Shikimic acid route

You might immediately be struck by the extent of oxygenation in these compounds. The shikimic acid route produced Ar-C3 compounds with at most one OH group in the para position and others... 

Qnnamaldehyde s formation from shikimic add utilizes one of only two biogenetic routes in nature that lead to the aromatized benzene ring (the other pathway is found in the acetogenins and produces secondary metabolites like usnic acid see Experiment [llA]).The shikimic acid route contributes to a class of metabolites called the phenylpropanes (Ph—C3), of which cinnamaldehyde is one of a limited number of simple end products. Another close relative is, for example, eugenol from oil of cloves. 

What kind of experiment would you suggest to decide whether the plant compound eugenin was derived by the polyketide route or the shikimic acid route ... 

P. griseofulvum and P. patulum have many metaboUc products in common and, in addition to griseofulvin, 6-methylsalicylic acid, gentisic acid and patuUn, which are derived from acetate-malonate, a number of related simple phenolic acids, which presumably arise from glucose by the shikimic acid route, have been... 

The shikimate pathway is the major route in the biosynthesis of ubiquinone, menaquinone, phyloquinone, plastoquinone, and various colored naphthoquinones. The early steps of this process are common with the steps involved in the biosynthesis of phenols, flavonoids, and aromatic amino acids. Shikimic acid is formed in several steps from precursors of carbohydrate metabolism. The key intermediate in quinone biosynthesis via the shikimate pathway is the chorismate. In the case of ubiquinones, the chorismate is converted to para-hydoxybenzoate and then, depending on the organism, the process continues with prenylation, decarboxylation, three hydroxy-lations, and three methylation steps. - ... 

The route of formation of the carbazole nucleus is still far from understood, and has been variously considered to arise from 3-prenylquinolone via a pathway involving shikimic acid (394) and mevalonic acid (MVA) (400) (Scheme 3.1) (1,112,362-366), anthranilic acid (397) and prephenic acid (404) via a pathway involving shikimic acid (394) (Scheme 3.2) (367), and also tryptophan (408) involving the mevalonate (400) pathway (Scheme 3.3) (133). All of these pathways lack experimental proof. However, based on the occurrence of the diverse carbazole alkaloids derived from anthranilic acid (397) in the family Rutaceae, the pathway... 

Theoretically, many of the above discrepancies could be settled by experiments with carboxyl-labeled shikimic acid because this functional group would be lost in the formation of phenylalanine, but retained in the case of a direct conversion to gallic acid. Only ambiguous evidence was obtained, however, from such efforts (10), and it was concluded that at least two pathways for gallic acid biosynthesis must exist (14), with the preferential route depending on leaf age and plant species investigated (15,16). 

Coumarins and isocoumarins appear to be of varied origins. Simple coumarins, such as umbelliferone, are formed by the shikimic acid pathway in which hydroxylation of p-hydroxycinnamic acid occurs. Other coumarins, for example alternariol (690), are derived from a polyketide unit, as are a number of chromanones, chromones, pyranones and isocoumarins (B-78MI22400). The biosynthesis of 5-hydroxy-2-methylchromone has been shown to involve the chromanone (60JCS654). However, isocoumarins are also derived from the mixed acetate-shikimate route, through initial cyclization of the polyketide and subsequent lactonization. 

The essential stages of the multistep route used by nature to synthesize aromatic amino acids were elucidated in the 1950s by studies on mutant bacteria (e.g. Aerobacter and Escheridiia coi) the cyclization of D-glucose (17) to 5-dehy-droquinic acid (18) and the formation of shikimic acid (19) [28], The first aromatic compound in the reaction chain is anthranilic acid (20) ... 

Metha, G. et al. Norbornyl Route to Polyoxygenated Cyclohexanes. A Facile Entry into Carbasugars and Shikimic Acid. 3.1 3.3 1998 [153]... 

Fig. 4-2. Simplified reaction route illustrating the formation of lignin precursors. 1, 5-Dehydroquinic acid 2, shikimic acid 3, phenylpyruvic acid 4, phenylalanine 5, cinnamic acid 6, ferulic acid (Ri=H and R2=OCH3), sinapic acid (R,= R2=OCH3), and p-coumaric acid (R1=R2 = H) 7, coniferyl alcohol (Ri = H and R2=OCH3), sinapyl alcohol (Rj = R2=OCH3), and p-coumaryl alcohol (R =R2=H) 8, the corresponding glucosides of 7.

This key intermediate has given its name to Nature s general route to aromatic compounds and many other related six-membeied ring compounds the shikimic acid pathway. This pathway contains some of the most interesting reactions (from a chemist s point of view) in biology. It starts with an aldol reaction between phosphoenol pyruvate as the nucleophilic enol component and the C4 sugar erythrose 4-phosphate as the electrophilic aldehyde. 

The route to shikimic acid in plants involves, as the final steps, the dehydration of dehydro-quinic acid and then reduction of the carbonyl group. Doing the reactions this way round means that the dehydration can be ElcB—much preferred under biological conditions. This is what happens. 

The fatty acid pathway or, as we should call it now, the acyl polymalonate pathway, also gives rise to an inexhaustible variety of aromatic and other compounds belonging to the family of the polyketides. You saw in Chapter 50 how the shikimic acid pathway makes aromatic compounds but the compounds below are from the polyketide route. 

Scheme 10. Possible biosynthetic routes leading from the shikimic acid pathway to betalains and the coexisting flavonoids (excluding anthocyanins) in betalain-bearing members of the Caryophyl-lales.

Jiang, S D, Mekki, B, Singh, G, Wightman, R H, Enantiospecific synthesis of (—)-5-epi-shikimic acid and a new route to (—)-shikimic acid. Tetrahedron Lett., 35, 5505-5508, 1994. 

Seheme4.20 Metabolic engineering route towards the anti-flu drug Oseltamivir (A) and the semi-synthetic cephalosporin Cephalexin (B). Adipoyl-7-ADCAand shikimic acid are produced in recombinant strains of Penicillium chiysogenum and E. coli respectively. 

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