Vitamin K (Vit K), also known as blood coagulation vitamin, is a general term for 2-methyl-1,4-naphthoquinone and its derivatives, including Vit K1, K2, K3, K4 and K5. Among them, Vit K1 and K2 exist naturally, but can also be artificially synthesized; Vit K3 and K4 can only be artificially synthesized. Vit K is an important feed additive and has important applications in the feed sector.
1 Type and nature of Vit K
Vit K, also known as chlorophyll, is a yellow viscous oil that is widely found in green plants and animal livers. Vit K1 is involved in the synthesis of intrahepatic thrombin, which can treat obstructive jaundice, rickets and newborn poultry bleeding. Vit K2 is a polyene compound of isoprene which is pale yellow. The former two are fat-soluble, stable to heat, easily destroyed by alkali, ethanol and light, and need to be protected from light. Vit K3 and Vit K4 are water-soluble, and Vit K3 used in clinical practice is Vit K3 and sodium bisulfite adduct - menaquinone bisulfite. The latter is white crystal, easy to absorb moisture, soluble in ethanol, almost insoluble in benzene and ether. Vit K4 is diacetyl menaquinone condensed with Vit K3 and two molecules of acetic acid; there is also a literature for 4-imino-2-methylnaphthoquinone Vit K4. Vit K3 and Vit K4 are more stable than Vit K1 and Vit K2. Vit K3 has a special pungent odor and is used in the same way as Vit K1, but because Vit K3 is irritating to mucous membranes, it is commonly used as an adduct MSB with sodium bisulfite. Vit K4 is a white or light yellow crystalline powder with an activity of 3-4 times that of Vit K1. After being reacted with serum esterase in vivo, it loses two acetyl groups and is oxidized to Vit K2.
Adult K-sexual bleeding is rare in adult animals, but occasional intestinal mucosal bleeding or oral bleeding occurs in young children. Fish Because there is no mechanism for the synthesis of Vit K in the intestine, long-term feeding of feed lacking Vit K can cause blood spots in the eye, eye or blood vessels. In addition, taking antibiotics, anticoccidial drugs, sulfonamides or feeding moldy feed is also likely to cause Vit K deficiency.
2 Vit K production process
2.1 Vit K original synthesis
2-Methyl-1,4-naphthoquinone (2-MNQ) is an important precursor for the chemical synthesis of Vit K and is therefore called Vit K. Industrial production often uses 2-methylnaphthalene or 2-methyl-1-naphthol as raw materials, and is synthesized by air catalytic oxidation or anodization. 2-Methyl-1-naphthol can be synthesized by catalytic reaction of 1-naphthol with methanol at 280-300 °C. The preparation method of 2-MNQ is mainly based on liquid phase oxidation, that is, 2-MNQ is obtained by oxidizing 2-methylnaphthalene with potassium dichromate or sodium dichromate in an acidic medium. However, in this process, since 2-methylnaphthalene is insoluble in water, the reaction can only be carried out at the interface of two phases, the progress is slow, and the product yield is low; the waste chromium solution produced by oxidation is also likely to pollute the ecological environment.
2.2 Vit K1 production process
Vit K3 is acetylated and then condensed with phytol to obtain Vit K1; phytol can be extracted from silkworm.
2.3 Vit K2 production process
In 1958, ISLER et al first chemically synthesized Vit K2, but the yield was low. In 1994, Hamamura et al. applied for a patent for the production of Vit K2 by the menaquinone-cyclopentadiene addition synthesis method. The method is simple and convenient, and the yield is high. No external reagent and metal catalyst are needed, and alkylation under alkaline conditions can 100% retain the side chain double bond stereo configuration; no redox reaction in the synthesis process, menaquinone It can be kept until the end; the adjuvant cyclopentadiene is easy to recycle and reuse. At room temperature, menaquinone was reacted with cyclopentadiene to give an inner Diels-Alder adduct colorless crystals with a yield of 93%. In the reaction, the non-acid olefinic hydrogen at the α-position of the ruthenium carbonyl group is converted into the α-position hydrogen of the keto group, and the base is substituted for the proton, so that the C-4-α position of the diketone is more easily subjected to the monoalkylation reaction. Since the polyunsaturated side chain does not change under the conditions of the basic alkylation reaction, the method is particularly suitable for the synthesis of Vit K2 in a high yield. Thereafter, the method is further improved, and the corresponding product is obtained under the same reaction conditions using a corresponding alkylating agent in a yield of 80% to 90%, and Vit K2 can be obtained by reversing the Diels-Alder reaction.
2.4 Vit K3 production process
Vit K3 is the most commonly used feed additive. The traditional Vit K3 chemical synthesis process mainly has the following two routes: (1) oxidizing 2-methylnaphthalene by chromic acid or chromic anhydride to obtain Vit K3: oxidizing 2-MN with chromic acid or chromic anhydride to become 2-MNQ, and then Vit K3 can be prepared by sodium hydrogen sulfite addition, the yield of the method can reach about 51%; (2) Vitridinium is cyclized with benzenediene and then oxidized by chromic acid to obtain Vit K3: toluene is added Dissolved in glacial acetic acid, a certain amount of butadiene was introduced at 20 ° C, sealed for 22 h, heated to make the remaining butadiene escape, continue to heat to 110 ° C for about 3 h, and then distilled under reduced pressure. Recover acetic acid, then cool to below 40 ° C, slowly add a mixture of chromic acid and an equal amount of water, keep the temperature at 65 ~ 70 ° C, heat, heat at 70 ~ 80 ° C for 1 h, then generate 2-MNQ, filter, wash Vit K3 is obtained without acid, and then added with sodium bisulfite to obtain Vit K3 application.
2.5 Vit K4 production process
2-MNQ is reduced to 2-methyl 1,4-naphthalenediol by zinc powder in the presence of acetic acid, then acetylated by acetic anhydride under the catalysis of sodium acetate, and refluxed at 138-142 ° C for 2 h to obtain crude Vit. K4. The synthetic route of the method is simple, and the recovery rate is as high as 70% to 74%. In addition, Vit K3 can also be used to produce Vit K4 with acetic acid.
3 Vit K industrial production method prospects
At present, Vit K is mainly produced by chemical synthesis, and there are no reports of biological production. Since the former is prone to environmental pollution, research and attempts to produce Vit K by biological methods such as microbial fermentation have broad prospects. Vit K itself is a metabolite of certain intestinal bacteria. Therefore, it is feasible to produce Vit K by microbial fermentation. This research can be carried out in the future.
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