Phytyl side chain

Figure 16.10 Biosynthesis of phylloquinone (vitamin K-j) from 1,4-dihydroxynaphthoic acid. The key step that joins the 20-carbon phytyl side chain to the aromatic ring is a Friedel-Crafts-like electrophilic substitution reaction.

A different set of photoaffinity probes (29, Fig. 12) was designed and synthesized by Atkinson et al. The photosensitive 4-azido-2,3,5,6-tetrafluorobenzyloxy group was placed at the terminus of the phytyl side chain [112]. 

Figure 10.15 The chlorophyll a and b molecules have vinyl, ethyl and phytyl side chains as R, R3 and R4, respectively chlorophyll a has a methyl group as R2, which is replaced by a formyl group in chlorophyll b. (From Voet and Voet, 2004. Reproduced with permission from John Wiley Sons., Inc.)...

Phytene is an example of a diterpene. It is found as the phytyl side chain in chlorophyll a and vitamin K. Haslene is an example of a sesterpene. It is an imsaturated and branched simple lipid synthesized by marine pennate diatoms. One of the largest femilies of terpenes... 

Vitamin Kj (8.60) is a phytyl-naphthoquinone occurring in the green leaves of most plants. The several related active compounds differ in the length of the phytyl side chain. 

Further work on the structural requirements for the antioxidant effect has been performed with micelles and liposomes [ 104]. This group concluded that the antioxidant properties of vitamin E and its model compound without the phytyl side-chain were similar within micelles, liposomes and homogeneous solution but that the phytyl side-chain enhances the retention of vitamin E in liposomes and suppresses the transfer of the vitamin between liposomal membranes. 

This effect was seen only in hypoxia, not normoxia, was dose-dependent within the range 0.2-200 /rM, and provided a simple in vitro model for investigating the mode of action of the vitamin. By examining the structure-activity relationship of the response, compounds with a phytyl side-chain, phytol and vitamin K-l (phytomenadione), of similar length to vitamin E (9) were found to be also active, but compounds that had structures which resembled the chroman ring of the vitamin, vitamin K-3 (menaphthone) and Trolox, were antagonists of the responses to the phytol side-chain effects. 

In heart tissue, phytol also had an effect similar to that of vitamin E, while Trolox did not (Table 5.4) [223], suggesting that the phytyl side-chain was... 

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. 

Fig. 1 Schematic representation of the spatial arrangement of the chromophores involved in the first steps of photosynthetic charge-separation in rhodopseudomonas viridis. Orientation of phytyl side-chains is indicated by wavy lines, furthermore the position of an additional bacteriochlorophyll unit is sketched.

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... 

Vitamin K2 (menaquinone) represents a series of compounds in which the phytyl side chain of phytonadione has been replaced by a side chain built up of 1-14 isoprenyl units. It has been reported that vitamin K2 with four isoprenyl units (4) induced the monocytic differentiation of human myeloid leukemia cell lines [58], or apoptosis in isolated osteoclast [59] and human ovary cancer cells [60]. We have recently found that vitamin K2 derivatives (1-3) induced some tumor-specific cytotoxicity and non-apoptotic cell death in oral carcinoma [61]. As an extension of the search for tumor-specific substances targeted against human oral squamous, hepatocellular carcinoma, and promyelocytic leukemia cell lines, we investigated the QSAR of seven vitamin K2 derivatives (1-7) (Fig. 18), by conventional and recent techniques of computation chemistry, such as the concept of absolute hardness [ 16-18]. 

E)- and (Z)-4-Benzyloxy-3-hydroxy-l-(4-methylphenyl)-l-butene gave, with triethyl orthoacetate in the presence of pivalic acid, the same, but enantiomeric, (R,E) and (.S , )-6-benzyloxy-3-(4-methylphenyl)-4-hexenoate [5 65%, 87% ee from the (E -butene R 78%, 90% ee from the (Z)-butene] (see p 3374)288. Similarly, (R,E)- and (S, )-6-benzyloxy-3-(4-methylphenyl)-4-hexenal are obtained by heating the (E)- and (Z)-butenes with excess methyl vinyl ether in the presence of mercury(II) acetate in a sealed tube [S 72 %, 90 % ee from the (E)-butene R 71 %, 85% ee from the (Z)-butcnc]288. Analogous strategies have been used to construct the phytyl side chain of tocopherol (see p 3370)289,290. 

In green plants, K plays a role in photosynthesis and is present in photosystem I. K has been identified as the secondary acceptor Aj in photosystem It should be pointed out that the structure of K is identical to that of MK except that the prenyl side chain is replaced by a phytyl side chain. Hence, it is assumed that the biosynthetic pathway in plants is identical to that in bacteria. 

Two bacteriochlorophyll monomers, and Bg, are located next to the primary donor D, but they are buried deeper in the membrane. Their positions are fixed by helices B, C, D, and de of the L- and M-subunits, respectively. How these so-called accessory bacteriochlorphylls are involved in the ET has been the subject of a long debate (Holzapfel et al., 1990 Kirmaier and Holten, 1991). Some evidence for their function as true electron carriers has been provided by subpicosecond absorption spectroscopy (Arlt et al., 1993 Zinth et al., 1996). The Bg molecule facilitates the triplet energy transfer between D and the carotenoid (Frank and Violette, 1989). B and Bg follow the local Cj symmetry. Their tetrapyrrole rings are superimposed by a rotation (M on L) of -175.8 (Deisenhofer and Michel, 1989a,b) which is not as perfect as for the D /Dgpair. As in the case of Dg,the phytyl side chain of Bg interacts with the M-subunit... 

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. 

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