Preparation method of anchor point dehydrogenated diisoeugenol_Kain Industrial Additive

Background and overview^[1]

Nutmeg, the dried seed kernel of the Myristica fragransHoutt. plant of the Myristicaceae family. It is mainly produced in Malaysia and Indonesia; it is also cultivated in Guangdong, Guangxi and Yunnan in my country. This species is a famous tropical spice and medicinal plant. Harvest when the fruits are ripe in winter and spring. Its seeds are used as medicine to treat diarrhea, cold dysentery, epigastric cold pain, vomiting, etc.; external use can be used as a parasite repellent to treat rheumatic pain, etc. Dehydrodiisoeugenol is the characteristic chemical component of nutmeg. Its English name is Dehydrodiisoeugenol, its molecular formula is C20H22O4+, and its molecular weight is 326.39. It belongs to the lignan class of compounds. Dehydrodiisoeugenol is a characteristic chemical component of nutmeg. The 2010 edition of the Chinese Pharmacopoeia uses dehydrodiisoeugenol as the only basis for identifying nutmeg medicinal materials.

However, after reviewing a large number of literature, it was found that there are currently only literature introductions on the conventional crystallization of dehydrodiisoeugenol, but they cannot separate high-purity dehydrodiisoeugenol well. Therefore, so far, there is no mature process report for preparing the active ingredient dehydrodiisoeugenol from nutmeg.

Preparation^[2]

A method for separation and purification of dehydrogenated diisoeugenol monomer, which is obtained by using nutmeg as raw material for extraction, extraction, silica gel column separation and preparation and recovery. The specific process steps are as follows:

A. Extraction: Crush the dried nutmeg into coarse powder, add an ethanol solution with a mass percentage concentration of 95% according to the volume ratio of medicinal material weight to ethanol of 1:8~10, heat and reflux for extraction, and extract a total of 3 times. For 2 to 3 hours each time, the extract is filtered, the filtrate is combined, concentrated to recover ethanol, and a concentrated extract is obtained for extraction in the next step;

B. Extraction: Add 1 times the volume of water (80°C) to the volume of the concentrated extract obtained in step A to dilute, then add 1 times the volume of the diluted extract aqueous solution with ethyl acetate for extraction, and extract 3 times in total. , combine the ethyl acetate layers, use a rotary evaporator at 55°C to concentrate to a flowing extract, add 5 times the weight of the obtained extract to 60-80 mesh silica gel, mix and dry, and prepare for silica gel column separation;

C. Silica gel column separation: According to the weight of the mixed sample obtained in step B, weigh 10 times the weight of 200-300 mesh silica gel, mix it well with the eluent, put it into a glass chromatography column, and use the eluent to settle. Until the flow rate is constant; put the dried silica gel sample in step B into a glass chromatography column, elute with an eluent, collect the dehydrodiisoeugenol product segment according to TLC detection, and recover the eluent to obtain white floc. solid; the eluent is composed of petroleum ether (60-90°C) and ethyl acetate in a volume ratio of 6:1.

D. High-performance liquid phase preparation and separation: take the solid obtained in step C, dissolve it with dimethylformamide (DMF) in a 1g:10ml solution, filter, and perform the preparation and separation of dehydrodiisoeugenol monomer, UV The detector is monitored online, and the preparation fraction solution of dehydrodiisoeugenol monomer is collected in a targeted manner to obtain a dehydrodiisoeugenol monomer solution; the high-performance liquid phase separation uses a chromatographic column with a C18 filler; the mobile phase composition is: : According to the volume ratio, methanol: water = 75:25, the detection wavelength is 274nm.

E. Product recovery: Heat the dehydrodiisoeugenol monomer solution separated by high-efficiency preparative liquid chromatography in step D to recover methanol. Dehydrodiisoeugenol will precipitate into flocculent crystals in the remaining liquid. Use Filter through a funnel, and place the obtained flocculent crystals into an oven to dry at 55°C to obtain the dehydrodiisoeugenol monomer product.

Main reference materials

[1] Preparation process of nutmeg reference substance dehydrodiisoeugenol

[2]CN201110420161.2 A method for separation and purification of dehydrodiisoeugenol monomer