Optical active compound of anti-infective prulifloxacin and preparation method thereof

A compound and star optical technology, which is applied in the field of antibacterial agents of thiazetidine quinoline carboxylic acids to achieve the effect of enhanced antibacterial effect and low toxicity

Active Publication Date: 2010-07-07
HAINAN HUALON PHARM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There is a carbon atom chiral center (1-C) in the structural formula of prulifloxacin, b

Method used

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  • Optical active compound of anti-infective prulifloxacin and preparation method thereof
  • Optical active compound of anti-infective prulifloxacin and preparation method thereof
  • Optical active compound of anti-infective prulifloxacin and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Preparation of (S)-(-)-Ulifloxacin

[0039] Dissolve 105 g of racemic Ulifloxacin in 1500 mL of dimethyl sulfoxide, add dropwise a solution of 27 g of D-tartaric acid in 405 mL of dimethyl sulfoxide with stirring, stir at room temperature for 20 hours, and precipitate and filter. The solid was dried under vacuum to obtain 86 grams. This solid was recrystallized in dimethyl sulfoxide to obtain 37 grams of levofloxacin-D-tartrate. After elemental analysis, C49.08%, H5.06%, N9. 50%, S7.44% (Molecular composition: C 16 H 16 FN 3 O 3 S·1 / 2C 4 H 6 O 6 ·H 2 O, calculated value C48.86%, H4.78, N9.50%, S7.25%); add this salt to water to form a suspension, adjust the pH to 7-8 with 2% NaOH aqueous solution while stirring, and filter the precipitate After drying, 24.5 g of (S)-Ulifloxacin was obtained, its chemical name: (S)-(-)-6-fluoro-1-methyl-4-oxo-(1-piperazinyl)-1H, 4H -[1,3]thiazetidine[3,2-a]quinoline-3-carboxylic acid

[0040] Specific rotation (c=0.5, 0.1mol / L me...

Embodiment 2

[0041] Example 2 Preparation of (R)-(+)-Ulifloxacin

[0042] Dissolve 105 g of racemic Ulifloxacin in 1500 mL of DMSO, add 27 g of L-tartaric acid in 405 mL of dimethyl sulfoxide solution dropwise with stirring, turbidity and precipitation appear, stir at room temperature for 20 hours, and filter to obtain The solid was dried under vacuum to obtain 82 grams. The solid was recrystallized and purified in dimethyl sulfoxide to obtain 34 grams of dextro-Ulifloxacin-L-tartrate. The salt was added to the water to form a suspension and used under stirring. Adjust the pH to 7-8 with 2% NaOH aqueous solution, filter and dry to obtain 22 grams of (R)-Ulifloxacin, its chemical name: (R)-(+)-6-fluoro-1-methyl-4-oxy -(1-piperazinyl)-1H,4H-[1,3]thiazetidine[3,2-a]quinoline-3-carboxylic acid

[0043] Specific rotation (c=0.5, 0.1mol / L methanesulfonic acid), optical purity e.e. 96%.

Embodiment 3

[0044] Example 3 Preparation of S-(-)-Prulifloxacin

[0045] Take 3.49g (0.01mol) of S-(-)-Ulifloxacin prepared in Example 1, 2.02g (0.02mol) of triethylamine and 20ml of N,N-dimethylformamide (abbreviated as DMF, the same below) and mix Stir, drop the temperature to -5~5℃ and add 4-bromomethyl-5-methyl-1,3-dioxol-2-one (abbreviated as DMDO-Br, the same below) 0.012mol of DMF( 5ml) solution, continue to stir at -5~5°C for 3 hours, pour the reaction solution into 100ml ice water, stir for 30 minutes, filter, wash with water, collect the solid and vacuum dry. It was recrystallized from acetonitrile to obtain 2.9 g of S-(-)-Prulifloxacin, chemical name: S-(-)-6-fluoro-1-methyl-7-[4-(5-methyl-2- Oxo-1,3-dioxol-4-yl)methyl-1-piperazinyl]-4-oxo-4H-[1,3]thiazetidine[3, 2-α]quinoline-3-carboxylic acid, 98% purity. The yield was 63%. Specific rotation (c=0.5, 0.1mol / L methanesulfonic acid)

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Abstract

An optical active compound of anti-infective prulifloxacin and a preparation method thereof relate to an antimicrobial agent of optical active sulfur-nitrogen oxetane and quinoline carboxylic acid, and a preparation method. The compound of the invention takes the following formula 1 to show the compound and salt thereof, the stereo configuration is in S configuration, and the compound has the optical activity of levorotary deviated light; the compound and the salt for medical purpose can be added with pharmaceutical adjuvant to make into preparations for oral use; the method comprises: taking levorotary ulifloxacin as raw material, putting into an organic solvent, and reacting under the condition of the existence of alkali substance, with the reaction temperature of 20 DEG C below zero to 60 DEG C, and the reaction time of 15min to 24h. The levorotary prulifloxacin and physically allowed salt thereof can substitute for the existing antibacterial prulifloxacin and physically allowed salt thereof, not only antibacterial action is obviously improved, but also the toxicity is little.

Description

Technical field [0001] The invention relates to an optically active antibacterial agent of thiazetidine quinoline carboxylic acid and a preparation method. Specifically, it relates to an optically active compound of prulifloxacin, its oral preparation and a preparation method thereof. Background technique [0002] Quinolones are a class of anti-infectives synthesized in recent years. They are widely used clinically in the treatment of respiratory system, gastrointestinal tract, urinary system, dermatology, gynecology, surgery and other fields, with good results. Prulifloxacin, chemical name (±)6-fluoro-1-methyl-7-[4-(5-methyl-2-oxo-1,3-dioxol-4-yl) )Methyl-1-piperazinyl]-4-oxo-4H-[1,3]thiazetidine[3,2-α]quinoline-3-carboxylic acid, a joint venture with Japan New Drug A quinolone drug jointly developed by Meiji Confectionery. Pralifloxacin is a third-generation fluoroquinolone broad-spectrum antibacterial drug, which has a broad-spectrum antibacterial effect on gram-positive an...

Claims

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Application Information

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IPC IPC(8): C07D513/04A61K31/496A61P31/00A61P31/04
CPCC07D513/04A61K31/496A61P31/00A61P31/04
Inventor 应军彭锋王玉平安穗伟梁金强梁北梅倪庆纯罗成
Owner HAINAN HUALON PHARM
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