Optical pure levorotation cephalotaxine and separation purification method

A technology of L-harringtonine and harringtonine, which is applied in the field of separation and purification of optically pure L-harringtonine, and can solve problems such as lengthy synthesis lines

Inactive Publication Date: 2009-07-29
NANKAI UNIV
View PDF4 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Optically active harringtonine is the key to the semi-synthetic anti-leukaemic drug harringtonine (harringtonine, homoharringtonine, deoxyharringtonine and isoharringtonine and their analogs) Precursor compounds (The Alkaloids: Chemical and Biological Perspectives 1987, 5, 639; The Alkaloids, 1998, 51, 199; Journal of Lanzhou University (Natural Science Edition), 1974, 1, 148; Chinese Science (Eng.), 1979, 22, 1333; J.Org.Chem., 1978, 43, 4762; Science Bulletin, 1975, 20, 437; Acta Pharmaceutica Sinica, 1980, 15, 46; Science Bulletin, 1980, 25, 576; Tetrahedron Lett.1982, 23 , 3431; Science Bulletin, 1982, 27, 1048; Acta Pharmaceutica Sinica 1982, 17, 866; Acta Pharmacina Sinica 1992, 47, 1087; J.Org.Chem.1979, 44, 63; Tetrahedron Lett.1999, 40, 2931; CN1300289A , 1999), there are few reports on the chemical synthesis of optically p

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
  • Optical pure levorotation cephalotaxine and separation purification method
  • Optical pure levorotation cephalotaxine and separation purification method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Example 1 Extraction and purification of L-harringtonine from the total alkaloid extract of harringtonine

[0019] Get 48.4 grams of extract (prepared by the method of document J.Org.Chem.1963,28,2194, solid content 57%, containing alkaloids such as harringtonine, harringtonine and homoharringtonine), Add 300mL of water and 150mL of dichloromethane, stir, add 38mL of 2M hydrochloric acid solution dropwise, adjust the water phase to pH = 3, separate the layers, then extract the water layer with dichloromethane for 1-2 times, combine the organic phases, and recover the organic phase , to obtain trace amounts of non-alkali organic compounds and pigments.

[0020] While stirring the aqueous layer, add 42 mL of 2M aqueous sodium hydroxide solution to adjust the pH to 13, add 150 mL of diethyl ether, and stir overnight at room temperature. Add 50mL of 2M hydrochloric acid solution dropwise under stirring, adjust the water phase to pH=3, separate the liquid, then extract the ...

Embodiment 2

[0024] Example 2 Separation and purification of L-harringtonine from the residual extract after extracting harringtonine

[0025] Get 100 grams of residual extract after extracting harringtonine (solid content is about 43%, mainly harringtonine, content about 80%, excluding solvent content in the extract; document: Phytochemistry, 1972, 11, 1467) Put it into a beaker, add 500 mL of distilled water and 250 mL of dichloromethane, stir, add dropwise 70 mL of 2 M hydrochloric acid solution, adjust the water phase to pH=3, separate the layers, and then extract the water layer 1-2 with dichloromethane The second time, the organic phase is combined, and the organic phase is recovered to obtain a trace amount of non-alkali organic matter and pigment.

[0026] Add 200 mL of diethyl ether to the water layer, adjust the pH of the water phase to 13 with 75 mL of 2M sodium hydroxide solution, and stir overnight at room temperature. Add 82 mL of 2M hydrochloric acid solution dropwise under...

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
Melting pointaaaaaaaaaa
Login to view more

Abstract

The invention relates to a separation and purification method of optically pure levorotatory cephalotaxine. The levorotatory optically pure cephalotaxine is colorless transparent acicular crystal, the optical purity is larger than 99 percent, the specific rotatory power [alpha]D is equal to -194 degrees[c 1.02, CHCl3, 20 DEG C], and the melting point is 143-144 DEG C. Cephalotaxus fortunei biological total alkali extract extracted from cephalotaxus plants or residual extract after cephalotaxus ester base is extracted from the cephalotaxus plants is used as raw material, mixed solvent of water and dichloromethane is used for dissolving the raw material, and the dichloromethane is firstly used for the extraction under acid condition; separated water phases are successively extracted by ether under alkali condition and methylene dichloride under acid condition; the water phases are extracted by the ether under the alkali condition, ether phases are condensed and crystallized to obtain the target product. The method has the advantages of simple operation, safety, reliability, high efficiency, high yield and low cost and can easily realize the scale preparation of the optically pure levorotatory cephalotaxine.

Description

technical field [0001] The invention relates to the separation of harringtonine, in particular to a separation and purification method for optically pure L-harringtonine. Background technique [0002] Cephalotaxine (Cephalotaxine) widely exists in the roots, stems, leaves, stems and fruits of Cephalotaxus, accounting for 40%-80% of the total biological alkaloids contained in Cephalotaxus ("Three Jianshan Biology", Hu Yuxi, Science Press, 1999, pp106). Optically active harringtonine is the key to the semi-synthetic anti-leukaemic drug harringtonine (harringtonine, homoharringtonine, deoxyharringtonine and isoharringtonine and their analogs) Precursor compounds (The Alkaloids: Chemical and Biological Perspectives 1987, 5, 639; The Alkaloids, 1998, 51, 199; Journal of Lanzhou University (Natural Science Edition), 1974, 1, 148; Chinese Science (Eng.), 1979, 22, 1333; J.Org.Chem., 1978, 43, 4762; Science Bulletin, 1975, 20, 437; Acta Pharmaceutica Sinica, 1980, 15, 46; Science ...

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): C07D491/153A61K36/13A61P35/02
Inventor 李卫东陈莉
Owner NANKAI UNIV
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