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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 trivial details, increased cost, low yield and the like, and achieves the effects of avoiding hydrazinolysis reaction and easy operation.

Active Publication Date: 2011-11-23
江苏宁录科技股份有限公司
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  • Abstract
  • Description
  • Claims
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AI Technical Summary

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
Comparison scheme
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 invention provides a synthetic method for sulforaphane and belongs to the field of drug synthesis. The method comprises the following steps that: after amino in 4-amino-1-butanol is protected by Boc groups, hydroxy in 4-amino-1-butanol is changed into methanesulfonyl ester by methanesulfonyl chloride, and then the resultant reacts with sodium methyl mercaptide to produce 4-methylthio butyl-1-tert-butoxycarbonylamide; Boc protective groups are removed under acidic condition to obtain 4-methylthio-1-butylamine; 4-methylthio-1-butylamine reacts with carbon disulfide for one hour in the presence of triethylamine and p-toluenesulfonyl chloride is added for treatment for half an hour to produce 4-methylthio butyl-1-isothiocyanate; and at last 4-methylthio butyl-1-isothiocyanate is oxidized by m-CPBA to produce sulforaphane. According to the invention, complex hydrazinolysis of phthalimide in aftertreatment is avoided and toxic thiophosgene is not needed in the preparation of isothiocyanate; overall yield of sulforaphane is 64%, substantially higher than the overall yield of 8% reported in literature; the whole preparation process is simple and time-saving 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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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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