Vitamin D oxime derivative and synthetic method and application thereof

A synthesis method and technology of derivatives, applied in the field of medicinal chemistry, can solve problems such as application limitations, and achieve the effects of high yield, easy availability of synthetic raw materials, and mild reaction conditions

Inactive Publication Date: 2015-04-29
NANJING UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, taking it for a long time can cause side effects such as hypercalciuria, hypercalcemia

Method used

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  • Vitamin D oxime derivative and synthetic method and application thereof
  • Vitamin D oxime derivative and synthetic method and application thereof
  • Vitamin D oxime derivative and synthetic method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Embodiment 1: the synthesis of compound 1.2

[0037] Vitamin D 2 (500mg, 1.26mmol), aluminum isopropoxide (510mg) were dissolved in toluene, acetone (50mL) was added, and the reaction was refluxed. After TLC traced the reaction, dilute hydrochloric acid was slowly added to the reaction solution to terminate the reaction, extracted with ethyl acetate, and the organic layer was combined, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The material was subjected to column chromatography (SiO 2 , PE:EA=20:1) to obtain compound 1.2 (0.15 g, 30.17%) as a white solid. 1 H NMR (500MHz, CDCl 3)δ7.26(s,1H),5.92(s,2H),5.41(s,3H),5.33(s,3H),5.29–5.07(m,7H),4.94(s,3H),3.15(t ,J=6.9Hz,6H),2.72(t,J=6.9Hz,7H),2.50(d,J=7.2Hz,10H),2.06–1.91(m,11H),1.85(d,J=6.4Hz ,5H),1.66(t,J=18.6Hz,24H),1.54–1.39(m,15H),1.35–1.20(m,22H),1.01(d,J=6.6Hz,13H),0.92(d, J=6.8Hz,11H),0.84(dd,J=15.9,8.6Hz,22H),0.56(s,10H). 13 C NMR (126MHz,...

Embodiment 2

[0038] Embodiment 2: the synthesis of compound 1.3

[0039] Compound 1.2 (500mg, 1.27mmol), hydroxylamine hydrochloride (106mg, 1.52mmol), and triethylamine (2mL) were dissolved in ethanol, heated to reflux and stirred, and TLC was followed. After the reaction was completed, the reaction mixture was cooled and added to the reaction system Ethyl acetate and water, extracted with ethyl acetate, combined organic layers, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and spin-dried to obtain a yellow oil. After column separation (SiO 2 , PE:EA=20:1) to obtain light yellow viscous 1.3 (270mg, 51.90%). 1 H NMR (500MHz, CDCl 3 )δ7.26(s,1H),6.05(s,2H),5.25–5.11(m,6H),5.05(s,2H),4.97(t,J=7.1Hz,2H),4.11(t,J =7.1Hz,1H),2.69(d,J=7.4Hz,4H),2.49(s,4H),2.05(s,2H),1.46(s,4H),1.32–1.20(m,8H),1.02 (d, J=6.6Hz, 6H), 0.92(d, J=6.9Hz, 7H), 0.83(t, J=7.2Hz, 13H), 0.57(s, 6H). See figure 1 13 C NMR (126MHz, CDCl 3 )δ157.32,144.55,142.47,141.16,1...

Embodiment 3

[0040] Embodiment 3: the synthesis of compound 1.4

[0041] Compound 1.2 (500mg, 1.27mmol), hydroxylamine hydrochloride (106mg, 1.52mmol), and triethylamine (2mL) were dissolved in ethanol, heated to reflux and stirred, and TLC was followed. After the reaction was completed, the reaction mixture was cooled and added to the reaction system Ethyl acetate and water, extracted with ethyl acetate, combined organic layers, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and spin-dried to obtain a yellow oil. After column separation (SiO 2 , PE:EA=20:1) to obtain light yellow viscous 1.4 (170mg, 32.68%). 1 H NMR (500MHz, CDCl 3 )δ6.77(s,1H),5.24(s,1H),5.19(t,J=6.7Hz,2H),5.09(s,1H),4.97(s,1H),3.14(d,J=7.4 Hz,2H),2.65–2.50(m,3H),2.45(dd,J=8.4,5.1Hz,2H),2.10–1.90(m,5H),1.85(d,J=6.3Hz,2H),1.02 (d, J=6.6Hz, 4H), 0.58(s, 4H). See image 3 13 C NMR (126MHz, CDCl 3 )δ153.86,147.04,142.45,141.18,135.63,131.84,116.28,114.72,112.85,77.20,76....

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Abstract

The invention discloses a vitamin D oxime derivative and a synthetic method and an application thereof. The method comprises the following steps: carrying out an oximation reaction between a compound I and hydroxylamine hydrochloride, thereby obtaining two A cyclic oxime derivatives such as (Z)-3-oxime vitamin D2 and (E)-3-oxime vitamin D2 of the vitamin D2 of different configurations; and enabling a compound 1.2 to react with methoxylamine hydrochloride, thereby obtaining two A cyclic oxime ether derivatives such as (Z)-3-methyl oxime ester vitamin D2 and (E)-3-methyl oxime ester vitamin D2 of the vitamin D2 of different configurations. The four vitamin D oxime derivatives have good effects of inhibiting human hepatoma cells Hep G2 and human breast cancer cells MCF-7 and have potential medicinal values.

Description

Technical field: [0001] The invention relates to vitamin D oxime derivatives, a synthesis method and an application thereof, and belongs to the field of medicinal chemistry. Background technique: [0002] Vitamin D compounds are mainly produced by cholesterol compounds (such as: 7-dehydrocholesterol, ergosterol) on the surface of the skin under ultraviolet light. After vitamin D enters the human body, it is transported to the liver through the blood and is metabolized into 25-hydroxyvitamin D by 25-hydroxylase 3 , and then obtain 1α,25-dihydroxyvitamin D through hydroxylation at the 1α-position in the kidney 3 (Its structure is shown in the following formula). 1α,25-Dihydroxyvitamin D 3 It is widely recognized as the bioactive metabolite of vitamin D in humans. It has the function of regulating calcium balance in the human body, the immune system, bone mineralization and the proliferation and differentiation of some cells. These biological functions are regulated by a v...

Claims

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Application Information

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IPC IPC(8): C07C401/00A61P35/00
Inventor 方志杰李红亮
Owner NANJING UNIV OF SCI & TECH
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