2-Methyl-l,4-naphthoquinone, menadione

Vitamin K3 (2-methyl-l,4-naphthoquinone, Menadione, Menaphthone) [58-27-5] M 172.2, m 105-106", 105-107". Recrystd from 95% EtOH, or MeOH after filtration. Bright yellow crystals which are decomposed by light. Solubility in EtOH is 1.7% and in C6H6 it is 10%. It IRRITATES the mucous membranes and skin. [Fieser J Biol Chem 133 391 1940.]... 

Cyclohexene epoxide, cyclohexen-l-ol, cyclohexen-l-one 2-Cyclohexene-1 -one, 2-cyclohexene-1 -ol 2-Methyl-l, 4-naphthoquinone (menadione, or vitamin K3)... 

Thus, in general catalytic oxidations with molecular oxygen are not applicable to more complicated, less volatile molecules. For reactions in the liquid phase catalytic oxygen transfer constitutes a useful alternative that combines the advantages of stoichiometric oxidants (high selectivities and broad scope) with those of catalytic oxidation with 02 (inexpensive reagent and environmentally acceptable) [3,4], A reaction of commercial interest, to illustrate the point, is the oxidation of 2-methylnaphthalene to 2-methyl-l,4-naphthoquinone (menadione), an intermediate for vitamin K. Traditionally this oxidation was carried out with stoichiometric quantities of chromium trioxide in sulfuric acid and produced 18 kg... 

Monney, L., Ohvier, R., Otter, 1., Jansen, B., Poirier, GG., and Bomer, C., 1998, Role ofan acidic compartment in tumor-necrosis-factor-a-induced production of ceramide, activation of caspase-3 and apoptosis. Eur. J. Biochem. 251 295-303 Morrison, H., Jemstrom, B., Nordenskjdld, M., Thor, H., and Orrenius, S., 1984, Induction of DNA damage by menadione (2-methyl-l,4-naphthoquinone) in primary cultures of rat hepatocytes. Biochem. Pharmacol. 33 1763-1769 Neuzil, J., Svensson, 1., Weber, T, Weber, C., and Brunk, U.T., 1999, alpha-tocopheryl succinate-induced apoptosis in Jurkat T cells involves caspase-3 activation, and both lysosomal and mitochondrial destabilisation. FEES Lett. 445 295-300 Ngo, E.O., Nutter, L.M., Sura, T., and Gutierrez, P. L., 1998, Induction ofp53 by the... 

Chemical structure (Figure 5). Derivatives of naphthoquinone natural forms contain an unsaturated isoprenoid side chain on C-3 parent compound 2-methyl-1,4-naphthoquinone (menadione, not thought to occur naturally) green plants contain 2-methyl-3-phytyl-l,4-naphthoquinone (phylloquinone, vitamin Ki) with one double bond in the side chain. 

Release of Ca from intact rat liver mitochondria can be induced by oxidation of mitochondrial pyridine nucleotides. This was first shown by the group of Lehninger [8] who oxidized mitochondrial pyridine nucleotides with acetoacetate or oxaloacetate at the level of the citric add cycle. Our group [9 used hydroperoxides, known to be produced by the respiratory chain of mitochondria and to be linked to pyridine nucleotides by glutathione peroxidase and reductase, to induce Ca release and oxidation of pyridine nucleotides. Orrenius and co-workers employed [10] menadione (2-methyl-l, 4-naphthoquinone) to induce pyridine nucleotide oxidation and Ca release. The latter... 

A number of forms of vitamin K are known to exist. All compoimds exhibiting vitamin K activity possess a 2-methyl-l,4-naphthoquinone ring (menadione), which animals are unable to synthesise but plants and bacteria can. 

Menadione, or vitamin K3 (VK3), is the synonym for 2-methyl-l,4-naphthoquinone, and does not occur in nature. It has to be synthesized, and acts as an intermediate in synthesis of K vitamins. VK3, as a provitamin, can be transformed to MK4 by micro-organisms. Menadione has been shown to exhibit antitumor activity in rodent and human tumor cells (6-9). A water-soluble form of the provitamin VK3 (menadione sodium bisulfite, MSB see Structures 6 and 7 in Fig. 1) is often added to animal feed, and after treatment with aqueous Na2C03 (destroying the bisulfite salt) and/or irradiation with UV-radiation (10), it can be chromatographed and analyzed in usual ways. 

The K homologues [1] are a family of 2-methyl-l,4-naphthoquinones possessing cofactor activity for y-glutamylcarboxylase and differ in the side chain attached at C3. Phylloquinone (vitamin Ki) has a phytyl side chain and occurs in green plants. Vitamin K2 includes a group of compounds s)mthesized by bacteria and characterized by a polyisoprene side chain each of them is designated menaquinone-n (MK-n, with n from 4 to 13) according to the number of isoprenyl units. Menadione (vitamin K3), menadiol (vitamin K4), and vitamin Ki(2s) are synthetic forms [1,4]. 

VITAMIN K. Sometimes referred to as the antihemmorhagic vitamin, and. earlier in its development, the prothrombin factor or Koagulations-vitamin, vitamin Kis a substituted derivative of naphthoquinone and occurs in several forms. The designationphylloquinone. or Ki, refers to 2-methyl-3-phytyl-l,4 naphthoquinone the designations famoquinone and prertyl-menaquinone, or K2, refer to 2-difarnesyl-3-methyl-1, 4-naphthoquinone. Menadione, sometimes called oil-soluble vitamin K3, is 2-methyl-1,4-naphthoquinone. The structure of phylloquinone is ... 

Vitamin K activity is associated with at least two distinct natural substances, designated as vitamin K, and vitamin Kj. Vitamin K or phylloquinone (phytonadione) is 2-methyl-3-phytyl-l,4-naphthoquinone it is found in plants and is the only natural vitamin K available for therapeutic use. Vitamin K is actually a series of compounds (the mena-quinones) in which the phytyl side chain of phylloquinone has been replaced by a side chain built up of 2 to 13 prenyl units. Considerable synthesis of menaquinones occurs in Gram-positive bacteria indeed, intestinal flora synthesize the large amounts of vitamin K contained in human and animal feces. In animals menaquinone-4 can be synthesized from the vitamin precursor menadione (2-methyl-l,4-naphtho-quinone), or vitamin Kj. Depending on the bioassay system used, menadione is at least as active on a molar basis as phylloquinone. 

Figure 1 Structural formulas of some K vitamers (1) vitamin Ki(20), (VKl), phylloquinone or 2-methyl-3-eicosa-2 -ene-l,4-naphthoquinone (2) trideuterium labeled VKl, VKl-rfj, 2-methyl-rf3-3-eicosa-2 -ene-1,4-naphthoquinone as internal standard for GC-MS analysis (3) VKl-epoxide (4) menaquinone-4, MK4, 2-methyl-3-tetraprenyl-l,4-naph-thoquinone, as an example of the MKn series (5) VKl-heptafluorobutyryl ester after reductive acylation of VKl (6) menadione, vitamin K3 (VK3), or 2-methyl-1,4-naphthoqui-none (7) menadione sodium bisulfite (MSB), water-soluble form of VK3.

Vitamin K3 (menadione, MK-0,2-methyl-1,4-naphthoquinone) is a synthetic substance. The product of menadione reduction, known as menadiol (2-methylnaphthalene-l,4-diol), and derived compounds, such as the fat-soluble menadiol diacetate or menadiol dibutyrate and the water-soluble sodium salt of menadiol diphosphate, are referred to as vitamin K4. Activity of vitamin K was also detected in the synthetic monoamino analogues and diamino analogues of menadiol, for example, in l-amino-4-hydroxy-3-methylnaphthalene (vitamin K5), l,4-diamino-2-methylnaphthalene (vitamin Kg) and l-amino-4-hydroxy-2-methylnaphthalene (vitamin K ). 

Vitamin K (antihemorrhagic vitamin, phyUoquinone) is a naphthoquinone with an isoprenoid side chain. The side chain can be synthesized by the mammalian organism (Chapt. XIV-1, 9). For this reason, menadione (= 2-methyl-l,4-naphtho-quinone) has phyUoquinone activity. Biochemically, vitamin K seems to be involved as a redox catalyst in the respiratory chain (Chapt. X-4), but the question is not yet solved. 

As hydroxyl or hydroxyl-like radicals are produced by the superoxide-driven Fenton reaction, superoxide overproduction must also occur in thalassemic cells. First, it has been shown by Grinberg et al. [382], who demonstrated that thalassemic erythrocytes produced the enhanced amount of superoxide in comparison with normal cells in the presence of prooxidant antimalarial drug primaquine. Later on, it has been found that the production of superoxide and free radical-mediated damage (measured through the MetHb/Hb ratio) was much higher in thalassemic erythrocytes even in the absence of prooxidants, although quinones (menadione, l,4-naphthoquinone-2-methyl-3-sulfonate) and primaquine further increased oxidative stress [383]. Overproduction of superoxide was also observed in thalassemic leukocytes [384]. 

Other natural naphthoquinones, such as menadione, 1,4-naphthoquinone, 3-methyl-1,4-naphthoquinone and 2,3-dimethoxy-l,4-naphthoquinone... 

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