress of the reaction was monitored by thin-layer chromatography. After the reaction is complete, the mixture is separated and purified by column chromatography to obtain (C1R, C4R, C5S)-3,3'-(1-benzoyl)cyclopentenyl-5-methyl-adjacent double spiroepoxide Indole (yield 70%, dr value >99:1, ee value 99%).

[0044]

[0045] Characterization data for (C1R,C4R,C5S)-3,3'-(1-benzoyl)cyclopentenyl-5-methyl-adjacent double-spiro epoxy indole: [α] D 25 =-40.7 (c 0.50, CHCl 3 ); mp 218.7-220.3℃. The ee was determined by HPLC (Chiralpak AD-H, i-PrOH / hexane=30 / 70, flow rate 1.0mL / min, λ=254nm, majordiastereomer:t major =7.8mi...

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

PropertyMeasurementUnit
optical purityaaaaaaaaaa
Login to View More

Abstract

The invention discloses a preparation method of an adjacent double-spiro oxoindole compound with optical activity in the field of organic synthesis. Chiral lewis base, isatin derived MBH-carbonic ester and 3-carbonyl alkenyl benzoheterocycle compounds are dissolved in organic solvents, the isatin derived MBH-carbonic ester and the 3-carbonyl alkenyl benzoheterocycle compounds are subjected to asymmetric [3+2] cycloaddition reaction under catalysis of the chiral lewis base to generate the adjacent double-spiro oxoindole compound with high optical purity (high dr and ee), a product can be separated by a simple column chromatography or chromatography to obtain the adjacent double-spiro oxoindole compound with the optical activity, the method is mild in reaction condition, proper in temperature and convenient to operate, equipment is simple, and the prepared chiral compound is high in optical purity.

Description

technical field [0001] The invention relates to the field of organic synthesis, more specifically, the invention relates to a preparation method of optically active adjacent double-spiro ring oxixindole compounds. Background technique [0002] As a particularly important class of heterocyclic structural units, spirooxindole is the core skeleton of many active pharmaceutical molecules and natural products, and has attracted special attention from synthetic chemists. Among them, spirocyclic oxindole compounds containing adjacent spirocyclic quaternary carbon centers have been found to have a wide range of pharmaceutical activities, such as antitumor activity and antibacterial activity. In particular, the double-spiro epoxy indole molecules with adjacent spiro quaternary carbon centers often show special physiological activities due to their unique three-dimensional spatial structure. [0003] In view of the good biological activity of the double-spiro epoxy indole molecules w...

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): C07D487/10
CPCC07B2200/07C07D487/10
Inventor 崔宝东陈羽陈永正韩文勇
Owner ZUNYI MEDICAL UNIVERSITY