Vitamin quinone derivative

The vitamin E derivative a-tocopherolquinone (Fig. 15-24) can also serve as an electron carrier, being reversibly reduced to the hydro-quinone form a-tocopherolquinol. Such a function has been proposed for the anaerobic rumen bacterium Butyrovibrio fibrisolvens 497... 

Vitamin K, which plays a role in the coagulation of blood, is a naphtho-1,4-quinone derivative. Co-enzymes Q, the ubiquinones, which are present in the cells of organisms, are involved in the transportation of electrons, for example in the oxidation of NADH to NAD. Commercially important quinones include the anthraquinone dyes (see Chapter 12) and the dyes which produce the colours in conventional photography. 

Even more convenient are the conditions for determining quinones[14] at platinum or carbon solid electrodes because their reversible 2-electron (or 2 one electron steps in aprotic media) reduction proceeds at considerably positive potentials. This property could be utilized in constructing an electrochemical detector for vitamin K derivatives ... 

The decreasing importance of GC as an analytical technique for vitamin E becomes evident from the number of systems/applications inventoried in the first and second editions of this book. In the 1985 edition, 64 systems, 61 of which used packed columns, were listed. However, the number of papers that appeared between 1985 and 1989, included in the second edition was only five. A milestone in the history of GC of vitamin E was the first and, to the best of our knowledge so far only separation, in 1967, of p- and y-tocopherols as their quinone derivatives on a packed column, using a special binary liquid phase. The separation of TMS ethers of both isomers was achieved in 1975 on a 32-m open tubular column coated with a polar PZ-176 liquid phase and, later on a 30-m DB-5 capillary column. All tocopherols and tocotrienols were successfully resolved in as little as 15 min by capillary GC on a 20 m OV-17 column. GC was also the first method to distinguish (partially) between stereoisomers (see VIA). 

The recommended daily allowance for vitamin E ranges from 10 international units (1 lU = 1 mg all-rac-prevent vitamin E deficiency in humans. High levels enhance immune responses in both animals and humans. Requirements for animals vary from 3 USP units /kg diet for hamsters to 70 lU /kg diet for cats (13). The complete metaboHsm of vitamin E in animals or humans is not known. The primary excreted breakdown products of a-tocopherol in the body are gluconurides of tocopheronic acid (27) (Eig. 6). These are derived from the primary metaboUte a-tocopheryl quinone (9) (see Eig. 2) (44,45). 

In the case of ubiquinones we have already considered the ability of quinones to react with superoxide and other free radicals. Naphthoquinones, vitamin K and its derivatives, especially menadione, are the well known producers of superoxide through redox cycling with dioxygen. However, in 1985, Canfield et al. [254] have shown that vitamin K quinone reduced the oxidation of linoleic acid while vitamin K hydroquinone stimulated lipid peroxidation. Surprisingly, later on, conflicting results were reported by Vervoort et al. [255] who found that only hydroquinones of vitamin K and its analogs inhibited microsomal lipid peroxidation. 

In order to model the oxygenation of vitamin K in its hydroquinone form, a naph-thohydroquinone derivative with a 1-hydroxy group and 4-ethyl ether was prepared and its alkoxide subjected to oxidation with molecular oxygen. Products consistent with two possible mechanisms were isolated, the epoxy-quinone which must derive from a peroxy anion intermediate at the 4-position, and a 2-hydroxy product which... 

The principal role of vitamin K is in the post-translational modification of various blood clotting factors, in which it serves as a coenzyme in the carboxylation of certain glutamic acid residues present in these pro teins. Vitamin K exists in several forms, for example, in plants as phyllo quinone (or vitamin K-i), and in intestinal bacterial flora as Inenaquinone (or vitamin K2). For therapy, a synthetic derivative of vita rrri K, menadione, is available. 

A new synthetic route to alkyl-substituted quinones has relied on the photochemical reaction of 2,3-dichloro-l,4-naphthoquinone with a thiophene derivative (77CL851). Irradiation of a benzene solution of the quinone and thiophene by a high pressure mercury lamp gave photoadduct (295) in 56% yield. Desulfurization of this compound over Raney nickel (W-7) gave the 2-butyl-1,4-naphthoquinone derivative (296 Scheme 62). Alkyl-substituted quinones such as coenzyme Q and vitamin K, compounds of important biological activity, could possibly be prepared through such methodology. 

Derivatives of ubiquinones are antioxidants for foodstuffs and vitamins (qv) (217,218). Ubichromenol phosphates show antiinflammatory activity (219). Chromanol compounds inhibit oxidation of fats and can be used in treatment of macrocytic anemias (220). Monosulfate salts of 2,3-dimethoxy-5-methyl-6-substitutedhydroquinone have been reported to be inhibitors of lipid oxidation in rats (221). Polymers based on chloranilic and bromanilic acid have been prepared and contain oxygenated quinones (63), which are derived from 1,2,3,4-benzenetetrol (222). 

Use of transition metal catalysts opens up previously unavailable mechanistic pathways. With hydrogen peroxide and catalytic amounts of methyl trioxorhe-nium (MTO), 2-methylnaphthalene can be converted to 2-methylnaphtha-l,4-qui-none (vitamin K3 or menadione) in 58 % yield and 86 % selectivity at 81 % conversion (Eq. 10) [43, 44]. Metalloporphyrin-catalyzed oxidation of 2-methylnaphtha-lene with KHSOs can also be used to prepare vitamin K3 [45]. The MTO-catalyzed process can also be applied to the synthesis of quinones from phenols [46, 47]. In particular, several benzoquinones of cardanol derivatives were prepared in this manner [48], The oxidation is thought to proceed through the formation of arene oxide intermediates [47]. 

Tomboulian et al. (2002) has reported that butylated hydroxytoluene (BHT) can impart a "burnt plastic" odor and is an additive in HDPE pipes. Quinone may be derived from BHT due to interactions with residual chlorine in pipes (Anselme et al., 1985). Yam et al. (1996) reported that antioxidants, such as vitamin E, Irganox 1010, and BHT, contributed to off-flavors in water. Vitamin E yielded less off-flavor, possibly due to lower aldehyde and ketone concentrations. Extrusion temperatures over 280 °C and exposure time for melt contributed to more oxidation of LDPE films and higher intensities of off-flavors in water in contact with LDPE with different antioxidants (Andersson et al., 2005). 

The fat-soluble vitamins include vitamin A (retinol), a colorless compound resulting from cleavage of /3-carotene, vitamin D3 (cholecalciferol) a steroid, and vitamins E and K (tocopherols and menadione and their derivatives, respectively), which consist of isoprene and phenolic-quinone components. 

Oligomerization of isoprenoids under elimination of pyrophosphate affords the precursors for the biosynthesis of monoterpenes, sesquiterpenes, diterpenes, triterpenes, and tetra-terpenes (93). Long-chain oligomer pyrophosphates also supply the side chains of vitamin E (99, a-tocopherol. Fig. 11), heme a (18), chlorophyll (17, Fig. 2), and the quinone type cofactors, including vitamin K (menaquinone, 98) and coenzyme QIO (ubiquinone, 97). The quinone moieties are derived from hydroxybenzoate that is synthesized from tyrosine in animals or from chorismate in microorganisms (53, 54). 

Quinones and, in particular, naphthoquinone derivatives are industrially valuable products for further processing and for direct use due to their pronounced bioactivity [la,b], 2-Methyl-1,4-naphthoquinone, vitamin K3 ( menadione ), is the basis of the vitamin K group (coagulation vitamins). The skeleton of 2-methyl-1,4-naphthoquinone is common to all fat-soluble K vitamins. Derivatives of vitamin K promote the formation of prothrombin and other blood coagulation factors. They are used on an industrial scale as supplement in animal feed, but are also employed in the treatment of Melaena neonatorum in newborn babies. Trimethyl-p-benzoquinone is a key compound for the synthesis of vitamin E, active as antioxidant agent. As an example, the current method of the production of trimethyl-p-benzoquinone on an industrial scale is p-sulfo-nation of 2,3,6-trimethylphenol followed by stoichiometric oxidation using Mn02 [Ic]. 

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). 

The photoenolization of the quinone (286) can be carried by irradiation at 313 or 365 nm in acid solution. The steady state irradiation has identified the product as the unstable hydroxylated compound (287) which is formed via the enol (288). The presence of this intermediate was detected in a laser flash study of the reaction. The quinones (289) undergo cyclization when irradiated with visible light.The mechanism by which the compounds (289) are transformed into the derivatives (290) involves the production of an excited state that is either a zwitterion or a biradical. After the transfer of a hydrogen the intermediate (291) is formed. It is within this species that cyclization occurs to give the final products. (2+2)-Cyclo-adducts such as (292) and oxetanes can be obtained by the photochemical addition of quinones to homobenzvalene. Interest in the photo-SET in quinone systems has led to the synthesis of the pyropheophytin substituted naphthoquinone dyads (293). A pulse radiolysis study of vitamin K in solution has been reported. 

Chemistry. A new method has been described for the regio- and stereo-controlled polyprenylation of quinones by means of trimethyltin derivatives. The polyprenyl trimethylstannanes (200) were prepared from the polyprenyl halides (201) and trimethylstannyl-lithium, and were then coupled with the required benzo-quinone (202) or naphthoquinone (203) in the presence of BFs-ether to give a quinol which was reduced with Ag20 to the ubiquinone (204) or vitamin K... 

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