Naphthoquinones menaquinone

The best known isoprenylated quinones are the benzoquinone ubiquinone (157) and the naphthoquinone menaquinone (158), which normally occur in natural tissues as a mixture of homologues (isoprenylogues) with different chain lengths. Analysis of the mixtures of ubiquinone or menaquinone isoprenylogues present in various species has been used in the chemotaxonomic characterization of bacteria. 

The term vitamin K2 was applied to 2-methyl-3-difarnesyl-l,4-naphthoquinone, m.p. 54 C, isolated from putrefied fish meal. It now includes a group of related natural compounds ( menaquinones ), differing in the number of isoprene units in the side chain and in their degree of unsaturation. These quinones also appear to be involved in the electron transport chain and oxidative phosphorylation. 

The shikimate pathway is the major route in the biosynthesis of ubiquinone, menaquinone, phyloquinone, plastoquinone, and various colored naphthoquinones. The early steps of this process are common with the steps involved in the biosynthesis of phenols, flavonoids, and aromatic amino acids. Shikimic acid is formed in several steps from precursors of carbohydrate metabolism. The key intermediate in quinone biosynthesis via the shikimate pathway is the chorismate. In the case of ubiquinones, the chorismate is converted to para-hydoxybenzoate and then, depending on the organism, the process continues with prenylation, decarboxylation, three hydroxy-lations, and three methylation steps. - ... 

The third pathway involved in the quinones biosynthesis is the isoprenoid route. This pathway is primarily important for the formation of prenyl side chains of prenylquinones (ubiquinone, menaquinone, plastoquinones, etc.). The side chains of ubiquinones and prenylated naphthoquinones derive from polyprenyl diphosphates. 

Menaquinone. The incorporation of [2- C]mevalonate and [2- C]-2-methyl-l,4-naphthoquinone into MK-4, normally considered a bacterial quinone, has been demonstrated in marine invertebrates such as crabs and starfish." Incorporation into 2,3-epoxy-MK-4 (163) was also observed. Cell-free extracts have been prepared from Escherichia coli which catalyse the conversion of o-succinylbenzoic acid (164) into l,4-dihydroxy-2-naphthoic acid (165) and menaquinones. In the presence of farnesyl pyrophosphate the major menaquinone produced was MK-3. Genetic studies with mutants of E. coli K12 that require (164) offer support for the generally accepted pathway for MK biosynthesis via (164) and (165)." The enzyme system that catalyses the attachment of the polyprenyl side-chain to 1,4-dihydroxy-2-naphthoic acid to form demethylmenaquinone-9 (166) has been isolated from E. colU ... 

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 ... 

Reaction centers of purple bacteria typically contain three polypeptides, four molecules of bacteriochlorophyll, two bacteriopheophytins, two quinones, and one nonheme iron atom. In some bacterial species, both quinones are ubiquinone. In others, one of the quinones is menaquinone (vitamin K2), a naphthoquinone that resembles ubiquinone in having a long side chain (fig. 15.10). Reaction centers of some species, such as Rhodopseudomonas viridis, also have a cytochrome subunit with four c-type hemes. 

OSB, and 1,4-dihydroxynaphthoic acid, or its diketo tautomer, have been implicated in the biosynthesis of a wide range of plant naphthoquinones and anthraquinones. There are parallels with the later stages of the menaquinone sequence shown in Figure 4.55, or differences according to the plant species concerned. Some of these pathways are illustrated in Figure 4.58. Replacement of the carboxyl function by an isoprenyl substituent is found to proceed via a disubstituted intermediate in Catalpa (Bignoniaceae) and... 

Vitamin K — Fat-soluble vitamin K is a group name for fat-soluble compounds which have in common a methylated naphthoquinone ring structure. Vitamin K is found in nature in two forms - Ki or phylloquinone is found in plants and vitamin K2 or menaquinone can be synthesized by many bacteria. Vitamin K3 (menadione) is a synthetic form of this vitamin. Vitamin K is used... 

Vitamin K is a dietary component essential for the normal biosynthesis of several factors required for clotting of blood. Vitamin Ki (phylloqui-none, phytonadione) is a 2-methyl-3-phytyl-1,4-naphthoquinone, and is the only natural vitamin available for therapeutic use. Vitamin K2 represents a series of compounds (the menaquinones, MK) in which the phytyl side-... 

Vitamin K2 (= Menaquinone)] (naphthoquinone) isolated by Edward Doisy (USA) (Nobel Prize, Medicine, 1943, with Henrik Dam, Vitamin K)... 

As shown in Figure 5.1, compounds with vitaminK activity have a 2-methyl-1,4-naphthoquinone ring. There are two naturally occurring vitamers phylloqui-none (from plants) has a phytyl side chain, whereas the menaquinones (from bacteria) have a polyisoprenyl side chain, with up to 15 isoprenyl units (most commonly 6 to 10), shown by menaquinone- n. Bacteria also form a variety of... 

The method could be applied to the synthesis of many natural benzo- and naphthoquinones. The masked quinone (146), which may serve as a general precursor to the menaquinones, was prepared and isoprenylated by a similar series of reactions. 

Ubiquinone (UQ), also known as coenzyme Q, has a benzoquinone structure with a long side chain. The name ubiquinone is for the ubiquitous nature of the quinone. Some bacteria also contain menaquinone (vitamin K2), either in addition to ubiquinone or in place of it. For instance, the reaction center of Rhodopseudomonas viridis contains one ubiquinone and one menaquinone, while in some other bacterial reaction centers both quinones are ubiquinones. Menaquinone has a naphthoquinone structure with a long isoprenoid side chain. The long hydrocarbon side chains in ubiquinone and menaquinone render a high degree of hydrophobicity to these molecules. 

A similar set of absorbance changes were also measured with the PS-I particles that were reconstituted with menaquinone-4 (2-methyl-3-prenyl-1,4-naphthoquinone) and shown in Fig. 12 (A ). The difference between the open- and closed-reaction-center spectra, i.e., [AA(+Q/0)]-[AA(+Q/ )] for the menaquinone-reconstituted particles are shown in Fig. 12 (B ). In the open reaction centers, AA at 695 nm ascribed to P700 was already fully developed at 2 ps delay time. The 685-nm bleaching due to formation of A, had developed by 17 ps but had disappeared 100 ps later, while that at 695 nm remained. The disappearance ofthe 685-nm bleaching is attributable to the reoxidation of Aq and transfer of its electron to the reconstituted menaquinone-4 molecule during the 17-100 ps period. 

Figure 1 Structures of major isoprenoid quinones found in E. coli. (1) Q-8, ubiquinone (2) MK-8, menaquinone (3) DMK-8, demethylmenaquinone. in the structure of MK, the A ring and B ring of the naphthoquinone are shown.

MK biosynthesis by the OSB pathway has been elucidated on the basis of isotopic tracer experiments, isolation of mutants blocked in the various steps, isolation and identification of intermediates accumulated by the mutants, and by enzyme assays. Early isotopic tracer experiments with various bacteria established that methionine and prenyl PPi contribute to the methyl and prenyl substituents of the naphthoquinone. The early isotopic tracer studies and other work have been reviewed by Bentley and Meganathan. " In 1964, Cox and Gibson observed that [G- " C] shikimate was incorporated into both MK and ubiquinone by E. coli, thus providing the first evidence for the involvement of the shikimate pathway." Chemical degradation of the labeled isolated menaquinone (MK-8) showed that essentially all of the radioactivity was retained in the phthalic anhydride. It was concluded that the benzene ring of the naphthoquinone (sic) portion of vitamin K2 arises from shikimate in E. coli The authors further suggested that shikimate was first converted to chorismate before incorporation into MK. A more complete chemical degradation of the MK derived from... 

An easy synthesis of prenyl naphthoquinones, e.g. menaquinone-2 (205 n = 2), was achieved by coupling the appropriate prenyl halide with an organo-copper derivative of the electrochemically derived quinone bisacetal (216). Menaquinone-2 and phylloquinone (204) were also obtained in good yields by reaction of 2-methyl-1,4-naphthoquinone (205 n =0) with geranyl and phytyl halides in the presence of metal dust. A one-step method for the preparation of vitamin K analogues uses cyclodextrin inclusion catalysts.Thus reaction of the diol (217) with allyl bromide in the presence of oxygen and/3-cyclodextrin at pH 9 afforded the menaquinone analogue (218). 

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. 

Rifamycin S derived from [l- C]glycerate showed enhanced n.m.r. signals for C-3 and C-8 which is consistent with incorporation by way of intermediates on the shikimate pathway (Scheme 22). ° Greater enhancement of C-8 by [l- C]glycerate and of C-1 by [l- C]glucose was observed, compared respectively with C-3 and C-10. This indicates that C-1 derives from the methylene carbon of phosphoenol-pyruvate rather than C-4 of tetrose phosphate and that C-8 derives from the carboxy-group of phosphoenolpyruvate. It follows then that C-9 and C-10 of rifamycin S (193) would be the location of the double bond of a dehydroshikimate intermediate. Michael addition to this double bond as in (194) allows completion of the naphthoquinone moiety of rifamycin S in an analogous fashion to the formation of the menaquinones. ... 

Phylloquinones, such as vitamin Ki (37) (Fig. 6.2) are found in all green plant tissues menaquinones and other naphthoquinones are found in bacteria, ngi, and a number of plant families. Naphthoquinones occur free or as glycosides within the plants. They are usually colored and may serve as a source of pigmentation in some plants. 

Phylloquinone (V.K antihemorrhagic V. coagulation V.) is a group of fat-soluble naphthoquinone compounds, with varying sizes of isoprenoid side chain. Mammals can synthesize the side chain but not the naphthoquinone moiety. VK is plentiful in green plants. V.K2 (famoquinone menaquinone-6 2-methyl-l,4-naphthoquinone) is found chiefly in... 

Naphthoquinones with a long isoprenoid side chain are formed in microorganisms (menaquinones, vitamins Kg) and in higher plants (phylloquinone, vitamin K ). Naphthoquinone derivatives with short or absent side chains as well as anthraquinones of the ahzarin type are produced by a few families of higher plants, e.g., Balsaminaceae, Juglandaceae, Rubiaceae. 

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