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

Synthetic method of cis-fused ring β-lactam compound

A technology of lactam compound and synthesis method, applied in the field of synthesis of β-lactam compound, capable of solving problems such as stereo and enantioselectivity

Inactive Publication Date: 2016-04-13
KUNMING INST OF BOTANY - CHINESE ACAD OF SCI
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The third route, as shown in Scheme 3, uses the intramolecular Staudinger reaction as the key step (Muller, et al., WO2009037229A1, 2009), but requires the use of chiral prosthetic groups, and there are problems with stereo and enantioselectivity

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
  • Synthetic method of cis-fused ring β-lactam compound
  • Synthetic method of cis-fused ring β-lactam compound
  • Synthetic method of cis-fused ring β-lactam compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] (1) Preparation of Compound 1 (1):

[0059]

[0060] The operation is as follows: at room temperature, NaOH (0.8g, 20mmol) was added to 50ml of aqueous solution, and after cooling to room temperature, L-proline (1.15g, 10mmol) was added to the above solution. Then a solution of CbzCl (2.05g, 12mmol) in 50ml THF was slowly added dropwise. The reaction was maintained for 4 hours. The reaction solution was acidified with HCl (2M) aqueous solution to Ph=3, extracted three times with ethyl acetate (3x100ml), the organic layer was washed with saturated brine (50ml), dried over anhydrous sodium sulfate, and spin-dried. with CHCl 3 : MeOH=20:1 was passed through the column to obtain 2.36g of compound 1, and the yield was 95%. 1 HNMR (400MHz, CDCl 3 )δ11.2(s,1H),7.48–7.36(m,5H),5.12(s,2H),4.25-4.10(m,1H),3.40-3.31(m,2H),2.01-1.62(m, 4H); 13 CNMR (100MHz, CDCl 3 ) δ 175.9, 154.3, 136.1, 127.6, 129.0, 127.1, 65.8, 50.1, 28.5, 24.4.

[0061] (2) Preparation of Compound 2...

Embodiment 2

[0074] (6) Preparation of Compound 17 (17):

[0075]

[0076] The operation is as follows: at room temperature, NaOH (0.8g, 20mmol) was added to 50ml of aqueous solution, and after cooling to room temperature, L-octahydroindole-2-carboxylic acid (1.69g, 10mmol) was added to the above solution. Then a solution of CbzCl (2.05g, 12mmol) in 50ml THF was slowly added dropwise. The reaction was maintained for 4 hours. After acidifying with HCl (2M) aqueous solution to Ph=3, it was extracted three times with ethyl acetate (3x100ml), and the organic layer was washed with saturated brine (50ml), dried over anhydrous sodium sulfate, and spin-dried. with CHCl 3 : MeOH=20:1 column to obtain 2.09g compound 1, yield 69%. Spectral data are consistent with literature reports (Eur.J.Org.Chem.2008,934–940).

[0077] (7) Preparation of Compound 18 (18):

[0078]

[0079] The operation was as follows: 5-methoxy-8-aminoquinoline (1.74g, 10mmol), 17 (3.64g, 12mmol), EDCI (2.88g, 15mmol),...

Embodiment 3

[0090] (11) Preparation of Compound 6 (6):

[0091]

[0092] The operation is as follows: Put DMF·SO 3 (1.43g, 9.35mmol) was added to a solution of 5 (1.8g85mmol) in DMF (20ml), and the temperature was kept at 5°C for 3h. Spin off part of the solvent, add 10ml of water, stir overnight, and then recrystallize to obtain 0.94g of compound 6, with a yield of 57%. Spectral data are consistent with literature reports (J.Med.Chem.1998,41,3961-3971).

[0093] (12) Preparation of Compound 7d (7d):

[0094]

[0095] The operation is as follows: mix 6 (192mg, 1mmol), NaHCO 3 (168mg, 2mmol), 18 (255.2mg, 1mmol) was added to MeCN:H 2 React in a solvent of O (5:2) for 24 hours, add HCl (2M) to acidify to Ph=2 after rotary steaming the above solution, and use CH 2 Cl 2 (3x50ml) was extracted 3 times, the organic layer was washed with saturated brine (50ml), dried over anhydrous sodium sulfate, and spin-dried. with CHCl 3 :MeOH=10:1 column to obtain 273mg of compound 7d, yield 8...

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 synthetic method for a class of cis-fused ring β-lactam compounds shown in formula (I), using substituted or unsubstituted pyrrole-2-carboxylic acid, or substituted or unsubstituted pyridine-2-carboxylic acid, or substituted or Unsubstituted indole-2-carboxylic acid as the starting material, using Pd(II) as the catalyst, AgOAc or Ag2CO3 as the oxidant, activating the sp3C-H bond at the β position of the amide substrate 2 (such as Scheme4) by palladium catalysis , while intramolecular C-N bond formation occurs, and the successful construction of a cis-fused ring β-lactam skeleton is a key step. The raw material of the present invention is simple and easy to obtain, low in price, simple in experimental operation, short in route, high in yield, high in atom economy, less in waste, good in environment, wide in scope of substrate application, good in universality and high in energy efficiency Optically active β-lactam compounds with chiral retention can be obtained.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and in particular relates to a synthesis method of a kind of cis-fused ring β-lactam compound represented by formula (I). Background technique [0002] Carbapenem antibiotics (such as imipenem) are a very important class of drugs used to treat bacterial infections and have been used clinically for more than 20 years. However, in recent years, some Pseudomonas strains have developed resistance to carbapenems by losing porins or expressing β-lactamases. These β-lactamases inactivate carbapenems by hydrolysis. According to the structure, hundreds of known β-lactamases can be divided into four types A-D. Type A β-lactamases are the main cause of penicillin resistance. Carbapenem resistance caused by Pseudomonas strains is mainly produced by C-type β-lactamases such as AmpC. After years of research, scientists have discovered that some β-lactamase inhibitors have a good inhibitory effect on the e...

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): C07D487/04C07D471/04
CPCC07D471/04C07D487/04
Inventor 吴滨孙文武
Owner KUNMING INST OF BOTANY - CHINESE ACAD OF SCI