Synthesis method of Teprenone

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...