Preparation method of actinonin

A technology of actinamide and amide condensation, applied in the field of actinamide preparation, can solve problems such as inconvenient operation, compound chiral center racemization, difficult to remove by-products, etc.

Inactive Publication Date: 2017-08-11
EAST CHINA NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But this method needs to use condensing agent such as DCC, the by-product that generates is difficult to remove, and product is difficult to purify, also easily causes the chiral center racemization of compound etc. simultaneously; Need to remove water and the reaction requires ultra-low temperature, the reaction is inconvenient to operate

Method used

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  • Preparation method of actinonin
  • Preparation method of actinonin
  • Preparation method of actinonin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0081] Synthesis of Compound 3

[0082]

[0083] N-Boc-L-prolinol (6.03g, 30mmol) was weighed and dissolved in dry DMF (60mL), under nitrogen protection, and cooled in an ice-water bath. NaH (1.5 g, 37.5 mmol) was added in one portion and stirred for 30 min. Then, BnBr (5.36g, 31.5mmol) was weighed and dissolved in dry DMF (17.5mL), and added dropwise to the above reaction solution within 15min at 0°C. After the addition, the system was naturally raised to room temperature and stirred overnight. Add water to quench the reaction, extract with ethyl acetate (2×100mL), wash the organic phase with water (80mL) and saturated brine (60mL) respectively, dry over anhydrous sodium sulfate, filter, and concentrate the filtrate under reduced pressure to obtain a light yellow oily crude product , the crude product was separated and purified by column chromatography to obtain compound 3 (7.94 g, 91%) as a colorless oil. 1 H NMR (400MHz, CDCl 3 )δ7.39–7.17(m,5H),4.52(s,2H),3.96(d,J=47.6...

Embodiment 2

[0097] Synthesis of Compound 3

[0098]

[0099] N-Boc-L-prolinol (3.02g, 15mmol) was weighed and dissolved in dry DMF (30mL), under nitrogen protection, and cooled in an ice-water bath. NaH (0.9 g, 22.5 mmol) was added in one portion and stirred for 30 min. Then, BnBr (2.81g, 16.5mmol) was weighed and dissolved in dry DMF (7.5mL), and added dropwise to the above reaction solution at 0°C within 15min. After the addition, the system was naturally raised to room temperature and stirred overnight. Add water to quench the reaction, extract with ethyl acetate (2×50mL), wash the organic phase with water (30mL) and saturated brine (30mL) respectively, dry over anhydrous sodium sulfate, filter, and concentrate the filtrate under reduced pressure to obtain a light yellow oily crude product , the crude product was separated and purified by column chromatography to obtain compound 3 (3.80 g, 87%) as a colorless oil. 1 H NMR (400MHz, CDCl 3 )δ7.39–7.17(m,5H),4.52(s,2H),3.96(d,J=47.6...

Embodiment 3

[0113] Synthesis of Compound 3

[0114]

[0115] N-Boc-L-prolinol (4.03g, 20mmol) was weighed and dissolved in dry DMF (40mL), under nitrogen protection, and cooled in an ice-water bath. NaH (1.08 g, 27 mmol) was added in one portion and stirred for 30 min. Then, BnBr (3.64g, 21.4mmol) was weighed and dissolved in dry DMF (7.5mL), and added dropwise to the above reaction solution within 15min at 0°C. After the addition, the system was naturally raised to room temperature and stirred overnight. Add water to quench the reaction, extract with ethyl acetate (2×50mL), wash the organic phase with water (30mL) and saturated brine (30mL) respectively, dry over anhydrous sodium sulfate, filter, and concentrate the filtrate under reduced pressure to obtain a light yellow oily crude product , the crude product was separated and purified by column chromatography to obtain compound 3 (4.54 g, 78%) as a colorless oil. 1 H NMR (400MHz, CDCl 3 )δ7.39–7.17(m,5H),4.52(s,2H),3.96(d,J=47.6H...

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PUM

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Abstract

The invention discloses a preparation method of actinonin. The preparation method includes: taking N-Boc-L prolinol as a raw material; firstly, protecting hydroxyl, and then removing Boc protection base of amino; condensing with N-Boc-L-valine to obtain dipeptide; then removing the amino protection base of the dipeptide, and condensing with acid to obtain tripeptide; hydrolyzing tert-butyl ester of the tripeptide, and condensing with benzohydroxylamine hydrochloride to obtain tetrapeptide; finally, isolating from benzyl protection under the condition of catalytic hydrogenation to obtain the actinonin. The preparation method is low in cost, simple in operation, and able to efficiently prepare the actinonin in a stereoselective manner.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, and in particular relates to a preparation method of actinamide. Background technique [0002] Actinonin is the first reported natural product with peptide deformylase inhibitory activity. In 1962, Gordon et al. in England reported the discovery process of actinamide for the first time in Nature, 1962, pages 701-702. They isolated from actinomycetes the active substance of inhibiting mycobacteria and staphylococcus - actinomycetin. Actinamide has a certain weak acidity, and its molecular formula is C 19 h 35 o 5 N 8 , It can exist stably under alkaline conditions at low temperature and is soluble in water, alcohol and pyridine. In vitro experiments have inhibitory activity on most Gram-positive bacteria and Gram-negative bacteria such as Staphylococcus aureus and Faecalibacterium. The antibacterial mechanism of actinamide was first reported by Chen et al. in Biochemistry, 2000...

Claims

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Application Information

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IPC IPC(8): C07D207/09
CPCY02P20/55C07D207/09
Inventor 胡文浩蔡星汤洋
Owner EAST CHINA NORMAL UNIVERSITY
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