L,4-dihydroxy-2-naphthoic acid

Animals caimot synthesize the naphthoquinone ring of vitamin K, but necessary quantities are obtained by ingestion and from manufacture by intestinal flora. In plants and bacteria, the desired naphthoquinone ring is synthesized from 2-oxoglutaric acid (12) and shikimic acid (13) (71,72). Chorismic acid (14) reacts with a putative succinic semialdehyde TPP anion to form o-succinyl benzoic acid (73,74). In a second step, ortho-succmY benzoic acid is converted to the key intermediate, l,4-dihydroxy-2-naphthoic acid. Prenylation with phytyl pyrophosphate is followed by decarboxylation and methylation to complete the biosynthesis (75). 

Menaquinone. The incorporation of [2- C]mevalonate and [2- C]-2-methyl-l,4-naphthoquinone into MK-4, normally considered a bacterial quinone, has been demonstrated in marine invertebrates such as crabs and starfish." Incorporation into 2,3-epoxy-MK-4 (163) was also observed. Cell-free extracts have been prepared from Escherichia coli which catalyse the conversion of o-succinylbenzoic acid (164) into l,4-dihydroxy-2-naphthoic acid (165) and menaquinones. In the presence of farnesyl pyrophosphate the major menaquinone produced was MK-3. Genetic studies with mutants of E. coli K12 that require (164) offer support for the generally accepted pathway for MK biosynthesis via (164) and (165)." The enzyme system that catalyses the attachment of the polyprenyl side-chain to 1,4-dihydroxy-2-naphthoic acid to form demethylmenaquinone-9 (166) has been isolated from E. colU ... 

Beginning with l,4-dihydroxy-2-naphthoic acid the preparation of the Step 1 reagent is described by the author. 

Biosynthesis. The asymmetric incorporation of 4-(2 -carboxyphenyl-4-oxobu-tyrate [o-succinylbenzoate (211)] into phylloquinone by Zea mays has been reported. The incorporation of (211), via its coenzyme A thioester, into l,4-dihydroxy-2-naphthoic acid (212) and menaquinone has been studied in cell-free extracts of Mycobacterium phlei and Micrococcus luteus. The biosynthesis and metabolism of menaquinone-4 in the crab has been described. A soluble enzyme complex capable of converting 2-octaprenylphenol (213) into... 

Formation of the coenzyme A ester of the aliphatic carboxyl group of o-succinylbenzoic acid (38) appears to activate the methylene proton sufficiently to permit attack at the aromatic carboxyl group (Fig. 6.7). 2-Carboxy-4-oxotetra-lone (COT) (43) and/or l,4-dihydroxy-2-naphthoic acid (DHNA) (40) are likely intermediates for later stages of synthesis. The enzymatic conversion to DHNA with naphthoate synthase (which consists of OSB CoA synthetase and DHNA synthetase) requires ATP, Mg ", and coenzyme A. 1,4-Dihy-droxy-2-naphthoic acid (40) is a precursor of vitamin K2 (35) and menaquinones (such as 44) (Inouye and Leistner,... 

Juglone (7) (from Jug Ians regia) and lawsone (41) (from Impatiens balsamina) both come from shikimic acid (Fig. 6.8) (Packter, 1980). The initial steps of biosynthesis are identical to those of vitamin K2 (Inouye and Leistner, 1988 Kolkmann and Leistner, 1987). Either l,4-dihydroxy-2-naphthoic acid (40) or 2-carboxy-4-oxotetralone (COT) (43) is incorporated efficiently into both juglone and lawsone (Leistner, 1981). Biosynthesis of juglone proceeds through a symmetrical intermediate 1,4-naphthoquinone (42) is an efficient precursor (Leistner, 1981). In contrast, the biosynthesis of lawsone (41) does not appear to involve a symmetrical intermediate (Haslam, 1974 Inouye and Leistner, 1988). 

Phylloquinone (37), plastoquinone, ct-tocopherol, and ubiquinone (13) (Fig. 6.2) are produced by a cell suspension culture from Morinda lucida (Rubiaceae). Changes in environmental, hormonal, and other cultural conditions result in accumulation of anthraquinones in cultures of Galium, Morinda, diXidRubia (all Rubiaceae). The addition of o-succi-nylbenzoic acid (38) causes an increase in the amount of anthraquinones produced. 2-Carboxy-4-oxotetralone (43) or l,4-dihydroxy-2-naphthoic acid (40) appear to be intermediates in the synthesis of both anthraquinones and phylloqui-nones. 

Intact plants and cell cultures of Streptocarpus dunnii (Gesneriaceae) contain several 1,2-naphthoquinones with a reversed prenyl side chain, such as that in dunnione (66) (Fig. 6.16), l-Hydroxy-2-methylanthraquinone (67) and 1-hydroxy-2-(hydroxymethyl)anthraquinone (68) were also isolated from this culture. Administration of [1-carboxy- C]<9-succinylbenzoate revealed that was incorporated into the 1-position of dunnione and the 10-position of anthraquinones. These results, together with those of feeding experiments in which lawsone (41) and its 2-prenyl ether (69) were applied, suggested that dunnione (66) was formed by a Claisen-type rearrangement at the 2-position of 2-carboxy-4-oxotetralone (COT) (43), whereas anthraquinones were formed by prenylation at the 2-position of 2-carboxy-4-oxo-tetralone (COT) (43) or l,4-dihydroxy-2-naphthoic acid (40) (Inouye and Leistner, 1988). 

Biosynthesis of naphthoquinones lawsone and juglone starts, similarly to phylloquinone biosynthesis, from the shikimic acid metabolite chorismic acid, and proceeds via the intermediate l,4-dihydroxy-2-naphthoic acid. The precursor of alkannin is 4-hydroxybenzoic acid, which is another metabolite of... 

Additives for High Performance Applications 1.1.7 l,4-Dihydroxy-2-Naphthoic Acid... 

A l,4-dihydroxy-2-naphthoic acid standard solution of 5 pgmV was analyzed five times in a row by either the original or the improved method. The relative standard deviation of the peak area was 37.0% and 1.6%, respectively. The linearity of the improved method was confirmed in the range of 0.25-10 pgml. These data indicate that the addition of DL-dithiothreitol to the mobile phase improves the precision of the analysis of l,4-dihydroxy-2-naphthoic acid by HPLC (66). 

Biosynthesis of Lawsone. -The biosynthesis of this naphthaquinone has been investigated for intermediary symmetry by Grotzinger and Campbell. The naphthalene nucleus of lawsone (54) i derived from shikimate with three non-carboxyl carbon atoms of glutamate, and a symmetrical 1,4-naphthaquin-one or the acid (55) are both possible intermediates. Feeding experiments in Impatiens balsamina now establish that [2- C] acetate predominantly labels C-2 of (54), so that the unsymmetrical intermediate (55) must be involved (see Scheme 9). An alternative route from (54) to (55) from that illustrated is via l,4-dihydroxy-2-naphthoic acid, but this could not be detected as an intermediate, nor was it incorporated when fed to the plants. 

A series of nonpolar matrices were evaluated for the analysis of synthetic polymers and compared to that of conventional ones. Among substituted polycyclic aromatic hydrocarbons l,4-dihydroxy-2-naphthoic acid, 9-anthracenecarboxylic acid (9-ACA), and its mixtures with 5-methoxysalicylic acid ( super 9-ACA) provided better signal for analysis of synthetic polymers - poly(ethylene glycol), poly(propylene glycol), Jeffamine,... 

When [l-carboxy- C]o-succinyl benzoate is administered to plants of Catalpa ovata (Bignoniaceae), it is incorporated into a-lapachones (such as 45), catalponol (46), and catalpalactone (47). Examination of the ratio in catalponol (46) after administration of [l-carboxy- C,2 - H2]o-succinylbenzoate reveals that the two protons at the 2 -posi-tion are both retained in the 3-position of catalponol (Fig. 6.9). Thus, prenylation occurs at the 2-position and does not involve an aromatic compound such as 1,4-dihydroxy-2-naphthoic acid (DHNA) (40) (Inouye and Leistner, 1988). 2-Carboxy-4-oxotetralone (COT) (43) or 2-carboxy-4-hy-droxy-l-tetralone (48) are possible acceptors for the prenyl unit. When 2-carboxy-4-hydroxy-l-tetralone (48), or its methyl ester, was introduced into the plant, the prenyl derivatives of 2-carboxy-4-oxotetralone (COT) (43) and 2-car-boxy-4-hydroxy-l-tetralone (50) were isolated as intermediates (Inouye and Leistner, 1988). 

Biological. Catechol is the central metabolite in the bacterial degradation of phenanthrene. Intermediate by-products include l-hydroxy-2-naphthoic acid, 1,2-dihydroxynaphthalene, and salicylic acid (Chapman, 1972 Hou, 1982). It was reported that Beijerinckia, under aerobic conditions, degraded phenanthrene to as-3,4-dihydroxy-3,4-dihydrophenanthracene (Kobayashi and Rittman, 1982). 

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