Shikimic acid isolation

The earliest references to cinnamic acid, cinnamaldehyde, and cinnamyl alcohol are associated with thek isolation and identification as odor-producing constituents in a variety of botanical extracts. It is now generally accepted that the aromatic amino acid L-phenylalanine [63-91-2] a primary end product of the Shikimic Acid Pathway, is the precursor for the biosynthesis of these phenylpropanoids in higher plants (1,2). 

Shikimic acid is isolated from Chinese star anis, Illicium verum, and quinic acid is extracted from the bark of Cinchona trees. Although both compounds can be found in many other plants, their isolation and purification are cumbersome. A fermentation production process of shikimic acid from other renewables such as glucose seems to be successful [46]. 

Draths, K.M. Knop, D.R. Frost, J.W. (1999) Shikimic acid and quinic acid replacing isolation from plant sources with recombinant microbial biocatalysis. J. Am. Chem. Soc., 121, 1603-4. 

This lactone derives from the shikimic acid-cinnamic acid pathway, via oxidative dimerization of coniferyl alcohol. Whereas the presence of yatein itself was not detected in the plants producing steganes, presteganes A and B were isolated in Steganotaenia araliaceae and constitute therefore viable biogenetic precursors [82,83]. 

Among simple unsaturated carbaaldopyranoses, one of the most well-known examples is represented by MK7607, an effective herbicidal substance isolated from the fermentation broth of Corvularia eragrostidis [38]. Preparation of its unnatural antipode 174 was recently accomplished by Singh who exploited (-)-shikimic acid 169 as the chiral source (Scheme 28) [39]. As with quinic acid, the shikimate structure can be... 

Draths, K.M. et al. Shikimic Acid and Quinic Acid Replacing Isolation from Plant Sources with Recombinant Microbial Biocatalysis. 3.3 1999 [116]... 

The main component (80-90%) is (f )-anethole. Star anise oil and (F)-anelhole isolated from it are used in anise liqueur (Anisette, Sambuca) and anise brandy (Pernod, Ouzo, Raki, Arak), liquorice sweets, toothpaste, etc. It has almost completely replaced the original anise seed oil, obtained from the umbellifer P. anisum. Shikimic acid (Wang et al., 2001), used in the production of the antiviral drug Tamiflu (Roche), is extracted from the fruits of Chinese star anise and related species (Rahway, 1989). 

When such strains as E. coli 83-24, which are blocked after shikimic acid, were grown on minimal medium plus aromatic supplement, they accumulated 400-800 mg. of shikimic acid per liter, together with variable amounts of shikimate 5-phosphate. Since no mutants that are blocked between shikimic acid and its phosphorylated form were found, it was considered that the phosphate ester is not on the main path of biosynthesis. As will be pointed out later, enzymic studies showed that shikimate 5-phosphate is actually an intermediate between shikimate and the aromatic compounds. It would appear, therefore, that the block in such strains as E. coli 83-24 is probably immediately after shikimate 5-phosphate. With filtrates from this organism, methods were developed for the isolation of pure shikimate and for its stepwise degradation. ... 

An examination of hydrolysates produced by glycosidase enzyme or pH 3.2 acid treatment of reversed-phase isolates frcm juices of "non-floral " itis vinifera vars. Chardonnay, Sauvignon Blanc and Semilion demonstrated that these grapes contain conjugated forms of monoterpenes, C, norisoprenoids, and shikimic acid-derived metabolites. The volatile conpounds obtained hydrolytically from the conjugates were produced in sufficient concentration to permit ready analysis by GC/MS. The products of pH 3.2 hydrolysis have sensory significance when assessed in a neutral wine. The study further develops the precursor analysis approach as a technique to facilitate research into varietally specific constituents of grapes. 

Figure 1.10 HPLC analysis of organic acids in Cabernet Sauvignon wine using after sample preparation by C18 SPE followed by isolation of organic acids a 500-mg amine-quaternary resin (Figure 1.9). 1. tartaric acid, 2. malic acid, 3. lactic acid, 4. acetic acid, 5. citric acid, 6. pyruvic acid, 7. shikimic acid. Analytical conditions column C18 (250 x 4mm, 5 pun) at room temperature, detection at wavelength 210nm, sample volume injected 20p.L, solvent H3P04 5 x 10 3M with isocradc elution at flow rate 0.6mL/min (Flamini and Dalla Vedova, 1999)...

Davis (184) selected a large number of mutants of Escherichia coli requiring two or more aromatic amino acids for growth, and then tested a large number of substances to see if any could relieve the growth inhibition. Success was attained with shikimic acid (215, 268), at that time a relatively obscure natural product. This indicated either that shikimic acid (structure diagram 1) was a true aromatic precursor or that it could readily be transformed into a true precursor. The likelihood that shikimic acid was a true precursor was increased when other mutants were found to accumulate shikimic acid in the medium, from which it could be isolated (184, 185). 

Davis concluded that shikimic acid was a common precursor of phenylalanine, tyrosine, tryptophan, p-aminobenzoic acid, p-hydroxybenzoic acid, and an unknown sixth factor, and he next set out to determine other substances lying on the biosynthetic pathway. The various mutants were therefore tested for syntrophism, i.e., for the ability of one mutant to produce a substance necessary for the growth of another mutant. There was thus found a thermolabile substance, X, which was a true precursor of shikimic acid (184). X was isolated from culture filtrates and identified as 5-dehydroshikimic acid (744). Similar experiments revealed a substance, W, which was a true precursor of substance X (187, 193). This also was isolated and shown to be 5-dehydroquinic acid (906). The enzyme, named 5-dehydroquinase, converting dehydroquinic acid to dehydroshikimic acid has been partially purified (606). It is fairly stable, has a high specificity, appears to have no cofactors, and is of wide occurrence in bacteria, algae, yeasts, and plants but, as expected, could not be found in mammalian liver. 

The structural and configurational studies of quinic acid (1) by Fischer and Gerda Dangschat were extended during the Basle period to shikimic acid (2), the trihydroxycyclohexenecarboxyhc acid first isolated from the Chinese star anise by Eykman in 1885. This acid was first proved to be a... 

The ulosonic acids participate in many important biological processes. 3-Deoxy-D-ara6/ o-2-heptulosonic acid 7-phosphate (5) is a key intermediate in the biosynthesis of aromatic amino acids in plants and bacteria via shikimic acid pathway [6] and KDO (7) [1,5], DHA (6) [7-10] and KO (8) [4] are key components of the outer membrane of the lipopolysaccharides (LPS) of Gramm-negative bacteria, playing a crucial role in immunospecificity. Similarly act iV-acyl and O-acetyl derivatives of the various isomeric pseudoaminic acids of type 12, isolated from LPS... 

One of the analogues of FK506, rapamycin (sirolimus) produced by Strepto-myces hygroscopicus, is a 31-membered macrocyclic lactone that contains a masked a- and P-diketo amide L-pipecolic acid residue similar to that found in FK506, and a unique triene segment including a distinctive shikimic acid-derived trisubstituted cyclohexane moiety (Fig. 1) [19]. It was originally isolated as an... 

Isomerization in hydrogen fluoride is effective for rearrangement of the readily obtainable triacetate of methyl rflc-4-epishikimate (148b). The methyl ester (149) of rcc-shikimic acid can be isolated ... 

C7H8O5, Mr 172.14, needles, mp. 146-147 °C, [a]p -57° (C2H5OH). D. is isolated as the direct biosynthetic precursor of shikimic acid from culture filtrates of Escherichia coli and is widely distributed in nature. The biosynthesis proceeds through cleavage of water from 3-dehydroquinic acid. 

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