1.4- dihydroxy-2-naphthoate

Kurosu M, Narayanasamy P, Biswas K, Dhiman R, Crick DC (2007) Discovery of 1,4-dihydroxy-2-naphthoate prenyltransferase inhibitors new drug leads for multidrug-resistant Gram-positive pathogens. J Med Chem 50 3973-3975... 

This report deals with the synthesis of rr-tocopherol and plastoquinone-9 from homogentlsate and of phylloquinone from 1,4-dihydroxy-2-naphthoate in chloroplasts. Furthermore, experimental data are presented to support earlier findings on the autonomic role of chloroplast carbon metabolism in forming plastldic Isoprenoids. - The methods applied are described in /5,6,7,8,9/. 

With the bisoxazoline hgand (S)-Phbox and CuCl, the asymmetric oxidative couphng of 2-naphthol and hydroxy-2-naphthoates resulted in an asymmetrically substituted 2,2 -binaphthol with ee s of up to 65% [260]. On the basis of the previous results obtained with this catalyst system, the asymmetric oxidative cross-coupling polymerization of 2,3-dihydroxynaphthalene [261] and methyl 6,6 -dihydroxy-2,2 -binaphthalene-7,7 -dicarboxylate [262] as well as the copolymerization of 6,6 -dihydroxy-2,2 -binaphthalene and dihexyl 6,6 -dihydroxy-2,2 -binaphthalene-7,7 -dicarboxylate with Cu diamine catalysts were carried out imder aerobic conditions, using O2 as the oxidant, and a cross-coupling selectivity of 99% was achieved [263]. 

B. Ethyl l,3-dihydroxy-2-naphthoate. In a 1-1. flask 1 volume (87 ml.) of the crude ester is added in one lot to 3 volumes (261 ml.) of concentrated sulfuric acid without cooling, and the solution is allowed to stand for about 1 week (Note 4). The whole mixture, including any precipitate which may have formed, is poured slowly with stirring into a mixture of 1 kg. of icc and 500 ml. of water (Note 5) the solid yellow ester is filtered with suction, washed with a small amount of cold water, pressed in the filter for 30 minutes with a rubber dam, and finally dried in a vacuum desiccator. The yield of ester melting at 80° is 58-68 g. (50-59%, based on the malonic ester used). 

The yield of ethyl l,3-dihydroxy-2-naphthoate is decreased to 45% if the sulfuric acid solution is allowed to stand for only 2 days. 

Figure 11 Non-o-succinylbenzoate (non-OSB) or futalosine pathway for MK biosynthesis. (4) CHA, chorismate (36) inosine (37) C2 unit, Phosphoenolpyruvate (8) futalosine (38) dehypoxanthinylfutalosine (DHFL) (39) cyclic dehypoxanthinylfutalosine (40) 1,4-dihydroxy-6-naphthoate (2) menaquinone. In the MK structure, n = 9 in Streptomyces and n = 8 in Thermus. , uncertain or not definite.

The authors propose the following mechanism (Scheme 47) The benzoxepine is protonated, yielding the enol. Subsequent proton transfer gives the unstable oxonium ion. Rearrangement via C—O bond cleavage and formation of a new C—C bond generates an aromatic compound, ethyl 3,4-dihydroxy-2-naphthoate. This intermediate then reacts with o-phenylenediamine to yield the respective phenazine. 

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,... 

Fig. 144. Biosynthesis of naphthoquinone and anthraquinone derivatives from chorismic acid 1 2-Succinylbenzoate synthase 2 2-succinylbenzoate Co A ligase, naphthoate synthase 3 l,4-dihydroxy-2-naphtho-ate polyprenyltransferase...

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