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Synthesis method of racemic bornyl beta-(3,4-dihydroxyphenyl)-alpha-hydroxypropionate

A technology of borneyl danshensu and danshensu, which is applied in the field of drug synthesis, can solve problems such as the need to increase the yield, and achieve the effects of easy processing or recycling, reduced production costs, and high product yield and purity

Active Publication Date: 2014-09-10
NORTHWEST UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In view of the industrial cost problem of this method, the yield still needs to be improved

Method used

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  • Synthesis method of racemic bornyl beta-(3,4-dihydroxyphenyl)-alpha-hydroxypropionate
  • Synthesis method of racemic bornyl beta-(3,4-dihydroxyphenyl)-alpha-hydroxypropionate
  • Synthesis method of racemic bornyl beta-(3,4-dihydroxyphenyl)-alpha-hydroxypropionate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] (1) Synthesis of 3,4-dibenzyloxybenzaldehyde:

[0060] Dissolve 55.2g (0.40mol) of protocatechualdehyde in 600mL of N,N-dimethylformamide, slowly add 116.0g (0.92mol) of benzyl chloride, and weigh anhydrous K 2 CO 3 165.6g (1.2mol) was added to it, stirred and reacted at room temperature for 2 hours, then added K 2 CO 3 55.2g (0.40mol), heated at 130°C for 2 hours, cooled to room temperature, filtered with suction, the filtrate was added to ice water, acidified with dilute hydrochloric acid to produce a yellow precipitate, filtered with suction, washed with ice water to obtain 3,4-dibenzyloxy 122.1 g of benzaldehyde, the yield was 96%.

[0061] (2) Synthesis of Bornyl Chloroacetate:

[0062] Add 400mL of dichloromethane, 77.2g (0.5mol) of borneol, 50.5g (0.5mol) of triethylamine into the reaction vessel, add 56.4g (0.5mol) of chloroacetyl chloride at 0°C, and stir the reaction at room temperature for 3 hours. Add 200mL of water to the solution, wash with 200mL of s...

Embodiment 2

[0076] This embodiment differs from Embodiment 1 in that:

[0077] (1) Synthesis of 3-(3,4-dibenzyloxyphenyl)bornyl glycidate:

[0078] Dissolve 12.2 g (0.225 mol) of sodium methoxide in 150 mL of methanol to obtain solution 1;

[0079] Dissolve 47.7g (0.15mol) of 3,4-dibenzyloxybenzaldehyde and 48.4g (0.21mol) of bornyl chloroacetate in 200mL of dioxane to obtain solution 2;

[0080] Within 1 hour, drop solution 2 into solution 1, keep the reaction temperature at 5-10°C, after the dropwise addition, slowly warm up to room temperature, stir overnight, add the reaction solution into 200mL of ice water, adjust the hydrochloric acid to neutral, Extracted with dichloromethane (200mL×4), combined the organic phases, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and recrystallized the crude product with ethanol / petroleum ether to obtain 37.6g of off-white solid with a yield of 75%.

[0081] (2) Synthesis of Danshensu Bornyl Ester:

[0082] Dissolve 25....

Embodiment 3

[0084] This embodiment differs from Embodiment 1 in that:

[0085] (1) Synthesis of 3-(3,4-dibenzyloxyphenyl)bornyl glycidate:

[0086] Dissolve 21.6 g (0.225 mol) of sodium tert-butoxide in 150 mL of tert-butanol to obtain solution 1;

[0087]Dissolve 47.7g (0.15mol) of 3,4-dibenzyloxybenzaldehyde and 34.6g (0.15mol) of bornyl chloroacetate in 150mL of dioxane to obtain solution 2;

[0088] Within 1 hour, drop solution 2 into solution 1, keep the reaction temperature at 5-10°C, after the dropwise addition, slowly warm up to room temperature, stir overnight, add the reaction solution into 200mL of ice water, adjust the hydrochloric acid to neutral, Extract with dichloromethane (200 mL×4), combine the organic phases, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and recrystallize the crude product with ethanol / petroleum ether to obtain 49.2 g of off-white solid, with a yield of 64%.

[0089] (2) Synthesis of Danshensu Bornyl Ester:

[0090] Dissolve ...

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Abstract

The invention relates to a synthesis method of racemic bornyl beta-(3,4-dihydroxyphenyl)-alpha-hydroxypropionate. The method comprises the following steps: carrying out Darzens epoxidation on an initial raw material benzyl protected protocatechualdehyde, and carrying out palladium catalyst / hydrogen or Raney nickel / hydrogen catalytic reduction to obtain racemic bornyl beta-(3,4-dihydroxyphenyl)-alpha-hydroxypropionate. The purity and the yield of a product synthesized by adopting the method reach 98% and 48.6% respectively. The synthesis method has the advantages of simple and easily available raw material, short route, high yield, and suitableness for large scale industrialized production.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a synthesis method of danshensubornyl ester, a medicine that can be used for treating or preventing cardiovascular and cerebrovascular diseases. Background technique [0002] Hexdanshensu Bornyl Ester, the chemical name is (±)-3′,4′-dihydroxyphenyl-2-hydroxybornyl propionate. Based on the compatibility principle of "drugs", it is designed by combining the active ingredient Danshensu of "Junyao" Danshen and "Shiyao" borneol in the form of ester bonds. Danshensubornyl ester has anti-atherosclerosis, anti-cardiocerebral ischemia, lower blood pressure, improve cardiac diastolic function and so on. [0003] Chinese patent application (publication number: CN1868998A) discloses a reaction of protocatechualdehyde and acetylglycine to obtain 2-methyl-4-(3,4-diacetoxybenzylidene) oxazolone, which is obtained through ring opening Obtain (3,4-diacetoxybenzylidene)-N-...

Claims

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Application Information

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IPC IPC(8): C07C69/732C07C67/327C07C67/31C07C69/63C07C67/14
CPCC07C45/64C07C67/14C07C67/31C07C67/327C07C67/343C07C2602/42C07C69/732C07C69/734C07C47/575C07C69/63
Inventor 郑晓晖白亚军张群正南叶飞秦方刚刘佩方佳成
Owner NORTHWEST UNIV
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