Preparation method for alfacalcidol

Abstract

The invention relates to a preparation method for a compound, in particular to the preparation method for separating and purifying alfacalcidol. Aiming at the deficiencies of the conventional preparation technology, the invention provides a novel method for preparing alfacalcidol with good yield and high purity. The preparation method comprises the steps as follows: taking vitamin D3 as a raw material; removing most of trans-isomer impurities generated after chemical reaction by utilizing Diels-Alder reaction; and refining and purifying by preparative high pressure liquid chromatography to prepare high-purity alfacalcidol. According to the preparation method, the reaction conditions are moderate, the yield is high, and the purity of alfacalcidol reaches up to 99.5%.

Description

technical field [0001] The invention relates to a preparation method of a compound, in particular to a preparation method for the separation and purification of alfacalcidol, which belongs to the field of drug synthesis. (Technical Field of Organic Compound Synthesis) Background technique [0002] Alfacalcidol, chemical name: 9,10-cyclocholesta-5Z,7E,10(19)-triene-1a,3b-diol. The chemical formula is: [0003] [0004] Alfacalcidol is a fat-soluble sterol in vitamin D compounds, which is a kind of substance involved in the stability of the internal environment of calcium and phosphorus and the mineralization process of bone. Alfacalcidol is Vitamin D 3 Active vitamin D converted in the body by the action of 1α-hydroxylase in the kidneys. [0005] Alfacalcidol 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 caus...

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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 samples are few, and alfacalcidol has no obvious positive and negative electrodes, so it is not suitable for the separation of alfacalcidol

Among planar chromatography, thin-layer chromatography is more suitable for the separation of alfacalcidol. Thin-layer chromatography has the advantages of large sample loading and short separation time, and its equipment is simple, easy to operate, and sample pretreatment is simple, but the separation The effect is poor, the error is large, the stereoisomers cannot be separated, and the recovery 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 , which avoids 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 separation cost is high, and it is easy to cause environmental pollution, which is not suitable for large-scale production (Yu Shilin .University Liquid Chromatography Method and Application. Beijing: Chemical Industry Press, 2000)

[0008] In summary, the existing separation methods have certain limitations, such as low production capacity, long cycle time, low yield, and it is difficult to effectively obtain pure alfacalcidol. A more reasonable and low-cost method should be designed. Preparation method in line with industrial production

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