Shikimic acid formation

I, 7-diphosphate.170 1 (f> This tetrose phosphate is involved with phosphoenol pyruvate in the formation of shikimic acid via 3-deoxy-2-keto-D-ara6ino-heptonic acid 7-phosphate and, hence, of aromatic compounds.170(d) A synthesis of the tetrose phosphate has been described.170 1 Aldolase shows a high affinity for the heptulose diphosphate and, compared with that for D-fructose 1,6-diphosphate, the rate of reaction is about 60 %. The enzyme transaldolase, purified 400-fold from yeast, catalyzes the following reversible reaction by transfer of the dihydroxyacetonyl group.l70(o>... 

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). 

The application of radioactive phenolic precursors—quinic acid and shikimic acid (52), phenylalanine (30,53), tyrosine (53), and cinnamic acid (30,31,53)—to infected wheat leaves led to a solvent- and alkali-resistant incorporation of radioactivity into hypersensitively reacting host cells suggesting lignin formation had occurred. 

The synthetic approach used in this work is shown in Scheme 9. Two known solution pathways were used to convert shikimic acid to an epoxide intermediate. In fact, both the (-)35 and the (+)36 enantiomers were formed. After minor synthetic transformations, these epoxides were linked to Ten-tagel S aminomethyl resin with an o-nitrophenyl-derived photocleavable linker 7437 via amide bond formation to give intermediate 75. The first point of variation was added via various iodo-benzyl nitrone carboxylic acids 76 via 1,3-dipolar addition/esterification reactions. Highly constrained resin-bound tetracyclic hydrooxazoles 77 were thereby produced. 

Benzoic acid formation is not the sole pathway in aromatization of quinic and shikimic acids as their administration to rats increases the excretion on urinary catechol [31]. In addition, vanillic acid is also excreted. When rats feed quinic acid mixed in the purified diet, catechol may be readily detected free (unconjugated) as well as... 

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) ... 

According to Robinson (JL), Whittaker and Feany (2), and Rice (3), a great majority of secondary plant products are biosynthesized from acetate and shikimic acid as shown in Figure 1, which describes the formation of 15 groups of natural products. 

Shihunine.—Preliminary results139 indicated that the orchid alkaloid shihunine (153) was derived from (152), an important intermediate in naphthoquinone biosynthesis.140 Further details are now available in a full paper.141 The intact incorporation of (152) is affirmed by the observation that (152), labelled with 13C at C-l, was an efficient and specific precursor for (153). [l-14C]Acetate was examined as a shihunine precursor and was found only to label C-5. This is consistent with the expected formation of (152) from shikimic acid (144) and a-ketoglutarate (151),140 the latter gaining acetate label in its carboxy-groups through the tricarboxylic acid cycle. 

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.

Lipoic acid uses its S-S bond in redox reactions (Chapter 50), while shikimic acid is an intermediate in the formation of compounds with benzene rings, such as phenylalanine, in living things (Chapter 49). Salicylic acid s ethyl ester is aspirin, which is, of course, like the last example ibuprofen, a painkiller. 

We have arrived at prephenic acid, which as its name suggests is the last compound before aromatic compounds are formed, and we may call this the end of the shikimic acid pathway. The final stages of the formation of phenylalanine and tyrosine start with aromatization. Prephenic acid is unstable and loses water and CO2 to form phenylpyruvic acid. This a-keto-acid can be converted into the amino acid by the usual transamination with pyridoxal. 

II. Discovery of the Role of Shikimic Acid in the Formation of Aromatic Compounds. 237... 

Formation of Shikimic Acid in Cell-free Extracts. 245... 

In the presence of unlabeled D-glucose, there was no significant incorporation of labeled acetate, pyruvate, and formate into shikimic acid. Variously labeled D-glucose gave the distribution of activities shown in Fig. 1. Only D-glucose labeled in Cl, C2, equally in C3 and C4, or C6 (abbreviated G-1, G-2, G-3,4, and so on) were available for trial. The large deficiencies which occurred in Cl and C5 of shikimate were, therefore, assigned to G-5. The relative contributions of G-3 and G-4 were unknown, but could be... 

The next stage in the formation of the aromatic amino acids involves the conversion of shikimic acid to prephenic acid (XV) and anthranilic acid (XVI). The conversion of prephenic acid to phenylalanine and t3Tosine, and that of anthranilic acid to tryptophan are fairly well understood and... 

One of the mildest methods for preparing methylene acetals involves reaction of a diol with dimethoxymethane in the presence of a suitable activating agent such as phosphorus pentoxide,176 trimethylsilyl Inflate.177 or lithium bromide and p-toluenesulfonic acid.178 The reaction is also used to make methoxymethyl ethers (see section 4.4,1) from alcohols. Scheme 3,95 illustrates the simultaneous formation of a methoxymethyl ether and a methylene acetal from Shikimic Acid.169 The reaction was adapted to the synthesis of the methylene acetal moiety of the marine antitumour agent Mycalamide B [Scheme 3.96],179... 

Shikimic acid, an intermediate in the biosynthesis of phenazine derivatives (e.g., iodinine, pyocyanin) can act as the sole carbon source in the formation of the phenazine skeleton. 

The quinone ring is derived from isochorismic acid, formed by isomerization of chorismic acid, an intermediate in the shikimic acid pathway for synthesis of the aromatic amino acids. The first intermediate unique to menaquinone formation is o-succinyl benzoate, which is formed by a thitunin pyrophosphate-dependent condensation between 2-oxogluttnate emd chorismic acid. The reaction catalyzed by o-succinylbenzoate synthettise is a complex one, involving initially the formation of the succinic semialdehyde-thiamin diphosphate complex by decarboxylation of 2-oxogluttnate, then addition of the succinyl moiety to isochorismate, followed by removed of the pyruvoyl side chain emd the hydroxyl group of isochorismate. 

Several studies of the biosynthesis of chloramphenicol have led to the conclusion that it is formed via the shikimic acid pathway, specifically from chorismic acid. An arylamine synthetase promotes formation of p-amino-L-phenyl alanine (1 ) 50>51. This product is converted to chloramphenicol (15) by oxidation of the amine function to a nitro group, by hy-droxylation of the benzylic methylene group, reduction of the carboxyl... 

In the meantime, the formation of the main alkaloids in C. ipecacuanha under a variety of conditions has been extensively investigated emetine (1) in callus cultures (49) and under the effects of L-tyrosine supplementation (5t)) emetine (1) and cephaeline (2) in Panamanian ipecac (57), in Nicaraguan ipecac (52), in regenerates obtained by clonal propagation (53,54), in tissue cultures (55) and under the effects of exogenous feeding of shikimic acid and L-phenylalanine (55), in cell suspension and excised root cultures (57), in adventitious root cultures (58), and in callus cultures (56,59) and the effects of age and electrokinetic potential (60) ipecoside (7) in the roots (61) and the effect oi Azotobacter, leaf mold, and farmyard manure on alkaloid content (62). In addition, micropropagation systems for C. ipecacuanha have been developed (63-65). 

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