Shikimic acid derivatives

C. Grandjean, G. Angyalosi, E. Loing, E. Adriaenssens, O. Melnyk, V. Pancre, C. Auriault, and H. Gras-Masse, Novel hyperbranched glycomimetics recognized by the human mannose receptor Quinic or shikimic acid derivatives as mannose bioisosteres, ChemBioChem, 2 (2001) 747-757. 

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]. 

Subsequently, Posner published the completely regioselective and highly stereoselective cyclo additions of racemic 3-(p-tolylsulfinyl)-2-pyrone (141) (Scheme 70) with 1,1-dimethoxyethylene [133],vinylether,and vinylthioethers [134]. With the first dienophile, the best diastereoselectivity (an 88 12 ratio of the two endo-adducts) was achieved at room temperature in toluene or hexane as the solvent (48 h). A 10 1 endo/exo mixture of cycloadducts was obtained with vinyl-ether in the presence of ZnBr2 as the catalyst, whereas a total endo selectivity was observed in reactions of 141 with vinylthioethers [134] conducted under high pressures. The bridged bicyclic lactone cycloadducts 142 have been used as versatile synthons in the synthesis of shikimic acid derivatives. Although enantio-merically pure samples of compound 141 could be obtained [134] it was not used as a starting material for asymmetric Diels-Alder reactions (the low yield of (S)-141 precluded this). 

A practical approach to unnatural (+)-shikimic acid derivative 197 (Scheme 32) was proposed by Vandewalle, based on extensive transformation of the desymmetrized building-block 193 [47], The... 

Pericosine B, a secondary metabolite produced by a strain of Periconia bissoides [48], proved to be an interesting target compound due to its significant antitumoral activity. From a structural point of view, pericosine B (201, Scheme 33) can be considered as an unsaturated carbauronic acid or an hydroxylated shikimic acid derivative. 

O-AJkylation of stannylene derivatives of 1,2-diols can be used to introduce members of the trityl ether family onto a secondary alcohol — an otherwise difficult task. In the example shown in Scheme 4.212, a very labile bis- 4-meth-oxyphenyl)(phenyl)methyl ether was installed on a Shikimic Acid derivative.400... 

Benzyl phosphates are less readily attacked by nucleophiles than methyl phosphates and they are more stable towards acidolysis than rm-butyl phosphates Benzyl phosphates are often used in complex polyfunctional targets because they are easily removed by hydrogenolysis. An indication of the reduced reactivity of benzyl phosphates is given in Scheme 7.17.32 Reaction of the phospho-nate diester 17.1 with one equivalent of 1 4-diazabicyclo[2 2 2]octane (DABCO) in refluxing toluene afforded the mono-deprotected derivative 17.2 in quantitative yield. Quinuclidine can also be used as the nucleophile. Assisted cleavage of benzyl phosphates is exemplified by the deprotection of the Shikimic Acid derivative in Scheme 7.18 using bromotrimethylsilane.33 34... 

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. 

Miao FI, Tallarico JA, ffayakawa H, Miinger K, Duffner JL, Koehler AN, Schreiber SL, Lewis TA. Ring-opening and ringclosing reactions of a shikimic acid-derived substrate leading to diverse small molecules. J. Comb. Chem. 2007 9 245-253. 

Another C-C-C-X fragment is shikimic acid-derived 4,5-epoxy-3-hydroxycy-clohex-l-ene-l-carboxylic acid [270]. The latter can be bound onto an amino group which is bound to TentaGel via a Gysen Linker (367) [322]. Subsequent esterification with alkyl or aryl nitrone acids according to Tamura et al. [323] was concurrent with [2 -i- 3]-cycloadditions to the allylic double bond. As a result, tricyclic lactones (370) were obtained, which could readily be modified in many ways to yield a wide variety of polyfunctional structures (Scheme 77). 

The subsequent recognition of glycosides of C13 norisoprenoid compounds and of shikimic acid-derived metabolites as precursors of non-floral grape flavor, was a later development (6). Further aspects of the involvement of glycosides in the flavor of grapes and wines have been recently discussed (7-9). 

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... 

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. ... 

Phenazine-l,6-dicarboxylic acid (167) might appear to be the phenazine formed initially by the coupling of two shikimic acid derivatives, but [2,4- H2]-phenazine-l,6-dicarboxylic acid (as 167) was not incorporated into pyocyanin (173) in Ps. aeruginosa, or iodinin (180) in Brevibacterium iodinum Ps. iodina). ... 

Mention was made above that the nature of the shikimic acid derivatives involved in phenazine ring formation was unknown. In addition, little is known of which atoms of shikimic acid correspond to particular atoms in the phenazine nuclei of the various metabolites a degradation of iodinin after incorporation of [l,6- C2]shikimic acid ° was open to at least two interpretations. 

Shikimic acid derivatives are formally obtained from quinic acid derivatives by dehydration at the C1-C2 position of the cyclohexane. Cinnamoyl shiki-mic acids occur naturally in several plants such as date or mate [20], In addition, they are formed at elevated temperatures from CGAs through loss of water, for example, in coffee roasting. 

Alves C, Barros MT, Maycock CD, Voitura MR (1999) An Efficient Transformation of Quinic Acid to Shikimic Acid Derivatives. Tetrahedron 55 8443... 

Benzene compounds. Benzene compounds are an important group in varietal aroma, abimdant in wines, including aromatic alcohols, aldehydes, volatile phenols and shikimic acid derivates. The volatile phenols in wines can come from grapes, both as free and bound aroma, or be generated during the alcoholic fermentation by chemical reactions such as phenolic add degradation, or in the case of vinylphenols due to brettanomyces contamination (Suarez et al., 2007). Volatile phenols are considered characteristic components of wine aroma, although their influence on the final product may be positive or... 

The volatile fractions of many plants are isolated by steam distillation, distillation, or by solvent extraction (Banthorpe, 1991). The resulting volatile compounds that make up the essence or aroma of plants are called essential oils. Altiiough essential oils are comprised of many types of compounds, monoterpenes are major among them. These oils may also contain metabolically modified fatty acids, aldehydes, hydrocarbons, esters, phenylpropanoid compounds, acetylenic compounds, volatile alcohols, volatile alkaloids, phenylpro-panoids, and other shikimic acid derivatives. 

Two major groups of phenols exist that are formed by the sequential addition of C2 units to a growing chain. Acetyl-CoA is generally used as the primer in fungal systems, whereas a shikimic acid-derived acyl-CoA is required for flavonoid synthesis in higher plants. Flavonoids are multiringed phenols found most commonly in flowers and fruit, where they are responsible for the color. 

The effects of this inhibitor on the metabolism of A. fumigatus were very different from those of the other compounds used, since formation of all the characteristic acetate-derived phenols was strongly suppressed (Packter and Collins, 1974). Treatment of cultures gave a completely altered pattern and led unexpectedly to the secretion of atypical shikimic acid-derived phenols, including 2,3-dihydroxybenzoic acid, 4-hydroxyphenylpyruvic acid, and 4-hydroxybenzyl cyanide. In addition, the inhibitor was metabolized directly by transamination to fluorophenylpyruvic acid. 

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