Method for preparing hydroxytyrosol

Abstract

The invention belongs to the field of medicinal synthesis, and particularly relates to a method for preparing hydroxytyrosol, which comprises the following steps of: (1) protecting free hydroxyl groups at 3 and 4 positions, on 3,4-dihydroxy benzaldehyde with benzyl, namely, reacting the 3,4-dihydroxy benzaldehyde with benzyl bromide to prepare 3,4-dibenzyloxybenzaldehyde; (2) reacting N-methylaniline acetonitrile with the 3,4-dibenzyloxybenzaldehyde to prepare 3-(3,4-dibenzyloxyphenyl)-2-(methylphenylamino) acrylonitrile, and hydrolyzing the 3-(3,4-dibenzyloxyphenyl)-2-(methylphenylamino) acrylonitrile under acidic condition to prepare a 3,4-dibenzylosyphenylacetic acid; (3) reducing a carboxyl group of the 3,4-dibenzylosyphenylacetic acid with lithium borohydride, lithium aluminum hydride or sodium borohydride to prepare 3,4-dibenzyloxyphenethyl alcohol; and (4) catalyzing the 3,4-dibenzyloxyphenethyl alcohol with a catalyst palladium / carbon to prepare the hydroxytyrosol. The reagents used in the method are easily obtainable and low in cost, reaction conditions are mild, and the final overall yield of the whole reaction reaches 50 to 60 percent.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a preparation method of hydroxytyrosol. Background technique [0002] Hydroxytyrosol, also known as hydrated tyrosine, 2-(3,4-dihydroxyphenyl)-ethanol, 3,4-dihydroxyphenylethanol, 4-(2-hydroxyethyl)-1,2-benzene Diphenol, whose molecular formula is as follows: [0003] [0004] Hydroxytyrosol was first extracted and isolated from olive oil known as "liquid platinum" and "Mediterranean nectar". It is mainly distributed in olive fruit and olive leaves in nature, but many plants found so far also contain hydroxytyrosol Tyrosol components, such as lilac leaves, Korean clove leaves, etc., all contain the active ingredient of hydroxytyrosol. There are two hydroxyl groups connected to the benzene ring of hydroxytyrosol, which is the main antioxidant active group. Its various biological functions are mostly related to its antioxidant activity as a polyphenol. [0005] Hydro...

AI Technical Summary

Problems solved by technology

[0008] (1) Synthesis of hydroxytyrosol from 3,4-dihydroxyphenylacetic acid: Schopf C et al. used chemical methods to synthesize hydroxytyrosol for the first time. The specific method is mainly to use lithium borohydride to reduce 3,4-dihydroxyphenylacetic acid to obtain hydroxytyrosol Alcohol, the final yield can reach about 40% (see: Schopf, C.; Gottmann, G.; Meisel, E.M.Vber β-(3,4-dioxyphenyl)-athylalkohol.Liebigs Ann.Chem.1949,563,86- 93); In 1983, Baraldi etc. improved the reaction step of above-mentioned method, only adopted two steps and just obtained 66% hydroxytyrosol (referring to: Baraldi PG., Simoni D., Manfredini S., et al.Preparation of 3,4-Dihydroxyl-benzeneethanol: A Reinvestigation. Liebigs Annalen der Chemie, 1983, 4:684-686.); 1999 Capasso in tetrahydrofuran lithium aluminum hydride to reduce 3,4-dihydroxyphenylacetic acid to hydroxytyrosol , and only adopted one-step reaction to obtain 82.8% hydroxytyrosol (seeing: Capasso, R.; Evidente, A.; Schivo, I.; Orru, G.; Marcialis, M.A.; Cristinzo, G.Antibacterial polyphenols from olive oil mill waste waters.J.Appl.Bacteriol.1995,79,393-398.); but the market price of 3,4-dihydroxyphenylacetic acid is relatively high, which greatly increases the production cost invisibly, and has a great impact on industrial production. certain difficulty

[0009] (2) Synthesis of hydroxytyrosol from tyrosol: the raw material of this path is protected, oxidized, and deprotected to synthesize hydroxytyrosol in three steps. This method is relatively simple, but the raw material tyrosol is difficult to obtain, and its market price is relatively high. Invisibly greatly increased production costs, causing certain difficulties to industrialized production (referring to: Roberta B., Enrico M., Maurizio B., etal.Convenient Synthesis of Hydroxytyrosol and Its Lipophilic Derivatives from Tyrosol or Homovanillyl Alcohol.J.Agric. Food Chem. 2008, 56, 8897-8904.)

[0010] In summary, in the prior art, there are starting materials and individual intermediates that are expensive in the chemical synthesis of hydroxytyrosol. Therefore, it is necessary to study a more economical method for the synthesis of hydroxytyrosol

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