Synthetic method for sulforaphane

A technology of sulforaphane and methylthiobutyl, which is applied in the field of synthesis of natural product sulforaphane, can solve the problems of cumbersomeness, high cost, high toxicity, etc., and achieve the effect of avoiding hydrazinolysis reaction and easy operation

Active Publication Date: 2013-07-17
江苏宁录科技股份有限公司
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Problems solved by technology

Existing synthetic method has the defective of three aspects: (1) the productive rate of monoalkylation reaction of phthalimide potassium salt and 1,4-dibromobutane is low (sometimes lower than 30%), mainly is caused by the unavoidable competing reaction of dialkylation
(2) The separation of 4-methylthio-1-butylamine or 4-methylsulfoxide-1-butylamine from the hydrazinolysis reaction is cumbersome and requires strong alkaline Dowex 1X8-200 ion exchange chromatography method (Cancer Research, 2005, 65: 8549-8550), the yield is only 60%, which not only increases the cost, but also limits the large-scale production
Thiophosgene is a low-boiling liquid with a strong pungent smell, high volatility, and high toxicity. Therefore, its use is strictly controlled, and the source is inconvenient

Method used

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  • Synthetic method for sulforaphane
  • Synthetic method for sulforaphane
  • Synthetic method for sulforaphane

Examples

Experimental program
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Effect test

Embodiment 1

[0023] Step 1: 4-tert-butoxyamide-1-butanol 2 preparation of

[0024] Embodiment 1: 4.8 grams (54 millimoles) 4-amino-1-butanols are dissolved in 80 milliliters of tetrahydrofuran, add 12.4 grams (56.7 millimoles) di-tert-butoxycarbonic anhydride (Boc) at room temperature 2 O, stirred for 30 minutes. TLC analysis showed complete disappearance of starting material. After removing the solvent with a rotary evaporator, the residue was separated by flash silica gel column chromatography (eluent: 10% ethyl acetate / n-hexane) to obtain 10.1 g (yield 98%) of 4-tert-butoxyamide-1- Butanol 2。 The product was a colorless transparent liquid, which solidified after standing at room temperature and became a white solid. 1 H NMR (300 MHz, CDCl 3 ): d1.37 (s, 9H), 1.50 (m, 4H), 2.95 (br s, 1H), 3.04 (m, 2H), 3.56 (m, 2H), 4.82 (br s, 1H); 13 C NMR (75 MHz, CDCl 3 ): d26.71, 28.59, 29.87, 40.48, 62.23, 79.30, 156.47; MS (ESI): m / z 190 (M+1), 212 (M+Na).

[0025] 15.2 g (80 mmol) of ...

Embodiment 2

[0033] Step 1: 4-tert-butoxyamide-1-butanol 2 preparation of

[0034] Embodiment 2: 2.4 grams (27 millimoles) of 4-amino-1-butanol are dissolved in 40 milliliters of tetrahydrofuran, and 4.38 grams (20 millimoles) of di-tert-butoxycarbonic anhydride (Boc) are added at room temperature 2 O, stirred for 30 minutes. After removing the solvent with a rotary evaporator, the residue was separated by flash silica gel column chromatography (eluent: 10% ethyl acetate / n-hexane) to obtain 8.36 g (yield 82%) of 4-tert-butoxyamide-1- Butanol 2。 product of 1 H NMR, 13 C NMR and mass spectrum are exactly the same as Example 1.

[0035] Step 2: 4-tert-butoxyamidobutyl-1-methylsulfide 3 preparation of

[0036] Example 2: 15.2 grams (80 mmol) of 4-tert-butoxyamide-1-butanol 2 , a mixture of 16.7 ml (120 mmol) of triethylamine and 240 ml of anhydrous dichloromethane was cooled to 0°C with an ice-water bath, and 6.22 ml (80 mmol) of methanesulfonyl chloride was added dropwise with...

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Abstract

The synthesis method of sulforaphane of the present invention belongs to the field of medicine synthesis. After the amino group in 4-amino-1-butanol is protected by the Boc group, its hydroxyl group is converted into a methylsulfonyl ester by methylsulfonyl chloride, and then reacted with sodium methylthiolate to generate 4-methylthiobutyl-1 - tert-butoxyamide. Under acidic conditions, the Boc protecting group is removed to obtain 4-methylthio-1-butylamine. The latter reacted with carbon disulfide for 1 hour in the presence of triethylamine, and then added p-toluenesulfonyl chloride for half an hour to generate 4-methylthiobutyl-1-thioisocyanate. Finally m-CPBA is oxidized to produce sulforaphane. The present invention avoids the complex phthalimide hydrazinolysis reaction in post-treatment, and does not need to use toxic thiophosgene to prepare thioisocyanate; the total yield is 64%, significantly higher than the total yield of 8% reported in the literature The whole preparation process is easy to operate, saves time, and is suitable for large-scale production.

Description

technical field [0001] The invention relates to a new method for synthesizing natural product sulforaphane, which has cancer prevention and other important biological activities, and belongs to the field of drug synthesis. Background technique [0002] Sulforaphane, also known as sulforaphane, English name is Sulforaphane, CAS number 4478-93-7, molecular formula C 6 h 11 NOS 2 , molecular weight 177.30. Sulforaphane is a thioisocyanate compound, first discovered in 1992 by researchers from Johns Hopkins University in the United States from broccoli sprouts (Proceedings of the National Academy of Sciences, USA. 1992, 89: 2399-2403 ). This compound is also found in other cruciferous vegetables such as kale, bok choy, cauliflower, kohlrabi, mustard greens, radishes, and watercress, usually in the form of glucosinolates. When the plant is broken (such as chewed), glucosinolates are converted into the active ingredient sulforaphane. The sprouts of broccoli and cauliflower...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C331/20
CPCY02P20/55
Inventor 陈新孙小强李正义任杰胡昆
Owner 江苏宁录科技股份有限公司
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