Lawsone biosynthesis

McAdam BF, Catella-Lawson F, Mardini lA, Kapoor S, Lawson JA, Fitzgerald GA. Systemic biosynthesis of pros-tacychn by cyclooxygenase (COX)-2 the human... 

The biosynthesis of these anthraquinones parallels those of the menoquinones in bacteria and naphtoquinones of plants for example juglone, vitamin K and lawsone. These compounds are also derived from shikimic (or chorismic) and a-ketoglutaric acids via o-succinylbenzoic acid [5,24]. 1,4-Dihydroxy-2-naphtoic acid is the branching point in the biosynthesis of menoquinones, naphtoquinones and anthraquinones [4],... 

Shihunine.—The diacid (172) is an important intermediate in the biosynthesis of several 1,4-naphthoquinones, viz. lawsone, juglone, and the bacterial mena-... 

The naturally occurring naphthoquinones such as lawsone and juglone are products of the shikimic acid pathway to aromatic amino-acids but the path which leads to these naphthoquinones branches from the main pathway before the formation of aromatic compounds, probably no later than chorismic acid.It will be most interesting to see whether the biosynthesis of shihunine also follows this route all the other bases of plant origin which arise from products of the shikimic acid pathway derive from aromatic precursors. 

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). 

Fig. 6.8. Biosynthesis of juglone and lawsone (modified from Inouye and Leistner, ] Sons, Ltd., Chichester).

During the biosynthesis of these anthraquinones prenylation occurs in a different manner than observed with Rubia, Galium and Morinda (vide supra). The C-2 position (rather than C-3) of the hypothetical naphthalene derivative was prenylated (compare the Catalpa experiments) during the reactions leading to anthraquinones. The pathway to naphthoquinones, however, proceeds via lawsone (2-hydroxy-... 

McAdam, BE, Catella-Lawson, F, Mardini, lA, Kapoor, S, Lawson, JA and FitzGerald, GA (1999) Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2 the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci USA, 96, 272-277. 

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... 

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. 

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