Quinic and Shikimic Acids

In 1806 Vauquelin isolated from cinchona bark an acidic crystalline substance which he named acide kinique. Later the same substance was reported in the coffee bean, in hay and in various other substances. The ready conversion of quinic acid to aromatic substances early demonstrated its carbocyclic nature. Treatment with aqueous bromine gave protocatechuic acid with phosphorus pentachloride, m-chlorobenzoyl 

The configuration of quinic acid was adduced as LXVII or its mirror image (LXVIIa) as follows  

The carboxyl group must lie on the same side of the plane of the ring as the hydroxyl group at carbon three, otherwise lactone formation between the two groups would be impossible. 

The hydroxyl group attached to carbon one must therefore be trans to that on carbon three. 

The hydroxyl groups on carbon atoms four and five must be cts to each other since they condense with acetone. 

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Optically pure quinic and shikimic acids have been synthesized starting from o-arabinose. The key steps involved treatment of the bis-tosylate (162) with 3 mol of methylenetriphenylphosphorane to give the ylide (163) which with formaldehyde gave the olefin (164) in 82% yield overall. 

More recently, a similar approach was proposed to explain the regioselectivity displayed by Candida antartdca lipase A in the esterification of quinic and shikimic acid derivatives [99]. 

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 present review is to be regarded as a continuation of Fletcher s article1 the facts described therein will not be repeated here unless required for the understanding of recent developments. Because of the considerable expansion of cyclitol chemistry, it is not practicable to cover, as Fletcher did, all compounds of the cyclitol group. Only the inositols, the quercitols, and the inosamines, their derivatives, and some closely related compounds will be discussed the tetrahydroxycyclo-hexanes and -hexenes, and quinic and shikimic acids—on which subjects many important papers have appeared—are not reviewed here.3... 

An example of process optimization by metabolic engineering is the production of intermediates for the synthesis of oseltamivir. This neuraminidase inhibitory drug (Tamiflu ) acts against the common as well as the threatening asian flu. Quinic and shikimic acid can serve as precursors (Scheme 4.20A), but the shiki-... 

The similarity of both quinic and shikimic acid with the target drug is obvious what is perhaps remarkable is just how many steps it takes to get from one to the other. The majority of these steps are concerned with the introduction of the two amino substituents with inversion of stereochemistry at the coloured stereogenic centres. Chiral pool syntheses often have to take long convoluted routes to correct relatively minor errors of structure and stereochemistry. Here this is simply the price we have to pay for a starting material that has the valuable qualities of enantiomeric purity and the right hydrocarbon skeleton. 

The configuration of conduritol, and incidentally those of aZZo-inositol, mwco-inositol, and dihydroconduritol, was elucidated in 1939 by Dangschat and Fischer (6 ), who applied the acetonation-oxidation technique previously used so successfully on quinic and shikimic acids. The steps utilized were as follows ... 

Cranswick A M, Zabkiewicz J A 1979 Quantitative analysis of monosaccharides, cyclitols, sucrose, quinic and shikimic acids in Pinus radiata extracts on a glass support-coated open tubular capillary column by automated gas chromatography. J Chromatogr 171 233-242... 

Grabovskis J, Kreicberga Z 1964 The distribution of quinic and shikimic acids in poplars. Lalvijas PSR Zinatnu Akad Vestis Kim Ser 113-117... 

Plouvier V 1961 Quinic and shikimic acids, bergenine and heterosides in some Hamamelidaceae. CR Acad Sci 252 599-601... 

Figure 2.10, Synthesis of (—)-quinic and (—)-shikimic acid from D-arabinose". Interconversions of (—)-quinic and (—)-shikimic acid ...

Two cyclitolcarboxylic acids occur in Nature quinic and shikimic acid. Structurally they are closely related to each other, shikimic acid being a dehydroquinic acid their interconversion has been achieved by chemical means. The difficult proof of their constitution was obtained by Fischer and Dangschat through several degradative sequences. ... 

Some experiments were done to compare quinic and shikimic acid as carbon sources for pyocyanine biosynthesis in a medium also containing uniformly-labeled glyceroP C and L-alanine- C (MacDonald, 1963). The best incorporation (74%) of the carbon atoms of quinic acid into the carbon atoms of pyocyanine was obtained when quinic acid was added at a concentration of 1 % at the time of inoculation with a small inoculum. If quinic acid was added when pigment formation had just started, or if quinic acid was added at a concentration of 0.25 %, or if a large inoculum of washed cells was used, the incorporation of quinic acid into pyocyanine was less (21— 46 %). The best incorporation (29 or 31 %) of the... 

The investigation of MacDonald (1963) imphcates glycerol, some carbohydrates, and quinic and shikimic acids, which are known to be derived from carbohydrates, as likely precursors of pyocyanine. This study would make it seem unlikely that pyocyanine is derived primarily from amino acids or from the condensation of acetate and malonate units. However, it was not shown that the ring of quinic acid or shikimic acid is incorporated as an intact unit into the ring structure of pyocyanine, and the suggestion that the ring of pyocyanine was ultimately derived from the ring carbon atoms of two molecules of shikimic acid requires further proof. 

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