Vitamin K compounds

Vitamin K compounds ate yellow solids or viscous liquids. The natural form of vitamin is a single diastereoisomer with 2 (E), 7 (R), ll (R) stereochemistry. The predominant commercial form of vitamin is the racemate and a 2 (E)j (Z) mixture. Table 1 fists some physical and spectral properties of 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). 

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. 

A better understanding of the mechanism of action of anti-vitamin K compounds has been gained. They lower blood levels of an active prothrombin molecule by prevention of (j)(j)3 uptake on the glutamic acid residues in the molecule that allows Ca binding.78 These compounds are discussed in a review by O Reilly.73 No new compounds of this type are reported. ... 

A new method has been devised for the spectrophotometric determination of vitamin K compounds as their Ti complexes.H.p.l.c. procedures for determination of vitamin and ubiquinone homologues and isomers have been reported. 

Two compositions of the liposoluble vitamin K compound phytomenadione are listed in Table 37.7. In (4) a nonionic surfactant is used, in (5) lecithin-bile acid mixed micelles are the solubilizing principle. 

Novobiocin does not belong to any particular chemically defined group of antibiotics although there are a number of groupings in e molecule which may be related to specific effects. The antibiotic is a coumarin derivative (I) (see p. 40) and has been shown to inhibit oxidative phosphorylation in Mycobacterium phlei [82]. A vitamin K compound is necessary for electron transport in this organism, and both novobiocin-induced inhibition of electron transport and inhibition of growth are reversed by vitamin K. 

These are the synthetic derivatives of vitamin K. Jirasek and Schwank (1965) reported a case of contact dermatitis to vitamins K3(menadione) and K4 (men-adiol). Romaguera et al. (1980) and Camarasa and Barnadas (1982) demonstrated that patients allergic to vitamin K3 sodium bisulfite practically always react to vitamin K4 as well. No cross-sensitivity, however, seems to occur with the natural vitamin K compound (Jirasek and Schwank 1965). The induction time varied from 3 weeks to 4 months in all cases. 

Haroon et al. (38) developed a dual electrode system for the detection of vitamin K compounds. The device utilized two sequential generator/detector electrodes. Vitamin K was electrolyzed at the first electrode and the reaction products were then detected electrochemically at a second electrode. The minimum mass of vitamin that they claim could be detected was 100 pg. They applied their system to the analysis of rat liver extracts and claimed it was superior in both sensitivity and specificity to the UV detector. 

Martius (1958) isolated from the tissue of rats fed with C Mabeled menadione a labeled K compound which proved to be similar to both vitamin Ki and K. Comparison with synthetic specimens indicated a vitamin K compound with an unsaturated C20 side chain. Martius discovery of vitamin Kjcio) in the tissue of mammals fed with menadione is of the utmost importance and will be further discussed in subsequent sections. 

Fia. 6. Paper chromatography of vitamin K compounds. Method Green and Dam (1954). Paper Whatman No. 1 impregnated with Dow Corning Silicone No. 1107. Solvent system isopropanol acetic acidrwater (600 25 375). Time 14 hours. Detection ultraviolet light. 

Vitamin Ki is best synthesized by condensation of a menadiol 1-ester with phytol or isophytol and subsequent saponification and oxidation. Vitamin Ki synthesized from phytol appears to be identical with the natural product vitamin Ki from synthetic isophytol differs slightly in having a racemic phytyl chain. The double bonds in /3,7-position of all vitamin K compounds have the same, most probably the irons, configuration. 

The observation that menadione is transformed into a vitamin K2(2o> in the animal is in agreement with the assumption that only vitamin K compounds with polyisoprene-like side chains are metabolically active. From investigations on the participation of mevalonic acid in the biosynthesis of the ubiquinones, (the side chains having the same structural arrangement as in vitamin K2) evidence is given that this precursor is also used for the... 

Little is known about the reactions of vitamin Ki in foods. The vitamin K compounds are destroyed by light and alkali. They are relatively stable to atmospheric oxygen and exposure to heat. 

After hydrolysis of triglycerides, denaturation (ethanol) and extraction (hexane) of milk samples are similar to those procedures used in preparation of plasma samples. EHie to high concentrations of coextracted lipophilic compounds, a semipreparative HPLC cleanup step often is used in these preparations. Indyk et al. (92) and Lambert et al. (99) used adsorption HPLC and hexane/isopropanol mixtures for cleanup and a reversed-phase HPLC for detection, whereas Isshiki et al. (94) used a Cig reversed-phase system with a methanol/acetonitrile mixture for cleanup and a C2 or C3 reversed phase for detection. Canfield et al. (95,96) worked with two open-column chromatography systems (silica) to isolate vitamin K compounds prior to HPLC detection, whereas Schneiderman et al. (98) introduced a completely different method for isolation of these compounds. They used supercritical fluid extraction (SFE) with CO2 as solvent to determine VKl in powdered infant formulas. Details of this particular method will be discussed later in this chapter. 

Following isolation and various cleanup procedures, final detection and quantitation of vitamin K compounds can be performed in numerous ways with respect... 

Y Haroon, DS Bacon, JA Sadowski. Reduction of quinones with zinc metal in the presence of zinc ions application of post-column reactor for the fluorimetric detection of vitamin K compounds. Biomed Chromatogr 2(l) 4-8, 1987. 

KW Davidson, JA Sadowski. Determination of vitamin K compounds in plasma or serum by high-performance liquid chromatography using postcolumn chemical reduction and fluorimetric detection. Vitam Coenzymes PT L 282 408-421, 1997. 

Absorption. Since the natural vitamins K (K, and K,) are fat soluble, they require bile and pancreatic juice in the intestine for maximum absorption. Thus, anything that interferes with the normal absorption of fat, interferes with the absorption of natural vitamin Ks. By contrast, some of the synthetic vitamin K compounds are water soluble and more easily absorbed. Absorption takes place mainly in the upper part of the small intestine. Normally, 10 to 70% of the vitamin K in the intestines is absorbed. However, there is uncertainty as to how much of the vitamin Kj that is synthesized in the colon is absorbed, based on the fact that absorption of nutrients in general from the large intestine appears to be limited because of the nature of the epithelial lining. 

The synthesis of vitamin K compounds 158 Synthesis ofdiphenylmethane and its derivatives 163 One-pot synthesis of( )-menthol and its intermediates 165... 

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