Vitamin K
In 1929, a famous chemist Dam (Denmark) had first discovered and extracted a yellow crystalline substance from animal liver and linseed oil-vitamin K.
Vitamin K is a the indispensable substance for hepatic synthesis of the four kinds of coagulation factors (active clotting factor Ⅱ (prothrombin), coagulation factor Ⅶ, coagulation factors Ⅺ and coagulation factor Ⅹ). Upon a lack of vitamin K1, the above four coagulation factors synthesized in liver synthesis become abnormal protein molecules while their ability to catalyze clotting effect dropped significantly. It is known that vitamin K is the cofactor for the glutamic acid γ-carboxylation. Lack of vitamin K disables the above γ-carboxylation of coagulation factors; in addition, these types of blood coagulation factors will reduce and will cause blood clotting slowing down and bleeding disorders. In addition, it is generally recognized that vitamin K was dissolved in mitochondrial membrane lipids, playing a role of electron transfer. Vitamin K can increase the intestinal motility and secretion property. Lack of vitamin will cause reduction in the tension and contraction of smooth muscle and can also affect the metabolism of some hormones, such as causing delay of the decomposition of glucocorticoids in the liver. It also has similar effects as hydrocortisone. Long-term injection of vitamin K can increase the thyroid and other endocrine activity.
Vitamin K can be divided into two categories with both of them belonging to 2-methyl-1, 4-naphthoquinone derivatives. One class belongs to fat-soluble vitamins, namely vitamin K1 extracted from green plants (such as alfalfa, spinach and other leafy greens, etc.) and vitamin K2 extracted from microorganisms. Vitamin K2 can also be synthesized by human intestinal bacteria (such as E. coli). Vitamin K1 appears as yellow oil-like liquid while K2 appears pale yellow crystals. Both of them have heat resistance property, but are vulnerable to ultraviolet radiation to be destroyed, and therefore should be stored separately. Another class is water-soluble vitamins, namely artificially synthetic vitamin K3 and K4. The most important vitamins are K1 and K2.
Vitamin K appears as oily liquid or solid and is insoluble in water but soluble in oils and organic solvents such as ether. It is chemically stable with heat and acid resistant, but being susceptible to alkali and UV degradation. The human body has a low demand. However, newborn infants are vulnerable to being lack of vitamin K that is an important vitamin for promoting blood clotting and normal bone growth. Dark green vegetables and yogurt are easily available vitamin K supplements obtained from the daily diet. Human has a very small demand for vitamin K but it is needed to maintain the normal function of blood coagulation, reduce heavy bleeding menstrual period, but also to prevent internal bleeding and hemorrhoids. Patients suffering frequent nosebleeds should be take more vitamin K from natural foods.
This information is edited by Xiongfeng Dai from Chemicalbook.
Limited use
Limited GB 14880-94: baby food, 420~475 μg/ku.
Chemical Properties
It appears as yellow to orange transparent viscous liquid and is odorless with the relative density being 0.967 and the refractive index being nD251.525~1.528. It is easily soluble in chloroform, ether and vegetable oil, slightly soluble in ethanol and insoluble in water. It is easily to be decomposed when exposed to light and with being decomposed upon being heated to 120 ℃.
Uses
1. It can be used as food supplements. It can be used in infant foods with the usage amount being 420~475μg/kg.
2. It belongs to vitamin drugs to be used for the prevention and treatment of vitamin K1 deficiency symptom, low thrombin disease and natural newborn hemorrhagic disease.
3. promote blood clotting.
4. promote the synthesis of primary liver thrombin.
5. increase the intestinal motility and secretion function.
Production method
It can be obtained through the following process: o-naphthoquinone is mixed with acetic anhydride to have reduction, acetylation reaction to generate acetylated menadione in the presence of zinc; followed by hydrolysis in ammonia and further condensation reaction with phytol in ether with the catalysis of boron trifluoride to generate dihydro vitamin K1; and finally with hydrolysis, oxidation, purification and refining to derive the products.
Description
Vitamin K
1 is a fat-soluble, dietary nutrient that is essential for the synthesis of proteins important for blood-clotting, bone metabolism, and cell growth. It is found in the photosynthetic tissues of green, leafy plants, where it acts as an electron acceptor forming part of the electron transport chain of Photosystem I. Vitamin K
1 also serves as a precursor to vitamin K
2 and is reported to exhibit anticancer activity in various cell lines.
Chemical Properties
Yellow Oil
Chemical Properties
Phylloquinone is an odorless yellow viscous oil or crystals.
Originator
Mephyton ,MSD ,US ,1941
Uses
Labeled Phytonadione, intended for use as an internal standard for the quantification of Phytonadione by GC- or LC-mass spectrometry.
Uses
Occurs widely in green plants, algae, photosynthetic bacteria.
Definition
ChEBI: Phylloquinone is a member of the class of phylloquinones that consists of 1,4-naphthoquinone having methyl and phytyl groups at positions 2 and 3 respectively. The parent of the class of phylloquinones. It has a role as a cofactor, a plant metabolite and a human metabolite. It is a vitamin K and a member of phylloquinones.
Manufacturing Process
11 parts by weight of 2-methyl-1,4-naphthohydroquinone, 30 parts by volume of water-free dioxane and 1.5 parts by volume of boron trifluoride etherate are heated to 50°C. While agitating and introducing nitrogen, 10 parts by weight of phytol dissolved in 10 parts by volume of dioxane are added in the course of 15 minutes. Thereupon, the dark colored reaction mixture is stirred for 20 additional minutes at 50°C, cooled down and 60 parts by volume of ether are added. The reaction mixture is washed first with water, then with a mixture of 3 parts of N-sodium hydroxide and 2 parts of a 2.5% solution of sodium hydrosulfite and again with water. The aqueous extracts are washed with ether. The ether solutions are collected, dried over sodium sulfate and concentrated, toward the end under reduced pressure.
The waxlike condensation product so obtained is mixed with 60 parts by volume of petroleum ether (boiling limits 30°C to 40°C) and agitated with hydrogen in the presence of a little active palladium lead catalyst (Pd-CaCO3catalyst, the activity of which is reduced by the addition of lead and quinoline). During the operation, the condensation product separates in the form of a voluminous white precipitate. The latter is separated by filtration in the absence of air while adding an inert coarse-grained adsorption agent (for example, aluminum silicate salt for filter purposes), and washed with cooled petroleum ether. Thereupon, the 2-methyl-3-phytyl-1,4-naphthohydroquinone is extracted from the filter cake by means of ether, the ethereal solution is concentrated to 100 parts by volume and the reaction product is oxidized by stirring the solution with 6.6 parts by weight of silver oxide during 30 minutes. The solution is filtered through sodium sulfate, the latter is rinsed with ether and the solvent is evaporated. There are obtained 5.7 parts by weight of 2-methyl-3-phytyl-1,4-naphthoquinone (vitamin K1) in the form of a golden yellow oil.
Therapeutic Function
Prothrombogenic vitamin
General Description
Vitamin K
1, also known as phylloquinone, consists of naphthalenoid and phytyl groups. Phylloquinone is present abundantly in photosynthetic plants and is a major dietary source. It is a fat-soluble vitamin.
Biochem/physiol Actions
Vitamin K1 (Phylloquinone) is a lipid soluble polycyclic aromatic ketone used as a cofactor in the formation of coagulation factors II (prothrombin), VII, IX and X; anticoagulant factors protein C and S and as a cell signaling factor. Vitamin K1 is essential for blood coagulation, bone and vascular metabolism. Phylloquinone from green leafy vegetables and vegetable oil is the most important dietary source of vitamin K for humans.
Clinical Use
Vitamin K deficiency
Antidote to oral anticoagulants
Potential Exposure
Phylloquinone is a dietary component essential for normal biosynthesis of several factors required for clotting of blood; as a therapeutic drug used to correct bleeding tendency; and as a food supplement.
Veterinary Drugs and Treatments
The principal uses of exogenously administered phytonadione is in
the treatment of anticoagulant rodenticide toxicity. It is also used
for treating dicumarol toxicity associated with sweet clover ingestion
in ruminants, sulfaquinoxaline toxicity, and in bleeding disorders
associated with faulty formation of vitamin K-dependent
coagulation factors.
Drug interactions
Potentially hazardous interactions with other drugs
Antagonises effect of coumarins and phenindione.
Metabolism
Phytomenadione is rapidly metabolised to more
polar metabolites and is excreted in bile and urine as
glucuronide and sulphate conjugates.
Shipping
UN3249 Medicine, solid, toxic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials.
Purification Methods
Vitamin K1 is a yellow viscous oil, which can be distilled at high vacuum practically unchanged. It is insoluble in H2O, but soluble in common organic solvents. Store it in the dark under N2 as it is oxygen sensitive. It has 1cm 328 at 248nm. [Fieser et al. J Am Chem Soc 61 2557 1939, Hirschmann et al. J Am Chem Soc 76 4592 1954, Isler & Doebel Helv Chim Acta 27 225 1954, Beilstein 7 IV 2496.]
Incompatibilities
Phylloquinone is photosensitive; decomposes in sunlight and is destroyed by alkali hydroxides and reducing agents such as hydrideds and active metals. Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides.
Waste Disposal
It is inappropriate and possibly dangerous to the environment to dispose of expired or waste drugs and pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quantities of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, double-bagged in plastic, discard in trash. Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
References
[1] STEVEN M PLAZA Davis W L. Vitamin K2 in bone metabolism and osteoporosis.[J]. Alternative Medicine Review, 2005, 10 1: 24-35.
[2] STEFANO SANTABARBARA Michael C W E Peter Heathcote. Modelling of the electron transfer reactions in Photosystem I by electron tunnelling theory: The phylloquinones bound to the PsaA and the PsaB reaction centre subunits of PS I are almost isoenergetic to the iron–sulfur cluster FX[J]. Biochimica et Biophysica Acta-Bioenergetics, 2005, 1708 3: Pages 283-310. DOI:
10.1016/j.bbabio.2005.05.001[3] JOLINE W J BEULENS. The role of menaquinones (vitamin K) in human health.[J]. British Journal of Nutrition, 2013, 110 8: 1357-1368. DOI:
10.1017/s0007114513001013[4] DAVIS W LAMSON Steven M P. The anticancer effects of vitamin K.[J]. Alternative Medicine Review, 2003, 8 3: 303-318.
