Synthesis method of Teprenone

A synthetic method and technology of teprenone, applied in drug combination, condensation preparation of carbonyl compounds, digestive system, etc.

Inactive Publication Date: 2012-03-21
CHENGDU UNIVERSITY OF TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the configuration of all-trans teprenone is inconsistent with that of teprenone on the market

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] (1) Synthesis of (2E, 6E)-farnesol tosylate

[0024] Add 88.9 grams of (2E, 6E)-farnesol and 40.4 grams of triethylamine into a 1-liter round-bottomed flask, add 500 milliliters of ethyl acetate, heat up to 50 degrees, add 80.0 grams of TsCl under stirring, stop after 5 hours reaction. The reaction mixture was washed with water and saturated brine, the organic phase was dried over anhydrous magnesium sulfate, the filter residue was removed by filtration, and the filtrate was concentrated under reduced pressure to obtain 80-160 g of (2E, 6E)-farnesol tosylate crude product.

[0025] (2) Synthesis of (4E, 8E)-2-acetyl-5,9,13-trimethyltetradec-4,8,12-trienoic acid ethyl ester

[0026] Measure 50 ml of ethyl acetoacetate in a 250 ml round-bottomed flask with a reflux condenser and a magnet, place it on a magnetic stirrer, heat it to a bath temperature of 110-130 degrees under stirring, and put 15 grams of sodium metal into the round-bottomed flask , immediately reacted wi...

Embodiment 2

[0037] (2) Synthesis of (5E, 9E)-farnesyl acetone

[0038]52.4 grams of ethyl acetoacetate was poured into a 250 milliliter round-bottomed flask, placed on a magnetic stirrer, and 9.2 grams of sodium metal was added under stirring at room temperature, and the color of the reaction solution gradually changed from colorless to orange-red thick liquid. After 1 hour, (2E, 6E)-farnesol tosylate crude product was added, and the reaction was continued for 3 hours to obtain (4E, 8E)-2-acetyl-5,9,13-trimethyltetradecyl- The reaction mixture of ethyl 4,8,12-trienoate is directly decarboxylated by alkaline hydrolysis without separation.

[0039] Pour the aqueous solution with 26 grams of KOH into the reaction flask, and stir and reflux the reaction at a bath temperature of 100 degrees. After 5 hours of reaction, the reaction was stopped, and the product floated in the upper layer. Pour directly into 200 ml of diethyl ether for extraction, dry the organic phase with anhydrous potassium ...

Embodiment 3

[0047] Pour an aqueous solution containing 26 grams of KOH into the reaction flask, and stir and reflux at a bath temperature of 100°C. After 5 hours of reaction, the reaction was stopped, and the product floated on the upper layer. Pour directly into methyl tert-butyl ether or isopropyl ether for multiple extractions, dry the organic phase with anhydrous potassium carbonate, filter, and concentrate under reduced pressure to obtain 30-110 grams of light yellow oily liquid (5E, 9E) - farnesyl Acetone crude product.

[0048] (2) Synthesis of (6E, 10E)-geranyllinalool

[0049] The 20% vinyl magnesium chloride of 200 milliliters is poured in the flask that (5E, 9E)-farnesyl acetone crude product is housed, stops reaction after 0.5 hour, pours into a little water quenching reaction, obtains lower floor and is white semi-solid magnesium salt, and the upper layer is an organic solution containing the product. Pour it out, dry it with anhydrous magnesium sulfate, and concentrate th...

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PUM

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Abstract

The invention discloses a synthetic method of teprenone. The synthetic route is to take (2E, 6E)-farnesol as a starting material, and to obtain the teprenone through five steps of reactions sequentially: (1) reaction with sulfuryl chloride or sulfonic anhydride, (2) reaction with acetoacetic acid ester sodium salt, (3) hydrolysis and decarboxylation in an alkaline solution, (4) reaction with vinyl magnesium halide, and (5) reaction with acetoacetate alkyl ester in the presence of a catalyst. The synthetic process can adopt the one-pot method to simplify the process, the second step and the third step, or the first step to the third step, can be finished continuously by two steps or three steps in one pot. In addition, the reaction mixture in the last step can be directly rectified under vacuum for acquiring the teprenone, and the reaction mixtures in other steps only need simple post treatment for respectively obtaining a crude product which is used for the next step of reaction. The preparation method has advantages of simplicity and convenience, easy realization, easy taking of materials, rather mild reaction conditions, and applicable industrialized production.

Description

technical field [0001] The invention relates to a synthesis method of teprenone, which belongs to the field of medicine and fine chemical industry. Background technique [0002] Teprenone (teprenone), the chemical name is 6,10,14,18-tetramethyl-5,9,13,17-nonadecatetraen-2-one, which is (5E, 9E, 13E) and (5Z, 9E, 13E) a mixture of geometric isomers (3:2), a colorless to pale yellow oily liquid with a special aroma. [0003] Teprenone has strong anti-ulcer effect and improvement effect on gastric mucosal lesions for various experimental ulcers and gastric mucosal lesions. Synthesis and secretion, can promote the healing of gastric mucosal injury, can improve the biosynthesis of prostaglandins in gastric mucosa, improve gastric mucosal blood flow, suitable for the treatment of acute gastritis, gastric ulcer, etc. [0004] Teprenone is mainly synthesized through two different synthetic precursors through different synthetic pathways (JP53145922, US4814353): (1) geranyl linaloo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C49/203C07C45/48A61P1/04
Inventor 曾庆乐
Owner CHENGDU UNIVERSITY OF TECHNOLOGY
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