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Preparation method of activated vitamin D3 drug CD ring intermediate

A technology of vitamins and intermediates, applied in the field of medicinal chemistry, can solve the problems of low total yield and many side reactions, and achieve the effect of less by-products, high product yield and simple process steps

Active Publication Date: 2017-08-29
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there are existing literature reports on the synthesis method of 25-hydroxy Grundmann's ketone, there are problems such as many side reactions and low overall yield in terms of side chain introduction, secondary hydroxyl protecting group deprotection, etc.

Method used

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  • Preparation method of activated vitamin D3 drug CD ring intermediate
  • Preparation method of activated vitamin D3 drug CD ring intermediate
  • Preparation method of activated vitamin D3 drug CD ring intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Synthesis of Diol Derivative 2

[0061]

[0062] Vitamin D 2 (20.0g, 50.4mmol) was dissolved in a mixed solution of 320mL dichloromethane and 80mL methanol, passed through ozone, stirred and reacted at -78°C for 3h, stopped passing through ozone, and passed through N 2 until the blue color disappears. Add NaBH twice 4 (20.0g, 0.528mol), stop refrigeration, electric stirring overnight. Add saturated NH 4 Cl solution, 1N HCL solution quenched the reaction. Extracted several times with dichloromethane, combined organic phases, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, column chromatography (petroleum ether / ethyl acetate=5 / 1) to obtain diol derivatives 2 (white solid) 7.06g, yield 71%.

[0063] Preparation of 25-hydroxy Grundmann's ketone from diol derivative 2, such as figure 2 as shown,

[0064] (1) Synthesis of compound 3

[0065]

[0066] Diol derivative 2 (12.4g, 58.4mmol) was dissol...

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Abstract

The invention relates to a preparation method of an activated vitamin D3 drug CD ring intermediate. The preparation method comprises the following steps: carrying out iodine substitution on a diol derivative 2 to obtain a compound 3, carrying out hydroxyl reaction on the compound 3 to obtain a compound 4, carrying out Michael addition reaction on the compound 4 to obtain a compound 5, carrying out nucleophilic addition reaction on the compound 5 to obtain a compound 6, carrying out deprotection reaction on the compound 6 to obtain a compound 7, and carrying out oxidation reaction on the compound 7 to obtain a compound 1, namely, the activated vitamin D3 drug CD ring intermediate (25-hydroxy Grundmann's one). The preparation method provided by the invention has the advantages that the steps are simple, the product yield is high, and massive 25-hydroxy Grundmann's one can be prepared.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to an active vitamin D 3 The preparation method of drug-like CD ring intermediate 25-hydroxyl Grundmann's ketone. Background technique [0002] Vitamin D was discovered in cod in 1936 3 . Vitamin D was later discovered 3 Its physiological function is to promote intestinal calcium absorption, induce bone calcium and phosphorus deposition and prevent rickets. Vitamin D in the body 3 It is converted from 7-dehydrocholesterol in the epidermis and skin tissue, or from food. Under the action of liver hydroxylase, vitamin D 3 The 25th position of the side chain is hydroxylated, and under the action of kidney hydroxylase, the 1st position of the A ring is hydroxylated and converted into active vitamin D 3 (calcitriol), ie 1α,25-(OH) 2 D. 3 , is vitamin D 3 The basic form that plays a physiological role. Vitamin D receptors exist not only in the small intestine, bones, and kidne...

Claims

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Application Information

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IPC IPC(8): C07C45/29C07C49/513
CPCC07C29/128C07C29/62C07C45/29C07F7/1804C07F7/188C07F7/1892C07C49/513C07C35/32C07C35/52
Inventor 刘兆鹏粟肖为
Owner SHANDONG UNIV
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