Vitamin K series

Compounds in the vitamin K series are 2-methyl-l,4-napthoquinones, which are substituted with side chains at carbon 3. FhyUoquinone (Ki type) synthesized in plants and the menaquinones (K2 type) of bacterial origin are the two principal natural classes of vitamin K (Figure 30-6). The principal vitamin Ki (phyUoquinone) bears a saturated, phytol, 20-carbon side chain derived from 4 isoprenoid units this is the main K vitamin produced by plants and is tire major dietary form for humans. K2 shows greater vari-... 

In connection with investigations in the vitamin K series and considering the fact that some quinones and quinone epoxides are of importance in metabolic processes, the preparation of chiral quinone epoxides is of great interest. Such compounds were obtained with an e.e. of 45% by epoxidation of quinones using hydrogen peroxide in an alkaline medium in the presence of quininium benzyl chloride (QBC) [5]. 

Vitamins and K2 exist in nature and are essential to the animal for their effect on the blood-clotting mechanism. While 2-methylnaphthoquinone itself and its related derivatives having isoprenoid side chains in position 3 also promote blood coagulation in varying degrees, coenzyme Q10 shows no activity in the blood-coagulating mechanism. Coenzyme Q10, also called ubiquinone because of its ubiquitous occurrence in animal tissues, is important in its own right, since it plays an essential role in oxidative phosphorylation. As in the case of the vitamin K series, the size of the isoprenoid side chain does not appear to be critical with respect to the oxidative phosphorylation activity of the coenzyme Q series. 

The fact that synthetic, substituted benzoquinones, and also substances of the vitamin K series and ubiquinones are similar in activity to vitamin E or its oxidation products constitutes another indication against the antioxidant hypothesis of vitamin E action. It would hardly be feasible to class all the active compounds as antioxidants. 

Yanotovski et al have discussed the gas chromatography of the vitamin K series and ubiquinones. They showed that the retention times of these vitamins is dependent on the number of isoprene units present. They suggest that it may be possible to identify such compounds using logarithmic plots. 

In the vitamin K series the maximum effect was found in the vitamin K2 analog with 25 C-atoms in the side chain (Table II). The activity of this vitamin Kj form was even somewhat hi er than that of vitamin Ki (Wiss et al., 1959). This may serve as a hint that in addition to vitamin Kscm), Ktoo), Kjcto) (Section II, 3 and 4) this form may also occur in nature. 

Isler, O. and Doebel, K. (1954). Syntheses in the Vitamin K Series. I. The Total Synthesis of Vitamin Ki, Helv. Chim. Acta, 37, pp. 225-233 Isler, O. and Doebel, K. (1954). Synthesis of Vitamin Ki nsing Boron Trifluoride Catalysts, US Patent US 2,683,176 (1956). Novel Naphthalene Componnds and a Process for the Mannfactnre Thereof, British Patent GB 752,420. Puetter, H. andBewert, W. (1981). 2-Methyl-l,4-naphthoqninones, German Patent DE2952709. Eremin, D. and Petrov, L. (2009). Optimization of Conditions for Preparing Vitamin K3 by Oxidation of 2-Methylnaphthalene with Chromium Trioxide in Acid Solutions, Russ. J. Appl. Chem., 82, pp. 866-870. 

This illness is mainly characterized by an age-related bone loss. The detection of osteocalcin in bone was the starting point for a series of studies on the role of vitamin K-dependent proteins in bone development and maintenance and on possible supplemantation therapies. Epidemiologic studies found differences in the risk of hip fractures depending on the dietary vitamin K... 

The fact that pentacarbonyl carbene complexes react with enynes in a chemo-selective and regiospecific way at the alkyne functionality was successfully applied in the total synthesis of vitamins of the Kj and K2 series [58]. Oxidation of the intermediate tricarbonyl(dihydrovitamin K) chromium complexes with silver oxide afforded the desired naphthoquinone-based vitamin K compounds 65. Compared to customary strategies, the benzannulation reaction proved to be superior as it avoids conditions favouring (E)/(Z)-isomerisation within the allylic side chain. The basic representative vitamin K3 (menadione) 66 was synthesised in a straightforward manner from pentacarbonyl carbene complex 1 and propyne (Scheme 38). 

Another important family of quinones, related in structure to those already discussed, are the vitamins K (Fig. 15-24, Box 15-F). These occur naturally as two families. The vitamins K, (phylloquinones) have only one double bond in the side chain and that is in the prenyl unit closest to the ring. This suggests again the possibility of chromanol formation. In the vitamin K2 (menaquinone) series, a double bond is present in each of the prenyl units. A synthetic compound menadione completely lacks the polyprenyl side chain and bears a hydrogen in the corresponding position on the ring. Nevertheless, menadione serves as a synthetic vitamin K, apparently because it can be converted in the body to forms containing polyprenyl side chains. 

Two forms of vitamin K exist in nature. Phylloquinone (vitamin K,) is a specific vitamer synthesized by green plants in the chloroplasts menaquinones (vitamin K2) are a series of structural analogs that are synthesized by bacteria. 

A simple and effective chemical method was developed for quantitatively reducing quinones, based on their reaction with metallic zinc and zinc ions [248]. Comparison of this method with conventional electrochemical reduction [249-252] revealed the chemical method to be considerably superior. A reduction reaction of vitamin Kj and other quinones in the presence of Zn° and Zn2+ eliminates the need to apply large negative potentials and may also be performed in the absence of any applied electrochemical potential. Some quinones used, such as UQ-10, menadione, and vitamin K, of the menaquinone series (MKs 4-10) could all be reduced to their corresponding hydroquinones in these conditions. 

This vitamin occurs in a series of different forms, and these can be divided into two groups. The first is vitamin K, (Figure 9-8), characterized by one double bond in the side chain. The vitamins K2 have a side chain consisting of a number of regular units of the type... 

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 K Uptake and Metabolism. Dietary vitamin and the pharmaceutical form, phytonadione or vitamin K go) must be converted to the K2 series known as menoquinones. The most common of these is menoquinone-4 or K2(20)> This conversion to the K2 series occurs in the liver and possibly the intestinal flora. It involves removing the phytyl chain producing the intermediate menadione. Menadione sometimes is prescribed when there is impaired uptake of lipids from the intestine. There is little storage reserve in the liver, and a deficiency can result when dietary intake of vitamin K is restricted or absorption is impaired. 

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. 

The first part of this account deals with the more recent chemistry of the alkenyl members typified by the Cg, isopentenylphenols, the Ck, dimethyloctadienyl-phenols, the C g, farnesylphenols, and Cjq, phytylphenols. The ubiquinones in the monocyclic and the naphthoquinone vitamins K, and Kj in the bicyclic series are related chemically but are not discussed in this account. 

Injury to the endothelium and exposure of tissue factor on the subendothelial layer to plasma proteins also activate the blood coagulation cascade, which ultimately activates thrombin and Factor XIII Factor XIII cross-links strands of polymerized fibrin monomers to form a stable clot (the secondary hemostatic plug). The blood coagulation cascade consists of a series of enzymes (such as Factor X), which are inactive until proteolytically cleaved by the preceding enzyme in the cascade. Other proteins (Factor V and Factor VIII) serve as binding proteins, which assemble factor complexes at the site of injury. Ca and y-carboxyglutamate residues in the proteins (formed by a vitamin K-dependent process in the liver) attach the factor complexes to phosphoUpids exposed on platelet membranes. Consequently, thrombus formation is rapidly accelerated and localized to the site of injury. 

Isoprenylated Quinones.—A review has been published on the chemistry, distribution, and functioning of vitamins A new volume in the Methods in Enzymology series contains experimental procedures used in the ubiquinone and vitamin K fields. 

Reports on the applications of h.p.l.c. to specific problems include an efficient separation of the reduction products of progesterone, of the conjugates of natural bile acids, and of 2-hydroxy- and 2-methoxy-oestrogens ( catechol oestrogens). Fluorescence detection is reported to be some 500 times more sensitive than u.v. absorption for h.p.l.c. of oestriol. The h.p.l.c. behaviour of compounds in the vitamin D series appears to be correlated with the degree of molecular planarity. " A first report on the use of cholesteric liquid crystals as stationary phases for h.p.l.c. shows promise. Various cholesteryl esters coated on or bonded to Corasil II showed increased capacity factors (k ) when steroids were chromatographed, and permitted some useful separations. 

K2(45), and K2(50), and has developed a method for the rapid identification of vitamin K homologues. (The subscript in parentheses indicates the number of carbon atoms of the side chain in the 3-position of the naphthoquinone ring.) Absorption bands near 1100 and 840cm , which are present in K2 spectra but absent in K, spectra, allow qualitative differentiation to be made between the two homologous series. 

Not only substances of the tocopherol series, but also dimethyl- and trimethylbenzoquinones with isoprenoid side chains, ubiquinones, and members of the vitamin K family were effective in preventing respiratory decline. The activity of these substances, all of them supplemented in the... 

Vitamins of the K series ("Coagulation" vitamins) are chemically classified as prenyl-1,4-naphthoquinones. They are ingested with food originating from all green plants, are involved in oxidative phosphorylation during respiration processes and... 

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