Dehydroquinic acid derivatives

The simultaneous and selective protection of the two equatorial hydroxyl groups in methyl dihydroquinate [111.1, Scheme 3.111] as the butane-2,3-diace-tal 111.2 was a key strategic feature in a synthesis of inhibitors of 3-dehydroqui-nate synthase. Later in the synthesis, deprotection of intermediate 111.4 required three steps (a) hydrolysis of the trimethylsilyl ether and the butane-2,3-diacetal with trifluoroacetic acid (b) cleavage of the isopropyl phosphonate with bromotrimethylsilane and (c) hydrolysis of the methyl ester with aqueous sodium hydroxide. Compound 111.1 has also been used in the synthesis of inhibitors 3-dehydroquinate dehydratase and influenza neuraminadase - as well as shikimic acid derivatives. ... 

The w-CyN unit described was shown to be incorporated in the biosynthesis of both the ansamycins and also other related antibiotics, such as pactamycin and other compounds [188-190]. With respect to other naturally occurring compounds which contain a partial structure derived from the m-CyN unit in the molecule, asukamycin [191] is a possible shunt metabolite from 3-dehydroquinic acid in the shikimate pathway. Incorporation of [l - 3C]-AHBA (118) into the C-6 methyl group of porfiromycin (120) (a mitomycin group antibiotic) was reported (Fig. 6) [192], and the participation of a m-CyN unit in this biosynthetic pathway and the antibiotics containing a m-CyN unit were reviewed [178,188,190]. 

Dehydroquinic acid, shikimic acid, and chorismic acid are carboxylated compounds containing a six-membered carbocyclic ring with one or two double bonds (Fig. 143). The secondary products derived from these substances either still contain the ring and the C -side chain of the acids (see the structure of the benzoic acid derivatives, of anthranilic and 3-hydroxyanthranilic esters, D 8, D 8.2, D 8.4 and D 8.4.1) or have additional rings (see the formulae of naphthoquinones and anthraquinones, D 8.1, of quinoline, acridine, and benzodiazepine alkaloids, D 8.3.2). The carbon skeletons may be substituted by isoprenoid side chains (see the structure of ubiquinones, D 8.3) and may carry different functional groups, e.g., hydroxy, carboxy, methoxy, and amino groups. 

The first isolable precursor of the aromatic amino acids is dehydroquinic acid, a cyclohexane derivative arising probably from erythrose 4-phosphate and pyruvate. The initial condensation step is similar to the formation of neuraminic acid. By... 

Similarly, the methylene analogue of 3-deoxy-D-arabinoheptulosonic acid 7-phosphate (DAHP) has been prepared from the C7 aldehyde derived from methyl (methyl 3-deoxy-D-arabinoheptulopy-ranosid)onate in 60% yield.The protected 3-dehydroquinate (DHQ) has also been used as starting material in the synthesis of phosphonic DHQ synthase inhibitors by the same methylenediphosphonate approach in 56% yield (Scheme 8.66). Preparation of the phosphonate analogue of porphobilinogen is another illustration of the advantages of this synthetic procedure. ... 

Dehydroquinic, shikimic, and chorismic acids as well as the secondary products derived from these compounds are built in microorganisms and plants. 

Fig. 143. Formation of dehydroquinic, dehydroshikimic, shikimic and chorismic acids and secondary products derived from these compounds...

Simple benzoic acids are synthesized in plants via the shikimate pathway, which is derived from shikimic acid, which is itself derived from quinic acid via 3-dehydroquinic and 3-dehydroshikimic acids (Scheme 68.1). In fact, shikimic, but not quinic, acid has been described in the leaves and stems of this species [14]. The simplest benzoic acids are protocatechuic acid (3,4-dihydroxybenzoic acid) and gallic acid (3,4,5-trihydroxybenzoic acid). The latter proved to be present in the tissues of C. roseus, in addition to vanillic acid (4-hydroxy-3-methoxybenzoic acid) [15]. The quantitative composition of C. roseus in benzoic acids can be seen in Table 68.1, and the structures of these compounds are represented in Fig. 68.1. 

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