Optical pure levorotation cephalotaxine and separation purification method

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 ...

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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 pure L-harringtonine (Chinese Journal of Medicinal Chemistry, 1994, 4, 84; J.Org.Chem.1995, 60, 115; Tetrahedron.Asymmetry 1997, 8, 191; J.Am.Chem.Soc.1999, 121, 10246; Chem.Pharm.Bull.1999, 47, 983; J.Org.Chem.2004, 69, 3087; Tetrahedron 2006, 62, 7266; .Chem.Soc.2006,128,10370; J.Org.Chem.2007,72,7352), the synthetic route of these bibliographical reports is tedious, can not be used for large-scale preparation optically pure L-harringtonine; And from three The report on the method of separating and purifying L-harringtonine in the genus Axaphytum is also rare (J.Org.Chem.1963,28,2194; US 3870727; WO 9948894), and these methods need column separation or high performance liquid phase Preparative chromatographic separation can only be achieved with reagents such as chloroform and benzene, and is not suitable for large-scale preparation

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