Preparation method of N-fmoc-D-methionine-O-octanoyl-serine/threonine

The technology of fluorene methoxycarbonyl and fluorene methoxycarbonyl- is applied in the field of preparation of serine/threonine derivatives, which can solve the problems of difficult operation, unenvironmental protection, and difficulty in purification, and achieve the effect of process stability.

Inactive Publication Date: 2019-04-16
GL BIOCHEM SHANGHAI +1
View PDF3 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The purpose of the present invention is to provide a preparation method of N-fluorenylmethoxycarbonyl-O-octanoyl-serine/threonine, which mainly solves the ...

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
  • Preparation method of N-fmoc-D-methionine-O-octanoyl-serine/threonine
  • Preparation method of N-fmoc-D-methionine-O-octanoyl-serine/threonine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0012] Step 1: Dissolve 20g (0.048mol) of N-fluorenylmethoxycarbonyl-L-serine-benzyl ester in 260ml tetrahydrofuran until dissolved. Then add 11.2g (0.0776mol) of n-octanoic acid, cool down to 0 degrees Celsius in an ice-water bath, slowly add 9.78g (0.0776mol) of N,N'-diisopropylcarbodiimide dropwise, and drop N,N'- For diisopropylcarbodiimide, remove the ice-water bath, let it slowly rise to 25 degrees Celsius, and react overnight. The next day, after thin-layer chromatography analysis, the raw material N-fluorenylmethoxycarbonyl-L-serine-benzyl ester had completely reacted and could be processed. Treatment: Suction filter the liquid, slowly evaporate the tetrahydrofuran to dryness at 35 degrees Celsius to obtain an oily substance, dissolve the oily substance with 400ml ethyl acetate, wash the ethyl acetate phase twice with citric acid with a concentration of 5% by mass, After that, it was washed three times with water until pH = 7, washed once with brine, and dried over an...

Embodiment 2

[0015] Step 1: Dissolve 20g (0.048mol) of N-fluorenylmethoxycarbonyl-DL-serine-benzyl ester in 260ml tetrahydrofuran until dissolved. Then add 11.2g (0.0776mol) of n-octanoic acid, 1.2g (0.0098mol) of 1-hydroxybenzotriazole, cool down to 0 degrees Celsius in an ice-water bath, and add 15.8g of N,N'-dicyclohexylcarbodiimide in batches (0.0776mol), after adding N,N'-dicyclohexylcarbodiimide, remove the ice-water bath, let it slowly rise to 25 degrees Celsius, and react overnight. The next day, after thin-layer chromatography analysis, the raw material N-fluorenylmethoxycarbonyl-DL-serine-benzyl ester had completely reacted and could be processed. Treatment: Cool down to 0°C to obtain the liquid, evaporate the tetrahydrofuran to dryness at 35°C to obtain an oily substance, dissolve the oily substance with 400ml of ethyl acetate, wash the ethyl acetate phase twice with 5% citric acid by mass , washed twice with water until pH = 7, washed once with brine, and dried over anhydrous ...

Embodiment 3

[0018] Step 1: Dissolve 20g (0.048mol) of N-fluorenylmethoxycarbonyl-Dserine-benzyl ester in 260ml tetrahydrofuran until dissolved. Add 11.2 g (0.0776 mol) of n-octanoic acid, cool down to 0 degrees Celsius in an ice-water bath, add 14.7 g of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride in batches, and complete the addition 1-Ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, remove the ice-water bath, let it slowly rise to 25 degrees Celsius, and react overnight. The next day, after thin-layer chromatography analysis, the raw material N-fluorenylmethoxycarbonyl-D serine-benzyl ester had completely reacted and could be processed. Treatment: Suction filter the liquid, slowly evaporate the tetrahydrofuran to dryness at 35 degrees Celsius to obtain an oily substance, dissolve the oily substance with 400ml ethyl acetate, wash the ethyl acetate phase twice with citric acid with a concentration of 5% by mass, After that, it was washed three times with water unti...

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

The invention relates to a preparation method of N-fmoc-D-methionine-O-octanoyl-serine/threonine, the preparation method mainly solves the technical problems that a prior synthetic method is difficultto operate, environmental protection cannot be ensured in purification and enlargement production. According to the technical scheme: the preparation method includes the following steps of: using N-fmoc-D-methionine-serine/threonine-benzyl ester as a starting material, carrying out condensation reaction with n-octanoic acid by adding a condensing agent to obtain N- fmoc-D-methionine-O-octanoyl-serine/threonine-benzyl ester, purifying, adding the N- fmoc-D-methionine-O-octanoyl-serine/threonine-benzyl ester in a debenzyl reagent to remove the benzyl through palladium carbon hydrogenation toobtain the N-fmoc-D-methionine-O-octanoyl-serine/threonine. The product has important application in the field of polypeptide medicine.

Description

technical field [0001] The invention relates to a preparation method of a serine / threonine derivative, especially a preparation method of N-fluorenylmethoxycarbonyl-O-octanoyl-serine / threonine. Background technique [0002] In the molecular structure of N-fluorenylmethoxycarbonyl-O-octanoyl-serine / threonine, there is a hydrophobic long carbon chain group - octanoyl, which plays an important role in constructing the spatial structure of active polypeptides. The industrial synthesis method has not been recorded in the literature. Du Xiumin. Preparation of Fmoc Series Protected Amino Acids. "China Excellent Master's Dissertations Full-text Database". 2005, page B014-73. React with N-fluorenylmethoxycarbonyl-serine / threonine (such as Fmoc-Ser-OH) to generate N-fluorenylmethoxycarbonyl-O-octanoyl-serine / threonine (such as Fmoc-Ser(n-Octanoyl )-OH), we tried this reaction, but there were too many miscellaneous points in the latter step, which was difficult to handle, and the octa...

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): C07C269/06C07C271/22
CPCC07C269/06C07C2603/18C07C271/22
Inventor 徐红岩奚文波戴健卢强熙秦丽星周志国
Owner GL BIOCHEM SHANGHAI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap