CN101066948B - Catalytic hydrogenation and reduction process of coculine for preparing hydrogenated coculine - Google Patents

Abstract

The invention discloses a method for preparing hydrogenated sinomenine by catalytic hydrogenation reduction of sinomenine. The method comprises: (1) using a Pd/C catalyst or a _PtO2 catalyst loaded on activated carbon with 10% Pd, and using hydrogen at 300- Under the pressure of 500psi, in the system where the reaction solvent is water or ethanol, sinomenine is catalytically hydrogenated and reduced to dihydrosinomenine; (2) Rh/Al ₂ O ₃ using 5% Rh loaded on Al ₂ O ₃ powder Catalyst, under the pressure of 300-500 psi of hydrogen, in the system where the reaction solvent is water or ethanol, the catalytic hydrogenation reduction of sinomenine to hydrogenated sinomenine; The surface has high physiological activity.

Description

Method for preparing hydrogenated sinomenine by catalytic hydrogenation reduction of sinomenine

technical field

The invention belongs to chemical pharmacy, and in particular relates to a method for preparing hydrogenated sinomenine by catalytic hydrogenation reduction of sinomenine.

Background technique

Sinomenine is an effective alkaloid isolated herbal medicine extracted from the natural Chinese medicine Qingfengteng (mostly its hydrochloride). The curative effect of sinomenine in treating rheumatoid arthritis is definite, the total effective rate is about 85%, the onset time is 2-3 weeks, and there is obvious improvement after about 1 month. Sinomenine can significantly improve hand and lower limb function, joint morning stiffness time, joint pain, erythrocyte sedimentation rate and rheumatoid factor. The availability is low and the half-life is short. It is particularly worth pointing out that about 1/3 of the patients who use sinomenine cause allergic symptoms of skin itching, which limits the promotion of its application. Using the alkaloid isolated sinomenine as the parent, it is a meaningful work to modify the chemical properties of sinomenine. The hydrogenated sinomenine synthesized by this patent has a relatively high physiological activity through preliminary pharmacological and drug efficacy experiments.

Contents of the invention

The object of the present invention is to provide a method for preparing hydrosinomenine by catalytic hydrogenation reduction of sinomenine. This method contains:

(1) Use a Pd/C catalyst or _PtO2 catalyst with 10% Pd supported on activated carbon, under the pressure of 300-500 psi of hydrogen, in a system where the reaction solvent is water or ethanol, the catalytic hydrogenation reduction of sinomenine to di Hydrogenated sinomenine; as following formula I:

(2) Using a Rh/Al ₂ O ₃ catalyst loaded with 5% Rh on Al ₂ O ₃ powder, under the pressure of 300-500 psi of hydrogen, in a system in which the reaction solvent is water or ethanol, sinomenine is catalytically hydrogenated Reduction into hydrosinomenine as following formula II:

The dosage of the above-mentioned catalyst is 0.5-2% of the sinomenine.

The above reaction temperature can complete the reaction process at room temperature.

The above-mentioned sinomenine is natural isolated sinomenine or natural isolated sinomenine hydrochloride.

The hydrogenated sinomenine synthesized by the invention has a relatively high physiological activity according to the preliminary pharmacological efficacy test.

Instructions attached

Fig. 1 is a crystal structure diagram of hydrosinomenine II of the present invention.

Detailed ways

The technical solutions of the present invention will be further described below in conjunction with the embodiments.

1. Purification of sinomenine

(1) The recrystallization of sinomenine hydrochloride: get 10 grams of sinomenine hydrochloride (content 95%), be dissolved in about 170ml dehydrated alcohol under reflux, then solution is cooled to room temperature, leave standstill, Crystals were separated out and filtered. 9.4 g of white crystals were obtained.

(2) Conversion of sinomenine hydrochloride into sinomenine: Take 2 grams of sinomenine hydrochloride prepared above and dissolve it in about 15 ml of distilled water (pH=7). Slowly adjust the solution system to pH=10 with 15% NH ₃ water, and then extract 4 times with CHCl ₃ (30ml×4). Combine the extracts. The organic phase was dried with anhydrous K ₂ CO ₃ for about 40 min, filtered, and the solvent was removed by rotary evaporation to obtain 1.7 g of white solid.

2. Preparation of dihydrosinomenine I

In a stirred 50ml autoclave, take 1g of sinomenine prepared above, 20ml of ethanol, 0.1g of Pd/C (10% Pd supported on activated carbon) catalyst, pressurize hydrogen to 350psi, and react to the pressure in the reactor at normal temperature After further reduction (about 10 hours), hydrogen gas is released and the reaction is stopped. The solvent is removed to obtain dihydrosinomenine (1) with a yield of 100%.

3. Preparation of Hydrosinomenine II

In a 50ml autoclave with stirring, take 1g of sinomenine hydrochloride prepared above, 15ml of deionized water, 0.1g Rh/Al ₂ O ₃ (5% Rh loaded on Al ₂ O ₃ powder) catalyst, pressurize Hydrogen to 400psi, react at normal temperature until the pressure in the reactor is no longer reduced (about 24 hours), the hydrogen can be released, and the reaction is stopped. The solvent was removed to obtain hydrosinomenine (2) ([α] _D ²⁰ 11.3° (c=1, EtOH)), with a yield of 100%.

Claims (4)

1. a method for preparing hydrogenated sinomenine by catalytic hydrogenation reduction of sinomenine, characterized in that: (1) Use 10% Pd supported on activated carbon as a Pd/C catalyst or _PtO Catalyst, under the pressure of 300 to 500 psi of hydrogen, in a system where the reaction solvent is water, sinomenine is catalytically hydrogenated and reduced to dihydrocyanine Phinerine; as following formula I:

or (2) Use the Rh/Al ₂ O ₃ catalyst with 5% Rh supported on Al ₂ O ₃ powder, under the pressure of 300-500 psi of hydrogen, in the system where the reaction solvent is water, the catalytic hydrogenation reduction of sinomenine into Hydrogenated sinomenine; as following formula II:

2. The method according to claim 1, characterized in that: the dosage of the catalyst is 0.5-2% of sinomenine. 3. The method according to claim 1, characterized in that: said reaction completes the reaction process at room temperature. 4. The method according to claim 1, characterized in that: the above-mentioned sinomenine is natural isolated sinomenine or replaces sinomenine with natural isolated sinomenine hydrochloride.

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