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(-)-Swainsonine preparation method

A technology of swainsonine and its synthesis method, which is applied in the direction of organic chemistry, can solve the problems of difficult gram-level products and limited separation, and achieve the effect of simple route, high yield, and simple operation of the technical route

Active Publication Date: 2015-05-20
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

And unfortunately, the amount of separation is extremely limited, so that the price of swainsonine with a purity of more than 98% in the domestic market is basically around 900-1400 yuan / mg, and it is difficult to buy gram-level products.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Synthesis of (R)-methyl 4-(tert-butyldimethylsilyloxy)-5-hydroxyvalerate (2)

[0022] Dissolve compound 1 (10.0g, 26.6mmol) in 100mL of dichloromethane and 80mL of absolute ethanol, cool to -20°C, add camphorsulfonic acid, naturally rise to room temperature and stir for 5 hours, concentrate and filter through silica gel, ethyl acetate After column chromatography of ester and petroleum ether, a colorless liquid 2 was obtained with a yield of 48%.

[0023] 1 HNMR (300MHz, CDCl 3 )δ: 3.86-3.78(m,1H),3.68(s,3H),3.53(dd,J=4.4,11.2Hz,1H),3.47(dd,J=4.8,11.2Hz,1H),2.46-2.32 (m, 2H), 2.08 (brs, 1H), 1.87-1.82 (m, 2H), 0.9 (s, 9H), 0.1 (s, 6H) ppm.

[0024] Synthesis of (R)-4-(tert-butyldimethylsilyloxy)valerate methyl imine (3)

[0025] Compound 2 (5.0g, 19.1mmol) was dissolved in 100mL of dichloromethane, 2 moles of DMP were added at room temperature and stirred for 4 hours, then filtered with a silica gel funnel, directly concentrated and added tert-butylsulfonamide (3.5g)...

Embodiment 2

[0042] The preparation of compounds 2, 3, 5, 7, and 9 was the same as in Example 1.

[0043] Synthesis of (5R,6S)-5-tert-butyldimethylsilyloxy-6-allylcyclohexylamide (4)

[0044] Compound 3 (1.0g, 2.75mmol) and magnesium bromide (5mL, 1MinTHF) were dissolved in 20mL of tetrahydrofuran, and 8.25mL of 1M allylmagnesium bromide was added at -78°C, and then the temperature was naturally raised for 8 hours. After ammonium chloride quenching, ethyl acetate extraction, drying, concentration, silica gel column purification to obtain viscous liquid 4 (R 2 =CH=CH 2； 519mg, 74%).

Embodiment 3

[0046] The preparation of compounds 2, 3 and 4 was the same as in Example 1.

[0047] Synthesis of 1-((2S,3R)-3-(tert-Butyldimethylsilyloxy)-2-vinylpiperidin-1-yl)prop-2-en-1-one (6)

[0048] Compound 4 (R 2 =CH=CH 2； 1.2g, 4.7mmol) and lithium aluminum hydride (357mg, 9.4mmol) were dissolved in 40mL tetrahydrofuran, stirred at 0-50°C for 4 hours, passed through NaSO 4 .10H 2 Quenched by O, filtered and concentrated, dissolved directly in dichloromethane, cooled to -20°C, added acryloyl chloride (846mg, 9.4mmol) and triethylamine (1.4g, 14.1mmol), stirred overnight at natural temperature, and then dissolved in saturated carbonic acid After sodium hydrogen quenching, dichloromethane extraction, concentrated column chromatography purification, to obtain compound 6 (R 2 =CH=CH 2； X=O) 693mg, the yield is 50%.

[0049] The preparation of compounds 8 and 10 (X=O) was the same as that of compounds 7 and 9 in Example 1.

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Abstract

The present invention belongs to the field of chemical synthesis, and relates to a preparation method of (-)-Swainsonine having anti-cancer activity. According to the present invention, the technical route has characteristics of simple operation, simple route and high yield, and the used reagents are the commonly used reagents; and the cost can be significantly reduced, the 10-100 g-scale preparation can be easily prepared in the laboratory, and the method is suitable for large-scale preparation.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and relates to a preparation method of a natural product swainsonine [(-)-Swainsonine] with anticancer activity. Background technique [0002] Malignant tumors, namely cancer, have become a serious threat to human health after vascular diseases. According to the statistics of the World Health Organization, 11 million people worldwide are diagnosed with cancer every year. At present, among the three methods of treating cancer (surgery, radiotherapy, and chemotherapy), chemotherapy is the fastest-growing and most widely used treatment. However, most of the commercially available anticancer drugs generally have a considerable degree of toxic side effects, drug resistance and short half-life in vivo. Therefore, the research of new antitumor drugs is a challenging and significant research field in life science today. [0003] The natural product swainsonine [(-)-Swainsonine] is a 1,2,8-trihydroxy-...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04
CPCC07D471/04
Inventor 魏邦国司长梅林国强
Owner FUDAN UNIV
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