Total synthesis method of natural product barrenwort glycosides compounds

A technology of icariside and compounds, applied in the field of medicine, can solve the problems of harsh reaction conditions, low reaction yield, insufficient research, etc., and achieve the effect of increased yield, high yield, and easy availability of raw materials

Inactive Publication Date: 2010-10-06
李毅林
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0027] Therefore, the current research on the glycosylation reaction of flavonoids is not sufficient, especially the research on the glycosylation method of prenyl flavones similar to the structure of dehydroicariin is basically blank
[0028] In summary, although there have been reports on total synthesis methods of other prenyl flavonoids with similar structures, these synthesis methods or reaction yields are low, or raw materials are not easy to obtain, and the reaction conditions are harsh, so they are not suitable for industrialization. production, and so far there has been no report of applying these methods to the synthesis of icariin
Simultaneously, the method for further applying existing methods to synthesize icariin from aglycon has not been reported yet.

Method used

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  • Total synthesis method of natural product barrenwort glycosides compounds
  • Total synthesis method of natural product barrenwort glycosides compounds
  • Total synthesis method of natural product barrenwort glycosides compounds

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Embodiment 1

[0075] The following examples are used to illustrate the present invention, but not to limit the scope of the present invention. Example 1 Synthesis of compound A: dehydrated icariin (anhydroicartin), R 1 =H, R 2 =H

[0076] 1) Synthesis of chloromethyl anisole ii: Mix benzyl alcohol (108g, 1.0mol) with paraformaldehyde (30g, 1.0mol as HCHO), keep the mixture at 0℃ in an ice bath, and quickly pass in hydrochloric acid gas and Keep at 0°C and stir vigorously for 4 hours. After stopping stirring and raising to room temperature, the mixture was separated into layers, the upper organic phase was separated, 500ml petroleum ether was added, dried over anhydrous magnesium sulfate for 1 hour and filtered out, a small amount of anhydrous calcium chloride was added and concentrated to obtain an oily substance. Under reduced pressure distillation, 106 g of colorless liquid compound ii (70-72° C., 3 mmHg) was obtained, with a yield of 68%.

[0077] 2) Synthesis of cyanomethyl anisole iii: Ad...

Embodiment 2

[0089] Example 2 Synthesis of Compound B: Icariside I (Icariside I), R 1 =H, R 2 =Glc

[0090] Synthesis of anhydroicariin-7-O-β-tetraacetyl-D-glucopyranoside xiii: Compound A anhydroicariin (1g, 2.7mmol) was added to dry pyridine (20ml), stirred to dissolve Then, add silver nitrate (0.9g, 5.4mmol) and powdered 4A molecular sieve (2.0g). After stirring for 1 hour in the dark at room temperature, add α-bromotetraacetyl-D-glucopyranose (1.22g, 2.9 After stirring at room temperature and dark for 48 hours, the reaction solution was diluted with 100ml chloroform, filtered through Celite to remove silver salt and molecular sieve, and the filtrate was washed with 100ml 1mol / L hydrochloric acid and 100ml saturated sodium chloride aqueous solution in turn, anhydrous After drying, filtering and concentrating over magnesium sulfate, the residue was purified by silica gel column chromatography (gradient elution, eluent ratio: acetone: petroleum ether = 2:8-4:6) to obtain 1.06 g of yellow sol...

Embodiment 3

[0093] Example 3 Synthesis of Compound C: Icariside II (Icariside II), R 1 = Rham, R 2 =H

[0094] Synthesis of 7-O-tert-butyldimethylsilyl dehydrated icariin xiv: compound dehydrated icariin A (1g, 2.7mmol) and diisopropylethylamine (1.1ml, 6.0mmol) at room temperature Dissolve it in 15ml of dichloromethane, keep stirring at 0℃ in an ice bath, and add tert-butyldimethylchlorosilane (450mg, 3.0mmol) in 5ml of dichloromethane dropwise. After the addition is complete Remove the ice bath, warm to room temperature, stir for 4 hours, add 50ml 0.5mol / L hydrochloric acid, separate the dichloromethane phase, and then extract the aqueous phase with 3×20ml dichloromethane, combine the organic phases, and use saturated sodium chloride solution After washing, drying over anhydrous magnesium sulfate, filtering and concentration, purification by silica gel column chromatography (gradient elution, eluent ratio: acetone: petroleum ether = 5:95-10:90) to obtain 1.01g yellow solid compound xiv, t...

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Abstract

The invention provides a total synthesis method for preparing the icariin compound with a structural formular as (I); R<1> symbolizes H or Rham and R<2> symbolizes H or Glc. By adopting the Claisen rearrangement reaction triggered by the microwave, the method leads the isopenteny in with positioning on the flavone ring with high selectivity so as to enhance the overall yield and lead to the easily obtained raw materials and higher yield of the icariin compound. The invention is suitable for industrialized production and solves the problem that the compound can be only prepared through extraction and separation in the Chinese herbal medicine extractum with extremely low efficiency.

Description

Technical field [0001] The invention relates to a method for preparing a natural product icariin (icariin in English) compound through total synthesis, and belongs to the technical field of medicine. Background technique [0002] Icariin is a flavonoid glycoside compound in the epimedium genus of the Berberis family. Epimedium as a tonic Chinese medicine was first published in the "Shen Nong's Materia Medica" for more than 2,000 years. It is one of the most widely used and longest Chinese medicines in China. There are five kinds of epimedium in the "Pharmacopeia of the People's Republic of China". Genus of plants. Traditional medicine believes that Epimedium has the effects of nourishing kidney yang, strengthening muscles and bones, and dispelling rheumatism. It can be used to treat hypertension, coronary heart disease, osteoporosis, menopausal syndrome, impotence, hemiplegia, and numbness of the limbs. As one of its main effective ingredients, icariin has attracted the attenti...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H17/07C07D311/30
Inventor 李毅林朱轶才张洁崔丽妍
Owner 李毅林
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