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Total synthesis method of natural product barrenwort glycosides compounds

A technology of icariin and compound, applied in the field of medicine, can solve the problems of harsh reaction conditions, low reaction yield, insufficient research and the like, and achieves the effects of easy availability of raw materials, high yield and improved yield

Inactive Publication Date: 2008-06-25
李毅林
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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

Examples

Experimental program
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Effect test

Embodiment 1

[0077] Example 1 synthetic compound A: dehydrated icariin (icariin, anhydroicartin), R 1 = H, R 2 =H

[0078] 1) Synthesis of chloromethyl anisole ii: mix benzyl alcohol (108g, 1.0mol) with paraformaldehyde (30g, 1.0mol by HCHO), keep the mixture at 0°C in an ice bath, quickly feed hydrochloric acid gas and Keep at 0°C with vigorous stirring for 4 hours. After stopping the stirring and warming to room temperature, the mixture was separated into layers, the upper organic phase was separated, 500ml of petroleum ether was added, dried over anhydrous magnesium sulfate for 1 hour and filtered off, a small amount of anhydrous calcium chloride was added and concentrated to obtain an oily substance. Distillation under reduced pressure gave 106 g of compound ii as a colorless liquid (70-72° C., 3 mmHg), with a yield of 68%.

[0079] 2) Synthesis of cyanomethyl anisole iii: Add cuprous cyanide (66 g, 0.74 mol) to the solution obtained by dissolving compound ii (106 g, 0.68 mol) in 12...

Embodiment 2

[0091] Example 2 Synthesis of Compound B: Icariside I (Icariside I), R 1 = H, R 2 =Glc

[0092] Synthesis of dehydroicariin-7-O-β-tetraacetyl-D-glucopyranoside xiii: Compound A dehydroicariin (1 g, 2.7 mmol) was added to dry pyridine (20 ml), stirred and dissolved Afterwards, silver nitrate (0.9g, 5.4mmol) and powdered 4A molecular sieves (2.0g) were added, and after stirring at room temperature in the dark for 1 hour, α-bromotetraacetyl-D-glucopyranose (1.22g, 2.9 mmol), after continuing to stir at room temperature in the dark for 48 hours, the reaction solution was diluted with 100ml chloroform, filtered through diatomaceous earth to remove silver salts and molecular sieves, and the filtrate was washed successively with 100ml1 mol / liter hydrochloric acid and 100ml saturated aqueous sodium chloride solution, anhydrous sulfuric acid After magnesium drying, filtration, and concentration, the residue was purified by silica gel column chromatography (gradient elution, eluent ra...

Embodiment 3

[0095] Example 3 Synthesis of Compound C: Icariside II (Icariside II), R 1 = Rham, R 2 =H

[0096] Synthesis of 7-O-tert-butyldimethylsilyl dehydroicariin Xiv: compound dehydroicariin A (1 g, 2.7 mmol) with diisopropylethylamine (1.1 ml, 6.0 mmol) at room temperature Dissolve it in 15ml of dichloromethane, keep stirring at 0°C in an ice bath and add dropwise a solution obtained by dissolving tert-butyldimethylsilyl chloride (450mg, 3.0mmol) in 5ml of dichloromethane, after the addition is complete Remove the ice bath, rise to room temperature, stir for 4 hours, add 50ml of 0.5 mol / L hydrochloric acid, separate the dichloromethane phase, extract the water phase with 3×20ml of dichloromethane, combine the organic phases, and wash with saturated sodium chloride solution After washing, drying over anhydrous magnesium sulfate, filtering and concentrating, silica gel column chromatography purification (gradient elution, eluent ratio is acetone:petroleum ether=5:95-10:90) to obtain...

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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 natural product icariin (English name icariin) compound through total synthesis, which belongs to the technical field of medicine. Background technique [0002] Icariin is a flavonoid glycoside compound in Epimedium genus Berberidaceae. As a nourishing traditional Chinese medicine, Epimedium was first recorded in "Shen Nong’s Herbal Classic" for more than 2,000 years. It is one of the most widely used and longest-standing traditional Chinese medicines in China. genus of plants. Traditional medicine believes that Epimedium has the functions 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 limbs. As one of its main active ingredients, icariin has attracted the attention of many scholars at home and abroad in recent years, and its phar...

Claims

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Application Information

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IPC IPC(8): C07D311/30C07H17/07
Inventor 李毅林朱轶才张洁崔丽妍
Owner 李毅林
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