Chiral gossypol acid with activity on resistance to avian influenza virus and preparation method for same
A technology of avian influenza virus and gossypol acid, applied in the field of chiral gossypol acid and its preparation, can solve the problems of Tamiflu resistance, slow development of anti-avian influenza virus drugs, few varieties, etc., and achieve strong inhibitory effect Effect
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Embodiment 1
[0041] L-gossypol acid ( I ), the specific steps are as follows:
[0042] 1. Preparation of L-gossypol ((-)-gossypol) (see publication number CN 101020626A, date of publication is August 22, 2007, invention name is high-purity optically active (-)-gossypol or (+ )-Chinese patent of the preparation method of gossypol), as follows:
[0043] 1.1 Preparation of (-)-gossypol-L-tryptophan methyl ester Schiff base and (+)-gossypol-L-tryptophan methyl ester Schiff base
[0044] (a) Preparation of (-)-gossypol-L-tryptophan methyl ester Schiff base:
[0045] Weigh 15.736g (61.776×10 -3 mol) L-tryptophan methyl ester hydrochloride was dissolved in 200ml ethanol, and 2.471g (61.776×10 -3 mol) NaOH, after dissolved, add 16.017g (30.888×10 -3 mol) gossypol, reacted at 45°C for 4h. After the reaction was complete, the system was turbid, and a yellow solid precipitated out. Suction filtration, the yellow solid was washed with ethanol and dried to obtain 6.453 g of (-)-gossypol-L-tryptop...
Embodiment 2
[0058] The preparation of D-gossypol acid, concrete steps are as follows:
[0059] 1. Preparation of dextro-gossypol ((+)-gossypol) (see publication number CN 101020626A, date of publication is August 22, 2007, invention name is high-purity optically active (-)-gossypol or ( +)-Chinese patent of the preparation method of gossypol), as follows:
[0060] Weigh 3.00g (3.268×10 -3 mol)(+)-gossypol-L-tryptophan methyl ester Schiff base (see step 1.1(b) in Example 1 for its preparation) was dissolved in 200ml of ether, added 12ml of glacial acetic acid, at 50°C Stir. Add 100 μL of concentrated hydrochloric acid (hydrochloric acid concentration is 37%), stir for 2 hours, after the reaction is over, filter to remove the insoluble white powder, wash the ether layer with water until pH ≈ 7, dry it with anhydrous sodium sulfate, concentrate the ether solution, add petroleum ether to crystallize Precipitate, dry to obtain 1.16g yellow powder D-gossypol ((+)-gossypol), yield 68.5%. [α]...
Embodiment 3
[0070] Anti-avian influenza virus experiment of L-gossyphenolic acid and D-gossyphenolic acid
[0071] 1. Experimental materials
[0072] (1) Virus: H 5 N1 The virus strain is A / VietNam / 1194 / 2004, and its titer was 4×10 9 PFU / ml, press 10 with culture medium at the time of infection -2 The dilution, namely 40~50PFU / well, was provided by the State Key Laboratory of Virology, Wuhan University.
[0073] (2) Cells: MDCK cells (sourced from China Center for Type Culture Collection, MDCK cells are classic cells for influenza virus plaque experiments), provided by the State Key Laboratory of Virology, Wuhan University.
[0074] (3) Positive control drug: amantadine, provided by the State Key Laboratory of Virology, Wuhan University.
[0075] (4) Sample treatment: Amantadine and the compound of the present invention were prepared into a 10 mg / ml mother solution with DMSO, and diluted with DMSO to form a corresponding gradient when used.
[0076] 2. Experimental method
[0077] 2...
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