Vitamin hydroquinone

Because of the presence of an extended polyene chain, the chemical and physical properties of the retinoids and carotenoids are dominated by this feature. Vitamin A and related substances are yellow compounds which are unstable in the presence of oxygen and light. This decay can be accelerated by heat and trace metals. Retinol is stable to base but is subject to acid-cataly2ed dehydration in the presence of dilute acids to yield anhydrovitamin A [1224-18-8] (16). Retro-vitamin A [16729-22-9] (17) is obtained by treatment of retinol in the presence of concentrated hydrobromic acid. In the case of retinoic acid and retinal, reisomerization is possible after conversion to appropriate derivatives such as the acid chloride or the hydroquinone adduct. Table 1 Hsts the physical properties of -carotene [7235-40-7] and vitamin A. 

Chromatographic methods including thin-layer, hplc, and gc methods have been developed. In addition to developments ia the types of columns and eluents for hplc appHcations, a significant amount of work has been done ia the kiads of detectioa methods for the vitamin. These detectioa methods iaclude direct detectioa by uv, fluoresceace after post-column reduction of the quiaone to the hydroquinone, and electrochemical detection. Quantitative gc methods have been developed for the vitamin but have found limited appHcations. However, gc methods coupled with highly sensitive detection methods such as gc/ms do represent a powerful analytical tool (20). 

The epoxide of vitamin K is involved in the regeneration of the anticoagulant vitamin (a naphthoquinone) from the active hydroquinone form (81JA5939). 

Encouraged by the short synthesis of K vitamins, the chromium-mediated benzannulation was extended to the synthesis of vitamin E 68 [59]. The problem of imperfect regioselectivity of alkyne incorporation - which did not hamper the approach to vitamin K due to the final oxidation to the quinone - was tackled by demethylation of both regioisomeric hydroquinone monomethyl ethers 67 to give the unprotected hydroquinone. Subsequent ring closure yielded a-tocopherol (vitamin E) 68 (Scheme 39). 

Vitamin K is the cofactor for the carboxylation of glutamate residues in the post-synthetic modification of proteins to form the unusual amino acid y-carboxygluta-mate (Gla), which chelates the calcium ion. Initially, vitamin K hydroquinone is oxidized to the epoxide (Figure 45-8), which activates a glutamate residue in the protein substrate to a carbanion, that reacts non-enzymically with carbon dioxide to form y-carboxyglut-amate. Vitamin K epoxide is reduced to the quinone by a warfarin-sensitive reductase, and the quinone is reduced to the active hydroquinone by either the same warfarin-sensitive reductase or a warfarin-insensitive... 

Similarly, 2,3,5-trimethyl-1,4-hydroquinone (TMHQ), a key intermediate in the synthesis of vitamin E, is produced via oxidation of 2,3,6-trimethylphenol to the corresponding benzoquinone. Originally this was performed by reaction with chlorine followed by hydrolysis, but this process has now been superseded by oxidation with O2 in the presence of a Cu2Cl2/LiCl catalyst (see Fig. 2.20) (Mercier and Chabardes, 1994). Alternatively, this oxidation can also be cataly.sed by a heteropolyanion (Kozhevnikov, 1995). 

A number of useful reviews have appeared in the course of the last few years, and a number of chemicals, such as vitamin C, p-tetralone, hexafluoropropylene oxide, piperidine, glyoxalic acid, pinacol, p-hydroxypropiophenone, sebacic acid, p-anisaldehyde, maltol/ethyl maltol. Rose oxide, linalool, perfluorooctanoic acid, hydroquinone, etc., that are commercially made (or can be made) electrochemically have been catalogued. 

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 role of ubiquinone (coenzyme Q, 4) in transferring reducing equivalents in the respiratory chain is discussed on p. 140. During reduction, the quinone is converted into the hydroquinone (ubiquinol). The isoprenoid side chain of ubiquinone can have various lengths. It holds the molecule in the membrane, where it is freely mobile. Similar coenzymes are also found in photosynthesis (plastoquinone see p. 132). Vitamins E and K (see p. 52) also belong to the quinone/hydroquinone systems. 

Fig. 5. Examples of GC-MS data for vitamin E in a vegetable oil and cattle feedlot soil (a) vegetable oil, sum of key ions mjz 129 (TMS for sterols), 474, 488 and 502 of tocopherols as TMS), (b) feedlot soil, sum of key ions ra/z 416 and 430 for tocopherols, a-tocopheryl acetate, and the metabolite (as free phenols), and (c) mass spectrum of a-tocopherol hydroquinone (V).

I. 1.4.1] catalyzes the reaction of 2-methyl-3-phytyl-l,4-naphthoquinone with oxidized dithiothreitol and water to produce 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-l,4-naphthoquinone and 1,4-dithiothreitol. In the reverse reaction, vitamin K 2,3-epoxide is reduced to vitamin K and possibly to vitamin K hydroquinone by 1,4-dithioer-ythritol (which is oxidized to the disulfide). Some other dithiols and butane-4-thiol can also act as substrates. This enzyme is strongly inhibited by warfarin. 

In normal individuals phytonadione and the menaquinones have no activity while in vitamin K deficiency the vitamin promotes the hepatic biosynthesis of factor II (prothrombin), factor VII, factor IX and factor X. Vitamin K functions as an essential cofactor for the enzymatic activation of precursors of these vitamin K dependent clotting factors. The quinone structure of the active form of vitamin K, i.e. reduced vitamin K or hydroquinone. 

Vitamin cycle—metabolic interconversions of vitamin associated with the synthesis of vitamin -dependent clotting factors. Vitamin K1 or K2 is activated by reduction to the hydroquinone form (KH2). Stepwise oxidation to vitamin epoxide ( ) is coupled... 

A closely related and important family of chro-manols are the tocopherols or vitamins E (Fig. 15-24, Box 15-G). Tocopherols are plant products found primarily in plant oils and are essential to proper nutrition of humans and other animals. a-Tocopherol is the most abundant form of the vitamin E family smaller amounts of the P, 8, and y forms occur, as do a series of tocotrienols which contain unsaturated isoprenoid units.495 The configuration of a-tocopherol is 2R,4 R,8 R as indicated in Fig. 15-24. When a-toco-pherol is oxidized, e.g., with ferric chloride, the ring can be opened by hydrolysis to give tocopherolquinones (Fig. 15-24), which can in turn be reduced to tocopherol-hydroquinones. Large amounts of the tocopherolquinones have been found in chloroplasts. 

All are probably bound to the microsomal membranes.503 507a An NADPH-dependent reductase reduces vitamin K quinone to its hydroquinone form. Conversion of Glu residues to Gla residues requires this reduced vitamin K as well as 02 and C02. During the carboxy-lation reaction the reduced vitamin K is converted into vitamin K 2,3-epoxide (Eq. 15-55).508 The mechanism is uncertain but a peroxide intermediate such as that shown in Eq. 15-56 is probably involved. This could be used to generate a hydroxide ion adjacent to the pro-S -H of the glutamate side chain of the substrate. This hydrogen could be abstracted by the OH to form... 

An assay for the determination of vitamin K3 (2-methyl-1,4-naphthoquinone) by a combination of both constant-potential and constant-current cou-lometry has been reported [13]. The assay requires the two-electron reduction of the compound to the corresponding hydroquinone at a mercury pool electrode (E = -0.60 V vs. SCE) in acetate buffer, pH 5.9, followed by the coulometric titration of the reduction product with electrogenerated Ce(VI). This method is preferable to the standard method requiring preliminary reduction to the hydroquinone by zinc dust in acid medium, followed by titration with standard Ce(IV) solution. It is capable of low-level determination (1-2 mg) of this vitamin in pharmaceuticals, biological fluids, and foods. 

The first combined HPLC-electrochemical measurements of vitamin K used the reductive mode, but this technique suffered from interference from the reduction of oxygen. A redox method was later developed that eliminated this interference, and provided a 10-fold increase in sensitivity over photometric detection and an improved selectivity. The coulometric detector employed in the redox mode is equipped with a dual-electrode cell in which phylloquinone is first reduced upstream at the generator electrode and the hydroquinone is reoxidized downstream at the detector electrode. 

Fig. 14. Schematic representation of light-driven (2e + 2H+) symport across a membrane via the quinone carrier molecule vitamin Kj and its hydroquinone form proflavine (PF)-sen-sitized photoreduction of methyl-viologen MV2+ in the RED phase, yields the reducing species MV+, with simultaneous oxidative decomposition of EDTA used as electron donor the OX phase contains ferricyanide as electron acceptor [6.49].

The oxidation of vitamin K hydroquinone monoanion (17) with labelled, 802 in THF leads to vitamin K oxide (18) in which the epoxide oxygen is fully labelled, hi addition, partial incorporation of 180 at the carbonyl oxygen is observed (on the basis of the mass spectrum).215 This is most readily explained by invoking a dioxetane intermediate (19) as opposed to the alternative intermediacy of a 2-hydroperoxide (20), where only the epoxide oxygen would be expected to be labelled. 

Vitamin K cycle—metabolic interconversions of vitamin K associated with the synthesis of vitamin K-dependent clotting factors. Vitamin K1 or K2 is activated by reduction to the hydroquinone form (KH2). Stepwise oxidation to vitamin K epoxide (KO) is coupled to prothrombin carboxylation by the enzyme carboxylase. The reactivation of vitamin K epoxide is the warfarin-sensitive step (warfarin). The R on the vitamin K molecule represents a 20-carbon phytyl side chain in vitamin Ki and a 30- to 65-carbon polyprenyl side chain in vitamin K2. 

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