Scutellarin aglycone derivative as well as preparation method and application thereof
A technology of anthocyanin and derivatives, applied in the field of drug preparation, can solve the problems of general effect, low oral bioavailability, limitation, etc., and achieve significant therapeutic effect, high activity and bioavailability
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[0026] The present application also provides a preparation method of scutellarin aglycon derivatives as shown in (I), including:
[0027] Under the action of an acidic catalyst, 4'-fluoro-5,6,7-trihydroxyflavone, formaldehyde and morpholine as shown in formula (II) are subjected to Mannich reaction in an organic solvent to obtain the formula (I ) scutellarin aglycon derivatives;
[0028]
[0029]
[0030] In the preparation process of scutellarin aglycon derivatives, the 4'-fluoro-5,6,7-trihydroxyflavone shown in formula (II) is specifically prepared according to the following method:
[0031] The compound represented by formula (III) is subjected to oxidative ring closure and demethylation in sequence to obtain 4'-fluoro-5,6,7-trihydroxyflavone;
[0032]
[0033] In the process of oxidative ring closure, SeO can be used 2 / DMSO method, NiCl 2 / Zn / KI method, I 2 / DMSO method or Ni(OAc) 2 / P(Ph) 3 method, in a specific embodiment, what the oxidative ring-closing ...
Embodiment 1
[0046] Example 1: Preparation of 8-morpholine methylene-4'-fluoro-5,6,7-trihydroxyflavone (scutellarin derivative-1)
[0047] Add 9.4 g (26 mmol) of 4′-fluoro-2,4-dimethoxy-3-acetoxy-6-hydroxychalcone, SeO 2 2.9g (13mmol), after DMSO dissolved, reflux and stir in an oil bath at 100°C for 6 hours, cool to room temperature after the reaction was complete, slowly add the system dropwise into 100mL 5% sodium sulfite aqueous solution, stir vigorously, gradually grayish yellow solid precipitated, pumped Filtered, washed with distilled water and dried to obtain 9.2 g of pale yellow solid with a yield of 97%. The crude product was directly used in the next reaction without purification. The reaction formula for this process is as follows:
[0048]
[0049] 25mL round bottom bottle, add 2-(4-fluorophenyl)-5,7-dimethoxy-6-acetoxy-flavone compound 2g prepared in the previous step, under argon protection, 50mL1 equivalent of BF 3 ·Et 2 After O was dissolved, stirred at -10°C for 8...
Embodiment 2
[0053] Example 2: Pharmacological experiments on the therapeutic effect of scutellarin series samples on cerebral ischemia-reperfusion mice
[0054] Test product: Test drug 1: scutellarin Raw material: batch number M1520170606, scutellarin content 99.99%, provided by Kunming Longjin Pharmaceutical Co., Ltd. Test drug 2: scutellarin derivative-1, Prepared by Example 1;
[0055] Positive control drug: nimodipine: product number MB1484-25G, packaging specification: 25G / bottle x 1 bottle, sealed at RT; butylphthalide; aspirin;
[0056] Experimental animals:
[0057] Male C57 mice, weighing 20-25g;
[0058] Modeling method:
[0059] After the mice were deeply anesthetized with 3% pentobarbital sodium (80mg / kg), the skin and subcutaneous tissue of the mice were cut layer by layer in the middle of the neck, the sternocleidomastoid muscle was separated, and the anterior abdomen of the digastric muscle was cut off to expose the For the right common carotid artery (CCA), internal ca...
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