Menadione

Production

Menadione is synthesized by oxidizing 2-methylnaphthalene with chromic anhydride and then reacting with sodium bisulfite.Reaction: Dissolve 2-methylnaphthalene in glacial acetic acid, stir and cool to below 40°C, slowly add a mixture of chromic anhydride and an equal amount of water, and maintain the temperature at 35-40°C. After the addition, the temperature was kept at 40 °C for 0.5 h, then heated to 70 °C for 45 min, and then heated to 85 °C for 15 min. The reactant was poured into a large amount of water, and menadione was precipitated under constant stirring. After filtering, the filter cake was repeatedly washed with water until the aqueous solution had no sour taste, and then filtered to obtain Menadione. Yield 51%.

Indications

Vitamin K activity is associated with several quinones, including phylloquinone (vitamin K1), menadione (vitamin K3), and a variety of menaquinones (vitamin K2). These quinones promote the synthesis of proteins that are involved in the coagulation of blood.These proteins include prothrombin, factor VII (proconvertin), factor IX (plasma thromboplastin). The vitamin K quinones are obtained from three major sources.Vitamin K is present in various plants, especially green vegetables. The menaquinones that possess vitamin K2 activity are synthesized by bacteria, particularly gram-positive organisms; the bacteria in the gut of animals produce useful quantities of this vitamin.Vitamin K3 is a chemically synthesized quinone that possesses the same activity as vitamin K1.

Preparation

Menadione can be prepared by oxidizing 2-methylnaphthalene with chromic acid or hydrogen peroxide.

Therapeutic Function

Prothrombogenic vitamin

Hazard

Irritant to skin and mucous membranes, especially the alcoholic solution.

Biochem/physiol Actions

Menadione is an oxidative stress inducer.

Pharmacology

The typical role of vitamin K is to maintain normal blood coagulation function. Its role is related to the metabolic processes.

Side effects

Toxicity of vitamin K has not been well defined. Jaundice may occur in a newborn if large dosages of vitamin K are given to the mother before birth. Although kernicterus may result, this can be prevented by using vitamin K.

Safety Profile

Poison by ingestion, intraperitoneal, and subcutaneous routes. Experimental teratogenic effects. Questionable carcinogen with experimental tumorigenic data. Human mutation data reported. When heated to decomposition it emits acrid smoke and irritating fumes.

Purification Methods

Recrystallise it from 95% EtOH, or MeOH after filtration. It forms bright yellow crystals which are decomposed by light. Its solubility in EtOH is 1.7% and in *C6H6 it is 10%. It IRRITATES mucous membranes and skin. [Fieser J Biol Chem 133 391 1940, Beilstein 7 IV 2430.]

General Description

Menadione, also known as Vitamin K3, is a synthetic naphthoquinone derivative that serves as a redox-active compound with applications in antimalarial drug design. Its core structure, particularly when modified with trifluoromethyl groups, has been explored for interacting with glutathione reductase, demonstrating potential as a multitarget-directed antimalarial agent by inhibiting parasitic enzymes and exhibiting potent activity against *Plasmodium falciparum* in vitro. Menadione's redox properties and chemical stability make it a valuable template for developing novel therapeutic agents targeting oxidative stress pathways in malaria parasites.

Chemical properties

It appears as white crystalline or crystalline powder, being almost odorless and hygroscopic. Its color will change in case of light. It is easily soluble in water, slightly soluble in ethanol, but insoluble in ether and benzene.

Application

Menadione is a good hemostatic drug, its main function is to participate in the synthesis of thrombin, promote blood coagulation, can effectively prevent bleeding diseases, and also participate in the mineralization of bones. Menadione is also an important component of feed additives, an indispensable nutrient for the growth and development of livestock, and can also be used as plant growth regulators, promoters, herbicides, etc.

Physical properties

Appearance: phylloquinone is a yellow oil at room temperature, but the other vitamers K are yellow crystals. Solubility: the vitamers K and MK and most forms of menadione are insoluble in water, slightly soluble in ethanol, and readily soluble in ether, chloroform, fats, and oils. Stability: the vitamers K are sensitive to light and alkali, but are relatively stable to heat and oxidizing environments.Menadione, the formal parent compound of the menaquinone series does not occur naturally but is a common synthetic form called menadione (2-methyl-1,4- naphthoquinone). Menadione forms a water-soluble sodium bisulfite addition product, menadione sodium bisulfite, whose practical utility is limited by its instability in complex matrices such as feeds. However, in the presence of excess sodium bisulfite, it crystallizes as a complex with an additional mole of sodium bisulfite (i.e., menadione sodium bisulfite complex), which has greater stability, therefore, is used widely as a supplement to poultry feeds. A third water-soluble compound is menadione pyridinol bisulfite (MPB).

Definition

ChEBI: Menadione is a member of the class of 1,4-naphthoquinones that is 1,4-naphthoquinone which is substituted at position 2 by a methyl group. It is used as a nutritional supplement and for the treatment of hypoprothrombinemia. It has a role as a nutraceutical, a human urinary metabolite, an angiogenesis inhibitor, an EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor and an antineoplastic agent. It is a member of 1,4-naphthoquinones and a vitamin K.

Brand name

Kappaxin (Sterling Winthrop); Kayquinone.