Preparation method of calcitriol

Abstract

The invention relates to a preparation method of calcitriol which is a compound material, belonging to the technical field of preparation of drug synthesis and organic compound synthesis. In the invention, the calcifediol is taken as raw material, a majority of produced impurities in the chemical reaction process are removed through medium-pressure liquid phase chromatography, wherein calcifediol carried out sulfonylation and ring closing on toluene, and the medium-pressure liquid phase chromatography is used for removing the impurities; products carry out oxidation reaction, medium-pressure chromatographic column separates and removes the impurities, ring opening is carried out, medium-pressure liquid phase is added for coarsely separating stereoisomeride, and at last the products separated by high-pressure liquid phase chromatography is hydrolyzed and refined to obtain the calcitriol. The invention is reasonably selected, comprehensively applies the advantages of the medium and high pressure liquid phase chromatography, has simple detaching method, can effectively remove the impurities, thoroughly separates the stereoisomeride, has high purity of the calcitriol obtained from separation, has a productive rate of 40 percent, high yield and low cost, shortens production period, is suitable for industrial scale, has application prospect, and provides a time-saving, economic and efficient method for the separation and the preparation of chiral compounds.

Description

Technical field: [0001] The invention relates to a method for preparing a compound raw material calcitriol, which belongs to the technical field of drug synthesis and organic compound synthesis and preparation. Background technique: [0002] Calcitriol, chemical name: 9,10-cyclocholesta-5Z,7E,10(19)-triene-1α,3β,25-triol. The chemical formula is: [0003] Calcitriol is a drug with multiple chiral centers, a fat-soluble sterol in vitamin D compounds, and a class of substances involved in the stability of the internal environment of calcium and phosphorus and the mineralization of bone. Calcitriol is Vitamin D 3 Active vitamin D converted in the body by 25-hydroxylase in the liver and 1α-hydroxylase in the kidney. Calcitriol can treat postmenopausal women and middle-aged and elderly osteoporosis, hypoparathyroidism, vitamin D 3 Dependent rickets, renal osteodystrophy, and renal rickets, renal bone lesions, and hypoparathyroidism caused by renal failure and other kidney d...

AI Technical Summary

Problems solved by technology

Capillary electrophoresis has a good separation effect, and the separated product is clean, with little pollution and low cost, but its channel is thin, the separated sample is small, and calcitriol has no obvious positive and negative electrodes, so it is not suitable for calcitriol separation

Thin-layer chromatography is more suitable for the separation of calcitriol in planar chromatography. Thin-layer chromatography has the advantages of large sample volume and short separation time, and its equipment is simple, easy to operate, and sample pretreatment is simple, but the separation effect Poor, large error, stereoisomers cannot be completely separated, and the separated product has many impurities, the quantitative steps after separation are complicated, and the sample loss is large during the process

Medium-pressure liquid chromatography and high-performance liquid chromatography are commonly used in column chromatography. Medium-pressure liquid chromatography is relatively simple and has a large amount of sample loading; but its separation effect is poor, the chromatographic column can only be used once, and the column packing operation is complicated , the separation time is long, and it is difficult to solve the separation of complex mixtures

High-pressure liquid chromatography is suitable for organic compounds with high boiling point, non-volatile, unstable and easy to decompose when heated, and large molecular weight; its sensitivity is high, so the separation efficiency is high, the separation speed is fast, and it is not affected by the volatility and thermal stability of the sample. Separation can be carried out at room temperature without high column temperature, the sample will not be destroyed after passing through the chromatographic column, single component can be collected, the separation and purification effect is good, the sample purity after separation is high, and the chromatographic column can also be used repeatedly , avoiding the trouble of packing columns; its disadvantage is that the amount of separated samples is small, so the production cycle is long, and a variety of solvents are used as mobile phases, the analysis cost is high, and it is easy to cause environmental pollution, so it is not suitable for large-scale production (Yu Shilin .University Liquid Chromatography Method and Application. Beijing: Chemical Industry Press, 2000)

[0006] In summary, there are certain limitations in the existing separation and preparation technology methods, which lead to low production capacity, long cycle, low yield, and it is difficult to effectively obtain pure calcitriol

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